Lone pair-π interactions in biological systems: occurrence, function, and physical origin.

PubMed

Kozelka, Jiří

2017-12-01

Lone pair-π interactions are now recognized as a supramolecular bond whose existence in biological systems is documented by a growing number of examples. They are commonly attributed to electrostatic forces. This review attempts to highlight some recent discoveries evidencing the important role which lone pair-π interactions, and anion-π interactions in particular, play in stabilizing the structure and affecting the function of biomolecules. Special attention is paid to studies exploring the physical origin of these at first glance counterintuitive interactions between a lone pair of electrons of one residue and the π-cloud of another. Recent theoretical work went beyond the popular electrostatic model and inquired the extent to which orbital interactions have to be taken into account. In at least one biologically relevant case-that of anion-flavin interactions-a substantial charge-transfer component has been shown to operate.

Probing the electrostatics of active site microenvironments along the catalytic cycle for Escherichia coli dihydrofolate reductase.

PubMed

Liu, C Tony; Layfield, Joshua P; Stewart, Robert J; French, Jarrod B; Hanoian, Philip; Asbury, John B; Hammes-Schiffer, Sharon; Benkovic, Stephen J

2014-07-23

Electrostatic interactions play an important role in enzyme catalysis by guiding ligand binding and facilitating chemical reactions. These electrostatic interactions are modulated by conformational changes occurring over the catalytic cycle. Herein, the changes in active site electrostatic microenvironments are examined for all enzyme complexes along the catalytic cycle of Escherichia coli dihydrofolate reductase (ecDHFR) by incorporation of thiocyanate probes at two site-specific locations in the active site. The electrostatics and degree of hydration of the microenvironments surrounding the probes are investigated with spectroscopic techniques and mixed quantum mechanical/molecular mechanical (QM/MM) calculations. Changes in the electrostatic microenvironments along the catalytic environment lead to different nitrile (CN) vibrational stretching frequencies and (13)C NMR chemical shifts. These environmental changes arise from protein conformational rearrangements during catalysis. The QM/MM calculations reproduce the experimentally measured vibrational frequency shifts of the thiocyanate probes across the catalyzed hydride transfer step, which spans the closed and occluded conformations of the enzyme. Analysis of the molecular dynamics trajectories provides insight into the conformational changes occurring between these two states and the resulting changes in classical electrostatics and specific hydrogen-bonding interactions. The electric fields along the CN axes of the probes are decomposed into contributions from specific residues, ligands, and solvent molecules that make up the microenvironments around the probes. Moreover, calculation of the electric field along the hydride donor-acceptor axis, along with decomposition of this field into specific contributions, indicates that the cofactor and substrate, as well as the enzyme, impose a substantial electric field that facilitates hydride transfer. Overall, experimental and theoretical data provide evidence for significant electrostatic changes in the active site microenvironments due to conformational motion occurring over the catalytic cycle of ecDHFR.

Probing the Electrostatics of Active Site Microenvironments along the Catalytic Cycle for Escherichia coli Dihydrofolate Reductase

PubMed Central

2015-01-01

Electrostatic interactions play an important role in enzyme catalysis by guiding ligand binding and facilitating chemical reactions. These electrostatic interactions are modulated by conformational changes occurring over the catalytic cycle. Herein, the changes in active site electrostatic microenvironments are examined for all enzyme complexes along the catalytic cycle of Escherichia coli dihydrofolate reductase (ecDHFR) by incorporation of thiocyanate probes at two site-specific locations in the active site. The electrostatics and degree of hydration of the microenvironments surrounding the probes are investigated with spectroscopic techniques and mixed quantum mechanical/molecular mechanical (QM/MM) calculations. Changes in the electrostatic microenvironments along the catalytic environment lead to different nitrile (CN) vibrational stretching frequencies and 13C NMR chemical shifts. These environmental changes arise from protein conformational rearrangements during catalysis. The QM/MM calculations reproduce the experimentally measured vibrational frequency shifts of the thiocyanate probes across the catalyzed hydride transfer step, which spans the closed and occluded conformations of the enzyme. Analysis of the molecular dynamics trajectories provides insight into the conformational changes occurring between these two states and the resulting changes in classical electrostatics and specific hydrogen-bonding interactions. The electric fields along the CN axes of the probes are decomposed into contributions from specific residues, ligands, and solvent molecules that make up the microenvironments around the probes. Moreover, calculation of the electric field along the hydride donor–acceptor axis, along with decomposition of this field into specific contributions, indicates that the cofactor and substrate, as well as the enzyme, impose a substantial electric field that facilitates hydride transfer. Overall, experimental and theoretical data provide evidence for significant electrostatic changes in the active site microenvironments due to conformational motion occurring over the catalytic cycle of ecDHFR. PMID:24977791

Quantifying protein microstructure and electrostatic effects on the change in Gibbs free energy of binding in immobilized metal affinity chromatography.

PubMed

Pathange, Lakshmi P; Bevan, David R; Zhang, Chenming

2008-03-01

Electrostatic forces play a major role in maintaining both structural and functional properties of proteins. A major component of protein electrostatics is the interactions between the charged or titratable amino acid residues (e.g., Glu, Lys, and His), whose pK(a) (or the change of the pK(a)) value could be used to study protein electrostatics. Here, we report the study of electrostatic forces through experiments using a well-controlled model protein (T4 lysozyme) and its variants. We generated 10 T4 lysozyme variants, in which the electrostatic environment of the histidine residue was perturbed by altering charged and neutral amino acid residues at various distances from the histidine (probe) residue. The electrostatic perturbations were theoretically quantified by calculating the change in free energy (DeltaDeltaG(E)) using Coulomb's law. On the other hand, immobilized metal affinity chromatography (IMAC) was used to quantify these perturbations in terms of protein binding strength or change in free energy of binding (DeltaDeltaG(B)), which varies from -0.53 to 0.99 kcal/mol. For most of the variants, there is a good correlation (R(2) = 0.97) between the theoretical DeltaDeltaG(E) and experimental DeltaDeltaG(B) values. However, there are three deviant variants, whose histidine residue was found to be involved in site-specific interactions (e.g., ion pair and steric hindrance), which were further investigated by molecular dynamics simulation. This report demonstrates that the electrostatic (DeltaDeltaG(Elec)) and microstructural effects (DeltaDeltaG(Micro)) in a protein can be quantified by IMAC through surface histidine mediated protein-metal ion interaction and that the unique microstructure around a histidine residue can be identified by identifying the abnormal binding behaviors during IMAC.

Effect of polarization on the stability of a helix dimer

NASA Astrophysics Data System (ADS)

Wang, Xing Y.; Zhang, John Z. H.

2011-01-01

Molecular dynamics (MD) simulations have been carried out to study helix-helix interaction using both standard AMBER and polarized force fields. Comparison of the two simulations shows that electrostatic polarization of intra-protein hydrogen bonds plays a significant role in stabilizing the structure of helix dimer. This stabilizing effect is clearly demonstrated by examining the monomer structure, helix crossing angle and stability of backbone hydrogen bonds under AMBER and PPC. Since reliable prediction of protein-protein structure is a significant challenge, the current study should help shed light on the importance of electrostatic polarization of protein in helix-helix interaction and helix bundle structures.

Evidence that electrostatic interactions between vesicle-associated membrane protein 2 and acidic phospholipids may modulate the fusion of transport vesicles with the plasma membrane.

PubMed

Williams, Dumaine; Vicôgne, Jérome; Zaitseva, Irina; McLaughlin, Stuart; Pessin, Jeffrey E

2009-12-01

The juxtamembrane domain of vesicle-associated membrane protein (VAMP) 2 (also known as synaptobrevin2) contains a conserved cluster of basic/hydrophobic residues that may play an important role in membrane fusion. Our measurements on peptides corresponding to this domain determine the electrostatic and hydrophobic energies by which this domain of VAMP2 could bind to the adjacent lipid bilayer in an insulin granule or other transport vesicle. Mutation of residues within the juxtamembrane domain that reduce the VAMP2 net positive charge, and thus its interaction with membranes, inhibits secretion of insulin granules in beta cells. Increasing salt concentration in permeabilized cells, which reduces electrostatic interactions, also results in an inhibition of insulin secretion. Similarly, amphipathic weak bases (e.g., sphingosine) that reverse the negative electrostatic surface potential of a bilayer reverse membrane binding of the positively charged juxtamembrane domain of a reconstituted VAMP2 protein and inhibit membrane fusion. We propose a model in which the positively charged VAMP and syntaxin juxtamembrane regions facilitate fusion by bridging the negatively charged vesicle and plasma membrane leaflets.

The role of positively charged amino acids and electrostatic interactions in the complex of U1A protein and U1 hairpin II RNA

PubMed Central

Law, Michael J.; Linde, Michael E.; Chambers, Eric J.; Oubridge, Chris; Katsamba, Phinikoula S.; Nilsson, Lennart; Haworth, Ian S.; Laird-Offringa, Ite A.

2006-01-01

Previous kinetic investigations of the N-terminal RNA recognition motif (RRM) domain of spliceosomal protein U1A, interacting with its RNA target U1 hairpin II, provided experimental evidence for a ‘lure and lock’ model of binding in which electrostatic interactions first guide the RNA to the protein, and close range interactions then lock the two molecules together. To further investigate the ‘lure’ step, here we examined the electrostatic roles of two sets of positively charged amino acids in U1A that do not make hydrogen bonds to the RNA: Lys20, Lys22 and Lys23 close to the RNA-binding site, and Arg7, Lys60 and Arg70, located on ‘top’ of the RRM domain, away from the RNA. Surface plasmon resonance-based kinetic studies, supplemented with salt dependence experiments and molecular dynamics simulation, indicate that Lys20 predominantly plays a role in association, while nearby residues Lys22 and Lys23 appear to be at least as important for complex stability. In contrast, kinetic analyses of residues away from the RNA indicate that they have a minimal effect on association and stability. Thus, well-positioned positively charged residues can be important for both initial complex formation and complex maintenance, illustrating the multiple roles of electrostatic interactions in protein–RNA complexes. PMID:16407334

Electrostatic effects on hyaluronic acid configuration

NASA Astrophysics Data System (ADS)

Berezney, John; Saleh, Omar

2015-03-01

In systems of polyelectrolytes, such as solutions of charged biopolymers, the electrostatic repulsion between charged monomers plays a dominant role in determining the molecular conformation. Altering the ionic strength of the solvent thus affects the structure of such a polymer. Capturing this electrostatically-driven structural dependence is important for understanding many biological systems. Here, we use single molecule manipulation experiments to collect force-extension behavior on hyaluronic acid (HA), a polyanion which is a major component of the extracellular matrix in all vertebrates. By measuring HA elasticity in a variety of salt conditions, we are able to directly assess the contribution of electrostatics to the chain's self-avoidance and local stiffness. Similar to recent results from our group on single-stranded nucleic acids, our data indicate that HA behaves as a swollen chain of electrostatic blobs, with blob size proportional to the solution Debye length. Our data indicate that the chain structure within the blob is not worm-like, likely due to long-range electrostatic interactions. We discuss potential models of this effect.

Interactions between charged nanoparticles and giant vesicles fabricated from inverted-headgroup lipids

NASA Astrophysics Data System (ADS)

Wang, Lu; Malmstadt, Noah

2017-10-01

The surface chemistry of the cell membrane plays an important role in how cells interact with particulate species. These interactions are dictated in large part by lipid headgroup charge. To investigate the nature of electrostatic interactions between lipid bilayers and nanoparticles in solution, we studied nanoparticles interacting with the zwitterionic lipid 1,2-dioleoyl-glycero-3-phosphocholine (DOPC), and its inverted-headgroup analog DOCP. These interactions were investigated by fabricating giant unilamellar vesicles (GUVs) with DOPC lipids and DOCP lipids respectively, and introducing nanoparticles to suspensions of both. GUVs displayed various deformational modes depending on the charge and size of the nanoparticles as well as the compositions of the GUVs. The differences in the responses of the two lipid species illuminate how the phosphate and choline groups on the lipid interact with charged nanoparticles. This study suggests that the phosphate group dominates the lipid-nanoparticle electrostatic interaction. We speculate that the formation of water clathrate structures around the choline group inhibits interactions between negatively charged nanoparticles and the positively charged choline.

Electrostatically Tuned Self-Assembly of Branched Amphiphilic Peptides

DOE PAGES

Ting, Christina L.; Frischknecht, Amalie L.; Stevens, Mark J.; ...

2014-06-19

Electrostatics plays an important role in the self-assembly of amphiphilic peptides. To develop a molecular understanding of the role of the electrostatic interactions, we develop a coarse-grained model peptide and apply self-consistent field theory to investigate the peptide assembly into a variety of aggregate nanostructures. We find that the presence and distribution of charged groups on the hydrophilic branches of the peptide can modify the molecular configuration from extended to collapsed. This change in molecular configuration influences the packing into spherical micelles, cylindrical micelles (nanofibers), or planar bilayers. The effects of charge distribution therefore has important implications for the designmore » and utility of functional materials based on peptides.« less

Electrostatic Similarity Analysis of Human β-Defensin Binding in the Melanocortin System

PubMed Central

Nix, Matthew A.; Kaelin, Christopher B.; Palomino, Rafael; Miller, Jillian L.; Barsh, Gregory S.; Millhauser, Glenn L.

2015-01-01

Summary The β-defensins are a class of small cationic proteins that serve as components of numerous systems in vertebrate biology, including the immune and melanocortin systems. Human β-defensin 3 (HBD3), which is produced in the skin, has been found to bind to melanocortin receptors 1 and 4 through complementary electrostatics, a unique mechanism of ligand-receptor interaction. This finding indicates that electrostatics alone, and not specific amino acid contact points, could be sufficient for function in this ligand-receptor system, and further suggests that other small peptide ligands could interact with these receptors in a similar fashion. Here, we conducted molecular-similarity analyses and functional studies of additional members of the human β-defensin family, examining their potential as ligands of melanocortin-1 receptor, through selection based on their electrostatic similarity to HBD3. Using Poisson-Boltzmann electrostatic calculations and molecular-similarity analysis, we identified members of the human β-defensin family that are both similar and dissimilar to HBD3 in terms of electrostatic potential. Synthesis and functional testing of a subset of these β-defensins showed that peptides with an HBD3-like electrostatic character bound to melanocortin receptors with high affinity, whereas those that were anticorrelated to HBD3 showed no binding affinity. These findings expand on the central role of electrostatics in the control of this ligand-receptor system and further demonstrate the utility of employing molecular-similarity analysis. Additionally, we identified several new potential ligands of melanocortin-1 receptor, which may have implications for our understanding of the role defensins play in melanocortin physiology. PMID:26536271

Particle-In-Cell Simulations of the Solar Wind Interaction with Lunar Crustal Magnetic Anomalies: Magnetic Cusp Regions

NASA Technical Reports Server (NTRS)

Poppe, A. R.; Halekas, J. S.; Delory, G. T.; Farrell, W. M.

2012-01-01

As the solar wind is incident upon the lunar surface, it will occasionally encounter lunar crustal remanent magnetic fields. These magnetic fields are small-scale, highly non-dipolar, have strengths up to hundreds of nanotesla, and typically interact with the solar wind in a kinetic fashion. Simulations, theoretical analyses, and spacecraft observations have shown that crustal fields can reflect solar wind protons via a combination of magnetic and electrostatic reflection; however, analyses of surface properties have suggested that protons may still access the lunar surface in the cusp regions of crustal magnetic fields. In this first report from a planned series of studies, we use a 1 1/2-dimensional, electrostatic particle-in-cell code to model the self-consistent interaction between the solar wind, the cusp regions of lunar crustal remanent magnetic fields, and the lunar surface. We describe the self-consistent electrostatic environment within crustal cusp regions and discuss the implications of this work for the role that crustal fields may play regulating space weathering of the lunar surface via proton bombardment.

Probing lipid membrane electrostatics

NASA Astrophysics Data System (ADS)

Yang, Yi

The electrostatic properties of lipid bilayer membranes play a significant role in many biological processes. Atomic force microscopy (AFM) is highly sensitive to membrane surface potential in electrolyte solutions. With fully characterized probe tips, AFM can perform quantitative electrostatic analysis of lipid membranes. Electrostatic interactions between Silicon nitride probes and supported zwitterionic dioleoylphosphatidylcholine (DOPC) bilayer with a variable fraction of anionic dioleoylphosphatidylserine (DOPS) were measured by AFM. Classical Gouy-Chapman theory was used to model the membrane electrostatics. The nonlinear Poisson-Boltzmann equation was numerically solved with finite element method to provide the potential distribution around the AFM tips. Theoretical tip-sample electrostatic interactions were calculated with the surface integral of both Maxwell and osmotic stress tensors on tip surface. The measured forces were interpreted with theoretical forces and the resulting surface charge densities of the membrane surfaces were in quantitative agreement with the Gouy-Chapman-Stern model of membrane charge regulation. It was demonstrated that the AFM can quantitatively detect membrane surface potential at a separation of several screening lengths, and that the AFM probe only perturbs the membrane surface potential by <2%. One important application of this technique is to estimate the dipole density of lipid membrane. Electrostatic analysis of DOPC lipid bilayers with the AFM reveals a repulsive force between the negatively charged probe tips and the zwitterionic lipid bilayers. This unexpected interaction has been analyzed quantitatively to reveal that the repulsion is due to a weak external field created by the internai membrane dipole moment. The analysis yields a dipole moment of 1.5 Debye per lipid with a dipole potential of +275 mV for supported DOPC membranes. This new ability to quantitatively measure the membrane dipole density in a noninvasive manner will be useful in identifying the biological effects of the dipole potential. Finally, heterogeneous model membranes were studied with fluid electric force microscopy (FEFM). Electrostatic mapping was demonstrated with 50 nm resolution. The capabilities of quantitative electrostatic measurement and lateral charge density mapping make AFM a unique and powerful probe of membrane electrostatics.

Fluorescence studies on binding of pyrene and its derivatives to humic acid

NASA Astrophysics Data System (ADS)

Nakashima, K.; Maki, M.; Ishikawa, F.; Yoshikawa, T.; Gong, Y.-K.; Miyajima, T.

2007-07-01

Binding of pyrene (PyH) and its derivatives to humic acid (HA) has been studied by fluorescence spectroscopy. The nature of the interaction between HA and pyrene derivatives are extensively investigated by employing three derivatives ranging from anionic to cationic compounds: 1-pyrenebutylic acid (PyA), 1-pyrenemethanol (PyM), and 1-pyrenebutyltrimethylammonium bromide (PyB). Binding constants between HA and PyX (X = H, A, M, B) are obtained by steady-state fluorescence quenching techniques, and it is found that PyB has a markedly large binding constant among the pyrene family. This is attributed to a strong electrostatic interaction between cationic PyB and anionic HA. The result suggests that an electrostatic interaction plays a dominant role in binding of pyrenes to humic acid. The importance of electrostatic interaction was also confirmed by a salt effect on the binding constant. Influence of collisional quenching on the binding constant, which causes overestimation of the binding constant, was examined by time-resolved fluorescence spectroscopy as well as temperature effect in steady-state fluorescence measurements. It is elucidated that collisional quenching does not much bring overestimation into the binding constants.

Role of a highly conserved electrostatic interaction on the surface of cytochrome C in control of the redox function.

PubMed

Tai, Hulin; Mikami, Shin-ichi; Irie, Kiyofumi; Watanabe, Naoki; Shinohara, Naoya; Yamamoto, Yasuhiko

2010-01-12

In Hydrogenobacter thermophilus cytochrome c(552), an electrostatic interaction between Lys8 and Glu68 in the N- and C-terminal helices, respectively, stabilizes its protein structure [Travaglini-Allocatelli, C., Gianni, S., Dubey, V. K., Borgia, A., Di Matteo, A., Bonivento, D., Cutruzzola, F., Bren, K. L., and Brunori, M. (2005) J. Biol. Chem. 280, 25729-25734], this electrostatic interaction being a highly conserved structural feature of the cytochrome c family. In the present study, the functional consequences of removal of the interaction through replacement of Lys8 by Ala have been investigated in order to elucidate the molecular mechanisms responsible for functional control of the protein. The mutation resulted in a decrease in protein stability, as reflected in lowering of the denaturation temperature by approximately 2-9 degrees C, and a negative shift by approximately 8 mV of the redox potential (E(m)) of the protein. The decrease in the protein stability was attributed to the enthalpic loss due to the removal of the intramolecular interaction. The negative shift of the E(m) value was shown to be due to the effect of the mutation on the entropic contribution to the E(m) value. The small, but subtle, effects of removal of the conserved electrostatic interaction, occurring at approximately 1.4 nm away from heme iron, on the thermodynamic properties of the protein demonstrated not only that the interaction is important for maintaining the functional properties of the protein but also that amino acid residues relatively remote from the heme active site play sizable roles in functional control of the protein.

A Study on the Effect of Surface Lysine to Arginine Mutagenesis on Protein Stability and Structure Using Green Fluorescent Protein

PubMed Central

Sokalingam, Sriram; Raghunathan, Govindan; Soundrarajan, Nagasundarapandian; Lee, Sun-Gu

2012-01-01

Two positively charged basic amino acids, arginine and lysine, are mostly exposed to protein surface, and play important roles in protein stability by forming electrostatic interactions. In particular, the guanidinium group of arginine allows interactions in three possible directions, which enables arginine to form a larger number of electrostatic interactions compared to lysine. The higher pKa of the basic residue in arginine may also generate more stable ionic interactions than lysine. This paper reports an investigation whether the advantageous properties of arginine over lysine can be utilized to enhance protein stability. A variant of green fluorescent protein (GFP) was created by mutating the maximum possible number of lysine residues on the surface to arginines while retaining the activity. When the stability of the variant was examined under a range of denaturing conditions, the variant was relatively more stable compared to control GFP in the presence of chemical denaturants such as urea, alkaline pH and ionic detergents, but the thermal stability of the protein was not changed. The modeled structure of the variant indicated putative new salt bridges and hydrogen bond interactions that help improve the rigidity of the protein against different chemical denaturants. Structural analyses of the electrostatic interactions also confirmed that the geometric properties of the guanidinium group in arginine had such effects. On the other hand, the altered electrostatic interactions induced by the mutagenesis of surface lysines to arginines adversely affected protein folding, which decreased the productivity of the functional form of the variant. These results suggest that the surface lysine mutagenesis to arginines can be considered one of the parameters in protein stability engineering. PMID:22792305

Electrostatic roles in electron transfer from [NiFe] hydrogenase to cytochrome c3 from Desulfovibrio vulgaris Miyazaki F.

PubMed

Sugimoto, Yu; Kitazumi, Yuki; Shirai, Osamu; Nishikawa, Koji; Higuchi, Yoshiki; Yamamoto, Masahiro; Kano, Kenji

2017-05-01

Electrostatic interactions between proteins are key factors that govern the association and reaction rate. We spectroscopically determine the second-order reaction rate constant (k) of electron transfer from [NiFe] hydrogenase (H 2 ase) to cytochrome (cyt) c 3 at various ionic strengths (I). The k value decreases with I. To analyze the results, we develop a semi-analytical formula for I dependence of k based on the assumptions that molecules are spherical and the reaction proceeds via a transition state. Fitting of the formula to the experimental data reveals that the interaction occurs in limited regions with opposite charges and with radii much smaller than those estimated from crystal structures. This suggests that local charges in H 2 ase and cyt c 3 play important roles in the reaction. Although the crystallographic data indicate a positive electrostatic potential over almost the entire surface of the proteins, there exists a small region with negative potential on H 2 ase at which the electron transfer from H 2 ase to cyt c 3 may occur. This local negative potential region is identical to the hypothetical interaction sphere predicted by the analysis. Furthermore, I dependence of k is predicted by the Adaptive Poisson-Boltzmann Solver considering all charges of the amino acids in the proteins and the configuration of H 2 ase/cyt c 3 complex. The calculation reproduces the experimental results except at extremely low I. These results indicate that the stabilization derived from the local electrostatic interaction in the H 2 ase/cyt c 3 complex overcomes the destabilization derived from the electrostatic repulsion of the overall positive charge of both proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of short range hydrophobic interactions and long range electrostatic forces on the aggregation kinetics of a monoclonal antibody and a dual-variable domain immunoglobulin at low and high concentrations.

PubMed

Kumar, Vineet; Dixit, Nitin; Zhou, Liqiang Lisa; Fraunhofer, Wolfgang

2011-12-12

The purpose of this work was to determine the nature of long and short-range forces governing protein aggregation kinetics at low and high concentrations for a monoclonal antibody (IgG1) and a dual-variable-domain immunoglobulin (DVD-Ig). Protein-protein interactions (PPI) were studied under dilute conditions by utilizing the methods of static (B(22)) and dynamic light scattering (k(D)). PPI in solutions containing minimal ionic strengths were characterized to get detailed insights into the impact of ionic strength on aggregation. Microcalorimetry and susceptibility to denature at air-liquid interface were used to assess the tertiary structure and quiescent stability studies were conducted to study aggregation characteristics. Results for IgG1 showed that electrostatic interactions governed protein aggregation kinetics both under dilute and concentrated conditions (i.e., 5 mg/mL and 150 mg/mL). For DVD-Ig molecules, on the other hand, although electrostatic interactions governed protein aggregation under dilute conditions, hydrophobic forces clearly determined the kinetics at high concentrations. This manuscript shows for the first time that short-range hydrophobic interactions can outweigh electrostatic forces and play an important role in determining protein aggregation at high concentrations. Additionally, results show that although higher-order virial coefficients become significant under low ionic strength conditions, removal of added charges may be used to enhance the aggregation stability of dilute protein formulations. Copyright © 2011 Elsevier B.V. All rights reserved.

Stimulation and inhibition of enzymatic hydrolysis by organosolv lignins as determined by zeta potential and hydrophobicity

Treesearch

Yang Huang; Shaolong Sun; Chen Huang; Qiang Yong; Thomas Elder; Maobing Tu

2017-01-01

Background: Lignin typically inhibits enzymatic hydrolysis of cellulosic biomass, but certain organosolv lignins or lignosulfonates enhance enzymatic hydrolysis. The hydrophobic and electrostatic interactions between lignin and cellulases play critical roles in the enzymatic hydrolysis process. However, how to incorporate these two...

Spectral studies of N-nonyl acridine orange in anionic, cationic and neutral surfactants

NASA Astrophysics Data System (ADS)

Wiosetek-Reske, Agnieszka M.; Wysocki, Stanisław

2006-08-01

The spectroscopic and photophysical properties of N-nonyl acridine orange - a metachromatic dye useful as a mitochondrial probe in living cells - are reported in water and microheterogeneous media: anionic sodium dodecylsulfate (SDS), cationic cetyltrimethylammonium bromide (CTAB) and neutral octylophenylpolyoxyethylene ether (TX-100). The spectral changes of N-nonyl acridine orange were observed in the presence of varying amount of SDS, CTAB and TX-100 and indicated formation of a dye-surfactant complex. The spectral changes were also regarded to be caused by the incorporation of dye molecules to micelles. It was proved by calculated values Kb and f in the following order: Kb TX-100 > Kb CTAB > Kb SDS and fTX-100 > fCTAB > fSDS. NAO binds to the micelle regardless the micellar charge. There are two types of interactions between NAO and micelles: hydrophobic and electrostatic. The hydrophobic interactions play a dominant role in binding of the dye to neutral TX-100. The unexpected fact of the binding NAO to cationic CTAB can be explained by a dominant role of hydrophobic interactions over electrostatic repulsion. Therefore, the affinity of NAO to CTAB is smaller than TX-100. Electrostatic interactions play an important role in binding of NAO to anionic micelles SDS. We observed a prolonged fluorescence lifetime after formation of the dye-surfactant complex τSDS > τTX-100 > τCTAB > τwater, the dye being protected against water in this environment. TX-100 is found to stabilize the excited state of NAO which is more polar than the ground state. Spectroscopic and photophysical properties of NAO will be helpful for a better understanding of the nature of binding and distribution inside mammalian cells.

Exploring the inter-molecular interactions in amyloid-β protofibril with molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area free energy calculations.

PubMed

Liu, Fu-Feng; Liu, Zhen; Bai, Shu; Dong, Xiao-Yan; Sun, Yan

2012-04-14

Aggregation of amyloid-β (Aβ) peptides correlates with the pathology of Alzheimer's disease. However, the inter-molecular interactions between Aβ protofibril remain elusive. Herein, molecular mechanics Poisson-Boltzmann surface area analysis based on all-atom molecular dynamics simulations was performed to study the inter-molecular interactions in Aβ(17-42) protofibril. It is found that the nonpolar interactions are the important forces to stabilize the Aβ(17-42) protofibril, while electrostatic interactions play a minor role. Through free energy decomposition, 18 residues of the Aβ(17-42) are identified to provide interaction energy lower than -2.5 kcal/mol. The nonpolar interactions are mainly provided by the main chain of the peptide and the side chains of nine hydrophobic residues (Leu17, Phe19, Phe20, Leu32, Leu34, Met35, Val36, Val40, and Ile41). However, the electrostatic interactions are mainly supplied by the main chains of six hydrophobic residues (Phe19, Phe20, Val24, Met35, Val36, and Val40) and the side chains of the charged residues (Glu22, Asp23, and Lys28). In the electrostatic interactions, the overwhelming majority of hydrogen bonds involve the main chains of Aβ as well as the guanidinium group of the charged side chain of Lys28. The work has thus elucidated the molecular mechanism of the inter-molecular interactions between Aβ monomers in Aβ(17-42) protofibril, and the findings are considered critical for exploring effective agents for the inhibition of Aβ aggregation.

Exploring the inter-molecular interactions in amyloid-β protofibril with molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area free energy calculations

NASA Astrophysics Data System (ADS)

Liu, Fu-Feng; Liu, Zhen; Bai, Shu; Dong, Xiao-Yan; Sun, Yan

2012-04-01

Aggregation of amyloid-β (Aβ) peptides correlates with the pathology of Alzheimer's disease. However, the inter-molecular interactions between Aβ protofibril remain elusive. Herein, molecular mechanics Poisson-Boltzmann surface area analysis based on all-atom molecular dynamics simulations was performed to study the inter-molecular interactions in Aβ17-42 protofibril. It is found that the nonpolar interactions are the important forces to stabilize the Aβ17-42 protofibril, while electrostatic interactions play a minor role. Through free energy decomposition, 18 residues of the Aβ17-42 are identified to provide interaction energy lower than -2.5 kcal/mol. The nonpolar interactions are mainly provided by the main chain of the peptide and the side chains of nine hydrophobic residues (Leu17, Phe19, Phe20, Leu32, Leu34, Met35, Val36, Val40, and Ile41). However, the electrostatic interactions are mainly supplied by the main chains of six hydrophobic residues (Phe19, Phe20, Val24, Met35, Val36, and Val40) and the side chains of the charged residues (Glu22, Asp23, and Lys28). In the electrostatic interactions, the overwhelming majority of hydrogen bonds involve the main chains of Aβ as well as the guanidinium group of the charged side chain of Lys28. The work has thus elucidated the molecular mechanism of the inter-molecular interactions between Aβ monomers in Aβ17-42 protofibril, and the findings are considered critical for exploring effective agents for the inhibition of Aβ aggregation.

A theoretical study of complexes formed between cations and curved aromatic systems: electrostatics does not always control cation-π interaction.

PubMed

Carrazana-García, Jorge A; Cabaleiro-Lago, Enrique M; Rodríguez-Otero, Jesús

2017-04-19

The present work studies the interaction of two extended curved π-systems (corannulene and sumanene) with various cations (sodium, potassium, ammonium, tetramethylammonium, guanidinium and imidazolium). Polyatomic cations are models of groups found in important biomolecules in which cation-π interaction plays a fundamental role. The results indicate an important size effect: with extended π systems and cations of the size of potassium and larger, dispersion is much more important than has been generally recognized for cation-π interactions. In most of the systems studied here, the stability of the cation-π complexes is the result of a balanced combination of electrostatic, induction and dispersion contributions. None of the systems studied here owes its stability to the electrostatic interaction more than 42%. Induction dominates stabilization in complexes with sodium, and in some of the potassium and ammonium complexes. In complexes with large cations and with flat cations dispersion is the major stabilizing contribution and can provide more than 50% of the stabilization energy. This implies that theoretical studies of the cation-π interaction involving large or even medium-size fragments require a level of calculation capable of properly modelling dispersion. The separation between the cation and the π system is another important factor to take into account, especially when the fragments of the cation-π complex are bound (for example, to a protein backbone) and cannot interact at the most favourable distance.

Electrostatically Biased Binding of Kinesin to Microtubules

PubMed Central

Zheng, Wenjun; Alonso, Maria; Huber, Gary; Dlugosz, Maciej; McCammon, J. Andrew; Cross, Robert A.

2011-01-01

The minimum motor domain of kinesin-1 is a single head. Recent evidence suggests that such minimal motor domains generate force by a biased binding mechanism, in which they preferentially select binding sites on the microtubule that lie ahead in the progress direction of the motor. A specific molecular mechanism for biased binding has, however, so far been lacking. Here we use atomistic Brownian dynamics simulations combined with experimental mutagenesis to show that incoming kinesin heads undergo electrostatically guided diffusion-to-capture by microtubules, and that this produces directionally biased binding. Kinesin-1 heads are initially rotated by the electrostatic field so that their tubulin-binding sites face inwards, and then steered towards a plus-endwards binding site. In tethered kinesin dimers, this bias is amplified. A 3-residue sequence (RAK) in kinesin helix alpha-6 is predicted to be important for electrostatic guidance. Real-world mutagenesis of this sequence powerfully influences kinesin-driven microtubule sliding, with one mutant producing a 5-fold acceleration over wild type. We conclude that electrostatic interactions play an important role in the kinesin stepping mechanism, by biasing the diffusional association of kinesin with microtubules. PMID:22140358

Electrostatic potential calculation for biomolecules--creating a database of pre-calculated values reported on a per residue basis for all PDB protein structures.

PubMed

Rocchia, W; Neshich, G

2007-10-05

STING and Java Protein Dossier provide a collection of physical-chemical parameters, describing protein structure, stability, function, and interaction, considered one of the most comprehensive among the available protein databases of similar type. Particular attention in STING is paid to the electrostatic potential. It makes use of DelPhi, a well-known tool that calculates this physical-chemical quantity for biomolecules by solving the Poisson Boltzmann equation. In this paper, we describe a modification to the DelPhi program aimed at integrating it within the STING environment. We also outline how the "amino acid electrostatic potential" and the "surface amino acid electrostatic potential" are calculated (over all Protein Data Bank (PDB) content) and how the corresponding values are made searchable in STING_DB. In addition, we show that the STING and Java Protein Dossier are also capable of providing these particular parameter values for the analysis of protein structures modeled in computers or being experimentally solved, but not yet deposited in the PDB. Furthermore, we compare the calculated electrostatic potential values obtained by using the earlier version of DelPhi and those by STING, for the biologically relevant case of lysozyme-antibody interaction. Finally, we describe the STING capacity to make queries (at both residue and atomic levels) across the whole PDB, by looking at a specific case where the electrostatic potential parameter plays a crucial role in terms of a particular protein function, such as ligand binding. BlueStar STING is available at http://www.cbi.cnptia.embrapa.br.

Crystal Field in Rare-Earth Complexes: From Electrostatics to Bonding.

PubMed

Alessandri, Riccardo; Zulfikri, Habiburrahman; Autschbach, Jochen; Bolvin, Hélène

2018-04-11

The flexibility of first-principles (ab initio) calculations with the SO-CASSCF (complete active space self-consistent field theory with a treatment of the spin-orbit (SO) coupling by state interaction) method is used to quantify the electrostatic and covalent contributions to crystal field parameters. Two types of systems are chosen for illustration: 1) The ionic and experimentally well-characterized PrCl 3 crystal; this study permits a revisitation of the partition of contributions proposed in the early days of crystal field theory; and 2) a series of sandwich molecules [Ln(η n -C n H n ) 2 ] q , with Ln=Dy, Ho, Er, and Tm and n=5, 6, and 8, in which the interaction between Ln III and the aromatic ligands is more difficult to describe within an electrostatic approach. It is shown that a model with three layers of charges reproduces the electrostatic field generated by the ligands and that the covalency plays a qualitative role. The one-electron character of crystal field theory is discussed and shown to be valuable, although it is not completely quantitative. This permits a reduction of the many-electron problem to a discussion of the energy of the seven 4f orbitals. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Contemporary NMR Studies of Protein Electrostatics.

PubMed

Hass, Mathias A S; Mulder, Frans A A

2015-01-01

Electrostatics play an important role in many aspects of protein chemistry. However, the accurate determination of side chain proton affinity in proteins by experiment and theory remains challenging. In recent years the field of nuclear magnetic resonance spectroscopy has advanced the way that protonation states are measured, allowing researchers to examine electrostatic interactions at an unprecedented level of detail and accuracy. Experiments are now in place that follow pH-dependent (13)C and (15)N chemical shifts as spatially close as possible to the sites of protonation, allowing all titratable amino acid side chains to be probed sequence specifically. The strong and telling response of carefully selected reporter nuclei allows individual titration events to be monitored. At the same time, improved frameworks allow researchers to model multiple coupled protonation equilibria and to identify the underlying pH-dependent contributions to the chemical shifts.

Modeling the Electrostatics of Hollow Shell Suspensions: Ion Distribution, Pair Interactions, and Many-Body Effects.

PubMed

Hallez, Yannick; Meireles, Martine

2016-10-11

Electrostatic interactions play a key role in hollow shell suspensions as they determine their structure, stability, thermodynamics, and rheology and also the loading capacity of small charged species for nanoreservoir applications. In this work, fast, reliable modeling strategies aimed at predicting the electrostatics of hollow shells for one, two, and many colloids are proposed and validated. The electrostatic potential inside and outside a hollow shell with a finite thickness and a specific permittivity is determined analytically in the Debye-Hückel (DH) limit. An expression for the interaction potential between two such hollow shells is then derived and validated numerically. It follows a classical Yukawa form with an effective charge depending on the shell geometry, permittivity, and inner and outer surface charge densities. The predictions of the Ornstein-Zernike (OZ) equation with this pair potential to determine equations of state are then evaluated by comparison to results obtained with a Brownian dynamics algorithm coupled to the resolution of the linearized Poisson-Boltzmann and Laplace equations (PB-BD simulations). The OZ equation based on the DLVO-like potential performs very well in the dilute regime as expected, but also quite well, and more surprisingly, in the concentrated regime in which full spheres exhibit significant many-body effects. These effects are shown to vanish for shells with small thickness and high permittivity. For highly charged hollow shells, we propose and validate a charge renormalization procedure. Finally, using PB-BD simulations, we show that the cell model predicts the ion distribution inside and outside hollow shells accurately in both electrostatically dilute and concentrated suspensions. We then determine the shell loading capacity as a function of salt concentration, volume fraction, and surface charge density for nanoreservoir applications such as drug delivery, sensing, or smart coatings.

Complex coacervates as a foundation for synthetic underwater adhesives

PubMed Central

Stewart, Russell J.; Wang, Ching Shuen; Shao, Hui

2011-01-01

Complex coacervation was proposed to play a role in the formation of the underwater bioadhesive of the Sandcastle worm (Phragmatopoma californica) based on the polyacidic and polybasic nature of the glue proteins and the balance of opposite charges at physiological pH. Morphological studies of the secretory system suggested the natural process does not involve complex coacervation as commonly defined. The distinction may not be important because electrostatic interactions likely play an important role in formation of the sandcastle glue. Complex coacervation has also been invoked in the formation of adhesive underwater silk fibers of caddisfly larvae and the adhesive plaques of mussels. A process similar to complex coacervation, that is, condensation and dehydration of biopolyelectrolytes through electrostatic associations, seems plausible for the caddisfly silk. This much is clear, the sandcastle glue complex coacervation model provided a valuable blueprint for the synthesis of a biomimetic, waterborne, underwater adhesive with demonstrated potential for repair of wet tissue. PMID:21081223

The origins of the directionality of noncovalent intermolecular interactions.

PubMed

Wang, Changwei; Guan, Liangyu; Danovich, David; Shaik, Sason; Mo, Yirong

2016-01-05

The recent σ-hole concept emphasizes the contribution of electrostatic attraction to noncovalent bonds, and implies that the electrostatic force has an angular dependency. Here a set of clusters, which includes hydrogen bonding, halogen bonding, chalcogen bonding, and pnicogen bonding systems, is investigated to probe the magnitude of covalency and its contribution to the directionality in noncovalent bonding. The study is based on the block-localized wavefunction (BLW) method that decomposes the binding energy into the steric and the charge transfer (CT) (hyperconjugation) contributions. One unique feature of the BLW method is its capability to derive optimal geometries with only steric effect taken into account, while excluding the CT interaction. The results reveal that the overall steric energy exhibits angular dependency notably in halogen bonding, chalcogen bonding, and pnicogen bonding systems. Turning on the CT interactions further shortens the intermolecular distances. This bond shortening enhances the Pauli repulsion, which in turn offsets the electrostatic attraction, such that in the final sum, the contribution of the steric effect to bonding is diminished, leaving the CT to dominate the binding energy. In several other systems particularly hydrogen bonding systems, the steric effect nevertheless still plays the major role whereas the CT interaction is minor. However, in all cases, the CT exhibits strong directionality, suggesting that the linearity or near linearity of noncovalent bonds is largely governed by the charge-transfer interaction whose magnitude determines the covalency in noncovalent bonds. © 2015 Wiley Periodicals, Inc.

Albumin adsorption on CoCrMo alloy surfaces

NASA Astrophysics Data System (ADS)

Yan, Yu; Yang, Hongjuan; Su, Yanjing; Qiao, Lijie

2015-12-01

Proteins can adsorb on the surface of artificial joints immediately after being implanted. Although research studying protein adsorption on medical material surfaces has been carried out, the mechanism of the proteins’ adsorption which affects the corrosion behaviour of such materials still lacks in situ observation at the micro level. The adsorption of bovine serum albumin (BSA) on CoCrMo alloy surfaces was studied in situ by AFM and SKPFM as a function of pH and the charge of CoCrMo alloy surfaces. Results showed that when the specimens were uncharged, hydrophobic interaction could govern the process of the adsorption rather than electrostatic interaction, and BSA molecules tended to adsorb on the surfaces forming a monolayer in the side-on model. Results also showed that adsorbed BSA molecules could promote the corrosion process for CoCrMo alloys. When the surface was positively charged, the electrostatic interaction played a leading role in the adsorption process. The maximum adsorption occurred at the isoelectric point (pH 4.7) of BSA.

Adrenodoxin supports reactions catalyzed by microsomal steroidogenic cytochrome P450s

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pechurskaya, Tatiana A.; Harnastai, Ivan N.; Grabovec, Irina P.

2007-02-16

The interaction of adrenodoxin (Adx) and NADPH cytochrome P450 reductase (CPR) with human microsomal steroidogenic cytochrome P450s was studied. It is found that Adx, mitochondrial electron transfer protein, is able to support reactions catalyzed by human microsomal P450s: full length CYP17, truncated CYP17, and truncated CYP21. CPR, but not Adx, supports activity of truncated CYP19. Truncated and the full length CYP17s show distinct preference for electron donor proteins. Truncated CYP17 has higher activity with Adx compared to CPR. The alteration in preference to electron donor does not change product profile for truncated enzymes. The electrostatic contacts play a major rolemore » in the interaction of truncated CYP17 with either CPR or Adx. Similarly electrostatic contacts are predominant in the interaction of full length CYP17 with Adx. We speculate that Adx might serve as an alternative electron donor for CYP17 at the conditions of CPR deficiency in human.« less

Robust cross-links in molluscan adhesive gels: Testing for contributions from hydrophobic and electrostatic interactions

PubMed Central

Smith, A.M.; Robinson, T. M.; Salt, M. D.; Hamilton, K. S.; Silvia, B. E.; Blasiak, R.

2009-01-01

The cross-linking interactions that provide cohesive strength to molluscan adhesive gels were investigated. Metal-based interactions have been shown to play an important role in the glue of the slug Arion subfuscus (Draparnaud), but other types of interactions may also contribute to the glue's strength and their role has not been investigated. This study shows that treatments that normally disrupt hydrophobic or electrostatic interactions have little to no effect on the slug glue. High salt concentrations and non-ionic detergent do not affect the solubility of the proteins in the glue or the ability of the glue proteins to stiffen gels. In contrast, metal chelation markedly disrupts the gel. Experiments with gel filtration chromatography identify a 40 kDa protein that is a central component of the cross-links in the glue. This 40 kDa protein forms robust macromolecular aggregations that are stable even in the presence of high concentrations of salt, non-ionic detergent, urea or metal chelators. Metal chelation during glue secretion, however, may block some of these cross-links. Such robust, non-specific interactions in an aqueous environment are highly unusual for hydrogels and reflect an intriguing cross-linking mechanism. PMID:18952190

Robust cross-links in molluscan adhesive gels: testing for contributions from hydrophobic and electrostatic interactions.

PubMed

Smith, A M; Robinson, T M; Salt, M D; Hamilton, K S; Silvia, B E; Blasiak, R

2009-02-01

The cross-linking interactions that provide cohesive strength to molluscan adhesive gels were investigated. Metal-based interactions have been shown to play an important role in the glue of the slug Arion subfuscus (Draparnaud), but other types of interactions may also contribute to the glue's strength and their role has not been investigated. This study shows that treatments that normally disrupt hydrophobic or electrostatic interactions have little to no effect on the slug glue. High salt concentrations and non-ionic detergent do not affect the solubility of the proteins in the glue or the ability of the glue proteins to stiffen gels. In contrast, metal chelation markedly disrupts the gel. Experiments with gel filtration chromatography identify a 40 kDa protein that is a central component of the cross-links in the glue. This 40 kDa protein forms robust macromolecular aggregations that are stable even in the presence of high concentrations of salt, non-ionic detergent, urea or metal chelators. Metal chelation during glue secretion, however, may block some of these cross-links. Such robust, non-specific interactions in an aqueous environment are highly unusual for hydrogels and reflect an intriguing cross-linking mechanism.

Some physicochemical aspects of water-soluble mineral flotation.

PubMed

Wu, Zhijian; Wang, Xuming; Liu, Haining; Zhang, Huifang; Miller, Jan D

2016-09-01

Some physicochemical aspects of water-soluble mineral flotation including hydration phenomena, associations and interactions between collectors, air bubbles, and water-soluble mineral particles are presented. Flotation carried out in saturated salt solutions, and a wide range of collector concentrations for effective flotation of different salts are two basic aspects of water-soluble mineral flotation. Hydration of salt ions, mineral particle surfaces, collector molecules or ions, and collector aggregates play an important role in water-soluble mineral flotation. The adsorption of collectors onto bubble surfaces is suggested to be the precondition for the association of mineral particles with bubbles. The association of collectors with water-soluble minerals is a complicated process, which may include the adsorption of collector molecules or ions onto such surfaces, and/or the attachment of collector precipitates or crystals onto the mineral surfaces. The interactions between the collectors and the minerals include electrostatic and hydrophobic interactions, hydrogen bonding, and specific interactions, with electrostatic and hydrophobic interactions being the common mechanisms. For the association of ionic collectors with minerals with an opposite charge, electrostatic and hydrophobic interactions could have a synergistic effect, with the hydrophobic interactions between the hydrophobic groups of the previously associated collectors and the hydrophobic groups of oncoming collectors being an important attractive force. Association between solid particles and air bubbles is the key to froth flotation, which is affected by hydrophobicity of the mineral particle surfaces, surface charges of mineral particles and bubbles, mineral particle size and shape, temperature, bubble size, etc. The use of a collector together with a frother and the use of mixed surfactants as collectors are suggested to improve flotation. Copyright © 2016 Elsevier B.V. All rights reserved.

Intracellular Membrane Association of the Aplysia cAMP Phosphodiesterase Long and Short Forms via Different Targeting Mechanisms*

PubMed Central

Kim, Kun-Hyung; Jun, Yong-Woo; Park, Yongsoo; Lee, Jin-A; Suh, Byung-Chang; Lim, Chae-Seok; Lee, Yong-Seok; Kaang, Bong-Kiun; Jang, Deok-Jin

2014-01-01

Phosphodiesterases (PDEs) play key roles in cAMP compartmentalization, which is required for intracellular signaling processes, through specific subcellular targeting. Previously, we showed that the long and short forms of Aplysia PDE4 (ApPDE4), which are localized to the membranes of distinct subcellular organelles, play key roles in 5-hydroxytryptamine-induced synaptic facilitation in Aplysia sensory and motor synapses. However, the molecular mechanism of the isoform-specific distinct membrane targeting was not clear. In this study, we further investigated the molecular mechanism of the membrane targeting of the ApPDE4 long and short forms. We found that the membrane targeting of the long form was mediated by hydrophobic interactions, mainly via 16 amino acids at the N-terminal region, whereas the short form was targeted solely to the plasma membrane, mainly by nonspecific electrostatic interactions between their N termini and the negatively charged lipids such as the phosphatidylinositol polyphosphates PI4P and PI(4,5)P2, which are embedded in the inner leaflet of the plasma membrane. Moreover, oligomerization of the long or short form by interaction of their respective upstream conserved region domains, UCR1 and UCR2, enhanced their plasma membrane targeting. These results suggest that the long and short forms of ApPDE4 are distinctly targeted to intracellular membranes through their direct association with the membranes via hydrophobic and electrostatic interactions, respectively. PMID:25077971

Interaction of Human Hemoglobin with Methotrexate

NASA Astrophysics Data System (ADS)

Zaharia, M.; Gradinaru, R.

2015-05-01

This study focuses on the interaction between methotrexate and human hemoglobin using steady-state ultraviolet-visible and fluorescence quenching methods. Fluorescence quenching was found to be valuable in assessing drug binding to hemoglobin. The quenching of methotrexate is slightly smaller than the quenching observed with related analogs (dihydrofolate and tetrahydrofolate). The quenching studies were performed at four different temperatures and various pH values. The number of binding sites for tryptophan is ~1. Parameter-dependent assays revealed that electrostatic forces play an essential role in the methotrexate-hemoglobin interaction. Furthermore, the complex was easily eluted using gel filtration chromatography.

Electrostatic interactions play an essential role in the binding of oleic acid with α-lactalbumin in the HAMLET-like complex: a study using charge-specific chemical modifications.

PubMed

Xie, Yongjing; Min, Soyoung; Harte, Níal P; Kirk, Hannah; O'Brien, John E; Voorheis, H Paul; Svanborg, Catharina; Hun Mok, K

2013-01-01

Human α-lactalbumin made lethal to tumor cells (HAMLET) and its analogs are partially unfolded protein-oleic acid (OA) complexes that exhibit selective tumoricidal activity normally absent in the native protein itself. To understand the nature of the interaction between protein and OA moieties, charge-specific chemical modifications of lysine side chains involving citraconylation, acetylation, and guanidination were employed and the biophysical and biological properties were probed. Upon converting the original positively-charged lysine residues to negatively-charged citraconyl or neutral acetyl groups, the binding of OA to protein was eliminated, as were any cytotoxic activities towards osteosarcoma cells. Retention of the positive charges by converting lysine residues to homoarginine groups (guanidination); however, yielded unchanged binding of OA to protein and identical tumoricidal activity to that displayed by the wild-type α-lactalbumin-oleic acid complex. With the addition of OA, the wild-type and guanidinated α-lactalbumin proteins underwent substantial conformational changes, such as partial unfolding, loss of tertiary structure, but retention of secondary structure. In contrast, no significant conformational changes were observed in the citraconylated and acetylated α-lactalbumins, most likely because of the absence of OA binding. These results suggest that electrostatic interactions between the positively-charged basic groups on α-lactalbumin and the negatively-charged carboxylate groups on OA molecules play an essential role in the binding of OA to α-lactalbumin and that these interactions appear to be as important as hydrophobic interactions. Copyright © 2012 Wiley Periodicals, Inc.

Quantum-mechanical analysis of the energetic contributions to π stacking in nucleic acids versus rise, twist, and slide.

PubMed

Parker, Trent M; Hohenstein, Edward G; Parrish, Robert M; Hud, Nicholas V; Sherrill, C David

2013-01-30

Symmetry-adapted perturbation theory (SAPT) is applied to pairs of hydrogen-bonded nucleobases to obtain the energetic components of base stacking (electrostatic, exchange-repulsion, induction/polarization, and London dispersion interactions) and how they vary as a function of the helical parameters Rise, Twist, and Slide. Computed average values of Rise and Twist agree well with experimental data for B-form DNA from the Nucleic Acids Database, even though the model computations omitted the backbone atoms (suggesting that the backbone in B-form DNA is compatible with having the bases adopt their ideal stacking geometries). London dispersion forces are the most important attractive component in base stacking, followed by electrostatic interactions. At values of Rise typical of those in DNA (3.36 Å), the electrostatic contribution is nearly always attractive, providing further evidence for the importance of charge-penetration effects in π-π interactions (a term neglected in classical force fields). Comparison of the computed stacking energies with those from model complexes made of the "parent" nucleobases purine and 2-pyrimidone indicates that chemical substituents in DNA and RNA account for 20-40% of the base-stacking energy. A lack of correspondence between the SAPT results and experiment for Slide in RNA base-pair steps suggests that the backbone plays a larger role in determining stacking geometries in RNA than in B-form DNA. In comparisons of base-pair steps with thymine versus uracil, the thymine methyl group tends to enhance the strength of the stacking interaction through a combination of dispersion and electrosatic interactions.

On the binding of indeno[1,2-c]isoquinolines in the DNA-topoisomerase I cleavage complex.

PubMed

Xiao, Xiangshu; Antony, Smitha; Pommier, Yves; Cushman, Mark

2005-05-05

An ab initio quantum mechanics calculation is reported which predicts the orientation of indenoisoquinoline 4 in the ternary cleavage complex formed from DNA and topoisomerase I (top1). The results of this calculation are consistent with the hypothetical structures previously proposed for the indenoisoquinoline-DNA-top1 ternary complexes based on molecular modeling, the crystal structure of a recently reported ternary complex, and the biological results obtained with a pair of diaminoalkyl-substituted indenoisoquinoline enantiomers. The results of these studies indicate that the pi-pi stacking interactions between the indenoisoquinolines and the neighboring DNA base pairs play a major role in determining binding orientation. The calculation of the electrostatic potential surface maps of the indenoisoquinolines and the adjacent DNA base pairs shows electrostatic complementarity in the observed binding orientation, leading to the conclusion that electrostatic attraction between the intercalators and the base pairs in the cleavage complex plays a major stabilizing role. On the other hand, the calculation of LUMO and HOMO energies of indenoisoquinoline 13b and neighboring DNA base pairs in conjunction with NBO analysis indicates that charge transfer complex formation plays a relatively minor role in stabilizing the ternary complexes derived from indenoisoquinolines, DNA, and top1. The results of these studies are important in understanding the existing structure-activity relationships for the indenoisoquinolines as top1 inhibitors and as anticancer agents, and they will be important in the future design of indenoisoquinoline-based top1 inhibitors.

Transferability of polarizable models for ion-water electrostatic interaction

NASA Astrophysics Data System (ADS)

Masia, Marco

2009-06-01

Studies of ion-water systems at condensed phase and at interfaces have pointed out that molecular and ionic polarization plays an important role for many phenomena ranging from hydrogen bond dynamics to water interfaces' structure. Classical and ab initio Molecular Dynamics simulations reveal that induced dipole moments at interfaces (e.g. air-water and water-protein) are usually high, hinting that polarizable models to be implemented in classical force fields should be very accurate in reproducing the electrostatic properties of the system. In this paper the electrostatic properties of three classical polarizable models for ion-water interaction are compared with ab initio results both at gas and condensed phase. For Li+- water and Cl--water dimers the reproducibility of total dipole moments obtained with high level quantum chemical calculations is studied; for the same ions in liquid water, Car-Parrinello Molecular Dynamics simulations are used to compute the time evolution of ionic and molecular dipole moments, which are compared with the classical models. The PD2-H2O model developed by the author and coworkers [Masia et al. J. Chem. Phys. 2004, 121, 7362] together with the gaussian intermolecular damping for ion-water interaction [Masia et al. J. Chem. Phys. 2005, 123, 164505] showed to be the fittest in reproducing the ab initio results from gas to condensed phase, allowing for force field transferability.

Electrostatic interactions during acidic phospholipid reactivation of DnaA protein, the Escherichia coli initiator of chromosomal replication.

PubMed

Kitchen, J L; Li, Z; Crooke, E

1999-05-11

The initiation of Escherichia coli chromosomal replication by DnaA protein is strongly influenced by the tight binding of the nucleotides ATP and ADP. Anionic phospholipids in a fluid bilayer promote the conversion of inactive ADP-DnaA protein to replicatively active ATP-DnaA protein in vitro, and thus likely play a key role in regulating DnaA activity. Previous studies have revealed that, during this reactivation, a specific region of DnaA protein inserts into the hydrophobic portion of the lipid bilayer in an acidic phospholipid-dependent manner. To elucidate the requirement for acidic phospholipids in the reactivation process, the contribution of electrostatic forces in the interaction of DnaA and lipid was examined. DnaA-lipid binding required anionic phospholipids, and DnaA-lipid binding as well as lipid-mediated release of DnaA-bound nucleotide were inhibited by increased ionic strength, suggesting the involvement of electrostatic interactions in these processes. As the vesicular content of acidic phospholipids was increased, both nucleotide release and DnaA-lipid binding increased in a linear, parallel manner. Given that DnaA-membrane binding, the insertion of DnaA into the membrane, and the consequent nucleotide release all require anionic phospholipids, the acidic headgroup may be necessary to recruit DnaA protein to the membrane for insertion and subsequent reactivation for replication.

Encapsulation of cisplatin as an anti-cancer drug into boron-nitride and carbon nanotubes: Molecular simulation and free energy calculation.

PubMed

Roosta, Sara; Hashemianzadeh, Seyed Majid; Ketabi, Sepideh

2016-10-01

Encapsulation of cisplatin anticancer drug into the single walled (10, 0) carbon nanotube and (10, 0) boron-nitride nanotube was investigated by quantum mechanical calculations and Monte Carlo Simulation in aqueous solution. Solvation free energies and complexation free energies of the cisplatin@ carbon nanotube and cisplatin@ boron-nitride nanotube complexes was determined as well as radial distribution functions of entitled compounds. Solvation free energies of cisplatin@ carbon nanotube and cisplatin@ boron-nitride nanotube were -4.128kcalmol(-1) and -2457.124kcalmol(-1) respectively. The results showed that cisplatin@ boron-nitride nanotube was more soluble species in water. In addition electrostatic contribution of the interaction of boron- nitride nanotube complex and solvent was -281.937kcalmol(-1) which really more than Van der Waals and so the electrostatic interactions play a distinctive role in the solvation free energies of boron- nitride nanotube compounds. On the other hand electrostatic part of the interaction of carbon nanotube complex and solvent were almost the same as Van der Waals contribution. Complexation free energies were also computed to study the stability of related structures and the free energies were negative (-374.082 and -245.766kcalmol(-1)) which confirmed encapsulation of drug into abovementioned nanotubes. However, boron-nitride nanotubes were more appropriate for encapsulation due to their larger solubility in aqueous solution. Copyright © 2016 Elsevier B.V. All rights reserved.

Ionic strength independence of charge distributions in solvation of biomolecules

NASA Astrophysics Data System (ADS)

Virtanen, J. J.; Sosnick, T. R.; Freed, K. F.

2014-12-01

Electrostatic forces enormously impact the structure, interactions, and function of biomolecules. We perform all-atom molecular dynamics simulations for 5 proteins and 5 RNAs to determine the dependence on ionic strength of the ion and water charge distributions surrounding the biomolecules, as well as the contributions of ions to the electrostatic free energy of interaction between the biomolecule and the surrounding salt solution (for a total of 40 different biomolecule/solvent combinations). Although water provides the dominant contribution to the charge density distribution and to the electrostatic potential even in 1M NaCl solutions, the contributions of water molecules and of ions to the total electrostatic interaction free energy with the solvated biomolecule are comparable. The electrostatic biomolecule/solvent interaction energies and the total charge distribution exhibit a remarkable insensitivity to salt concentrations over a huge range of salt concentrations (20 mM to 1M NaCl). The electrostatic potentials near the biomolecule's surface obtained from the MD simulations differ markedly, as expected, from the potentials predicted by continuum dielectric models, even though the total electrostatic interaction free energies are within 11% of each other.

Turbulent particulate transportation during electrostatic precipitation

NASA Astrophysics Data System (ADS)

Choi, Bum Seog

The generation of secondary flows and turbulence by a corona discharge influences particle transport in an electrostatic precipitator (ESP), and is known to play an important role in the particle collection process. However, it is difficult to characterise theoretically and experimentally the ``turbulent'' fluctuations of the gas flow produced by negative tuft corona. Because of this difficulty, only limited studies have been undertaken previously to understand the structure of corona-induced turbulence and its influence on particle transport in ESPs. The present study is aimed at modelling electrohydrodynamic turbulent flows and particle transport, and at establishing an unproved understanding of them. For a multiply interactive coupling of electrostatics, fluid dynamics and particle dynamics, a strongly coupled system of the governing equations has been solved. The present computer model has considered the most important interaction mechanisms including an ionic wind, corona- induced turbulence and the particle space charge effect. Numerical simulations have been performed for the extensive validation of the numerical and physical models. To account for electrically excited turbulence associated with the inhomogeneous and unsteady characteristics of negative corona discharges, a new turbulence model (called the electrostatic turbulence model) has been developed. In this, an additional production or destruction term is included into the turbulent kinetic energy and dissipation rate equations. It employs a gradient type model of the current density and an electrostatic diffusivity concept. The results of the computation show that the electrostatic turbulence model gives much better agreement with the experimental data than the conventional RNG k-ɛ turbulence model when predicting turbulent gas flows and particle distributions in an ESP. Computations of turbulent particulate two-phase flows for both mono-dispersed and poly-dispersed particles have been performed. The effects of coriona-induced turbulence and the particle space charge on particle transport and the collection process have been investigated. The calculated results for the poly-dispersed particulate flow were compared with those of the mono-dispersed particulate flow, and significant differences were demonstrated. It is established that effective particle- particle interaction occurs, due to the influence of the particle space charge, even for dilute gas-particle flows that occur in ESPs.

Role of non-native electrostatic interactions in the coupled folding and binding of PUMA with Mcl-1

PubMed Central

Chu, Wen-Ting; Clarke, Jane; Shammas, Sarah L.; Wang, Jin

2017-01-01

PUMA, which belongs to the BH3-only protein family, is an intrinsically disordered protein (IDP). It binds to its cellular partner Mcl-1 through its BH3 motif, which folds upon binding into an α helix. We have applied a structure-based coarse-grained model, with an explicit Debye—Hückel charge model, to probe the importance of electrostatic interactions both in the early and the later stages of this model coupled folding and binding process. This model was carefully calibrated with the experimental data on helical content and affinity, and shown to be consistent with previously published experimental data on binding rate changes with respect to ionic strength. We find that intramolecular electrostatic interactions influence the unbound states of PUMA only marginally. Our results further suggest that intermolecular electrostatic interactions, and in particular non-native electrostatic interactions, are involved in formation of the initial encounter complex. We are able to reveal the binding mechanism in more detail than is possible using experimental data alone however, and in particular we uncover the role of non-native electrostatic interactions. We highlight the potential importance of such electrostatic interactions for describing the binding reactions of IDPs. Such approaches could be used to provide predictions for the results of mutational studies. PMID:28369057

Insight into π-hole interactions containing the inorganic heterocyclic compounds S2N2/SN2P2.

PubMed

Lu, Bo; Zhang, Xueying; Meng, Lingpeng; Zeng, Yanli

2017-08-01

Similar to σ-hole interactions, the π-hole interaction has attracted much attention in recent years. According to the positive electrostatic potentials above and below the surface of inorganic heterocyclic compounds S 2 N 2 and three SN 2 P 2 isomers (heterocyclic compounds 1-4), and the negative electrostatic potential outside the X atom of XH 3 (X = N, P, As), S 2 N 2 /SN 2 P 2 ⋯XH 3 (X = N, P, As) complexes were constructed and optimized at the MP2/aug-cc-pVTZ level. The X atom of XH 3 (X = N, P, As) is almost perpendicular to the ring of the heterocyclic compounds. The π-hole interaction energy becomes greater as the trend goes from 1⋯XH 3 to 4⋯XH 3 . These π-hole interactions are weak and belong to "closed-shell" noncovalent interactions. According to the energy decomposition analysis, of the three attractive terms, the dispersion energy contributes more than the electrostatic energy. The polarization effect also plays an important role in the formation of π-hole complexes, with the contrasting phenomena of decreasing electronic density in the π-hole region and increasing electric density outside the X atom of XH 3 (X = N, P, As). Graphical abstract Computed density difference plots for the complexes 3⋯NH 3 (a 1 ), 3⋯PH 3 (b 1 ), 3⋯AsH 3 (c 1 ) and electron density shifts for the complexes 3⋯NH 3 (a 2 ), 3⋯PH 3 (b 2 ),3⋯AsH 3 (c 2 ) on the 0.001 a.u. contour.

Molecular interactions and residues involved in force generation in the T4 viral DNA packaging motor.

PubMed

Migliori, Amy D; Smith, Douglas E; Arya, Gaurav

2014-12-12

Many viruses utilize molecular motors to package their genomes into preformed capsids. A striking feature of these motors is their ability to generate large forces to drive DNA translocation against entropic, electrostatic, and bending forces resisting DNA confinement. A model based on recently resolved structures of the bacteriophage T4 motor protein gp17 suggests that this motor generates large forces by undergoing a conformational change from an extended to a compact state. This transition is proposed to be driven by electrostatic interactions between complementarily charged residues across the interface between the N- and C-terminal domains of gp17. Here we use atomistic molecular dynamics simulations to investigate in detail the molecular interactions and residues involved in such a compaction transition of gp17. We find that although electrostatic interactions between charged residues contribute significantly to the overall free energy change of compaction, interactions mediated by the uncharged residues are equally if not more important. We identify five charged residues and six uncharged residues at the interface that play a dominant role in the compaction transition and also reveal salt bridging, van der Waals, and solvent hydrogen-bonding interactions mediated by these residues in stabilizing the compact form of gp17. The formation of a salt bridge between Glu309 and Arg494 is found to be particularly crucial, consistent with experiments showing complete abrogation in packaging upon Glu309Lys mutation. The computed contributions of several other residues are also found to correlate well with single-molecule measurements of impairments in DNA translocation activity caused by site-directed mutations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Electrostatic Charging and Particle Interactions in Microscopic Insulating Grains

NASA Astrophysics Data System (ADS)

Lee, Victor

In this thesis, we experimentally investigate the electrostatic charging as well as the particle interactions in microscopic insulating grains. First, by tracking individual grains accelerated in an electric field, we quantitatively demonstrate that tribocharging of same-material grains depends on particle size. Large grains tend to charge positively, and small ones tend to charge negatively. Theories based on the transfer of trapped electrons can explain this tendency but have not been validated. Here we show that the number of trapped electrons, measured independently by a thermoluminescence technique, is orders of magnitude too small to be responsible for the amount of charge transferred. This result reveals that trapped electrons are not responsible for same-material tribocharging of dielectric particles. Second, same-material tribocharging in grains can result in important long-range electrostatic interactions. However, how these electrostatic interactions contribute to particle clustering remains elusive, primarily due to the lack of direct, detailed observations. Using a high-speed camera that falls with a stream charged grains, we observe for the first time how charged grains can undergo attractive as well as repulsive Kepler-like orbits. Charged particles can be captured in their mutual electrostatic potential and form clusters via multiple bounces. Dielectric polarization effects are directly observed, which lead to additional attractive forces and stabilize "molecule-like" arrangements of charged particles. Third, we have developed a new method to study the charge transfer of microscopic particles based on acoustic levitation techniques. This method allows us to narrow the complex problem of many-particle charging down to precise charge measurements of a single sub-millimeter particle colliding with a target plate. By simply attaching nonpolar groups onto glass surfaces, we show that the contact charging of a particle is highly dependent on hydrophobicity. Charging between a hydrophilic and a hydrophobic surface is enhanced in a basic atmosphere and suppressed in an acidic one. Moreover, hydrophobicity is also found to play a key role in particle charging driven by an external electric field. These results strongly support the idea that aqueous-ion transfer is responsible for the particle contact charging phenomenon.

Self-consistent treatment of electrostatics in molecular DNA braiding through external forces.

PubMed

Lee, Dominic J

2014-06-01

In this paper we consider a physical system in which two DNA molecules braid about each other. The distance between the two molecular ends, on either side of the braid, is held at a distance much larger than supercoiling radius of the braid. The system is subjected to an external pulling force, and a moment that induces the braiding. In a model, developed for understanding such a system, we assume that each molecule can be divided into a braided and unbraided section. We also suppose that the DNA is nicked so that there is no constraint of the individual linking numbers of the molecules. Included in the model are steric and electrostatic interactions, thermal fluctuations of the braided and unbraided sections of the molecule, as well as the constraint on the braid linking (catenation) number. We compare two approximations used in estimating the free energy of the braided section. One is where the amplitude of undulations of one molecule with respect to the other is determined only by steric interactions. The other is a self-consistent determination of the mean-squared amplitude of these undulations. In this second approximation electrostatics should play an important role in determining this quantity, as suggested by physical arguments. We see that if the electrostatic interaction is sufficiently large there are indeed notable differences between the two approximations. We go on to test the self-consistent approximation-included in the full model-against experimental data for such a system, and we find good agreement. However, there seems to be a slight left-right-handed braid asymmetry in some of the experimental results. We discuss what might be the origin of this small asymmetry.

Hydrogen bonding and pi-stacking: how reliable are force fields? A critical evaluation of force field descriptions of nonbonded interactions.

PubMed

Paton, Robert S; Goodman, Jonathan M

2009-04-01

We have evaluated the performance of a set of widely used force fields by calculating the geometries and stabilization energies for a large collection of intermolecular complexes. These complexes are representative of a range of chemical and biological systems for which hydrogen bonding, electrostatic, and van der Waals interactions play important roles. Benchmark energies are taken from the high-level ab initio values in the JSCH-2005 and S22 data sets. All of the force fields underestimate stabilization resulting from hydrogen bonding, but the energetics of electrostatic and van der Waals interactions are described more accurately. OPLSAA gave a mean unsigned error of 2 kcal mol(-1) for all 165 complexes studied, and outperforms DFT calculations employing very large basis sets for the S22 complexes. The magnitude of hydrogen bonding interactions are severely underestimated by all of the force fields tested, which contributes significantly to the overall mean error; if complexes which are predominantly bound by hydrogen bonding interactions are discounted, the mean unsigned error of OPLSAA is reduced to 1 kcal mol(-1). For added clarity, web-based interactive displays of the results have been developed which allow comparisons of force field and ab initio geometries to be performed and the structures viewed and rotated in three dimensions.

Protein adsorption onto CF(3)-terminated oligo(ethylene glycol) containing self-assembled monolayers (SAMs): the influence of ionic strength and electrostatic forces.

PubMed

Bonnet, Nelly; O'Hagan, David; Hähner, Georg

2010-05-07

Oligo(ethylene glycol) (OEG) containing self-assembled monolayers (SAMs) on gold are known for their protein resistant properties. The underlying molecular mechanisms and the contributions of the interactions involved, however, are still not completely understood. It is known that electrostatic, van der Waals, hydrophobic, and hydration forces all play a role in the interaction between proteins and surfaces, but it is difficult to study their influence separately and to quantify their contributions. In the present study we investigate five different OEG containing SAMs and the influence of the ionic strength and the electrostatic component on the amount of a negatively charged protein (fibrinogen) that adsorbs onto them. Atomic force microscopy (AFM) was employed to record force-distance curves with hydrophobic probes depending on the ion concentration, and the amount of the protein that adsorbs relative to a hydrophobic surface was quantified using ellipsometry. The findings suggest that electrostatic forces can create a very low energy barrier thus only slightly decreasing the number of negatively charged proteins in solution with sufficient energy to approach the surface closely, and have a rather small influence on the amount that adsorbs. The films we investigated were not protein resistant. This supports other studies, reporting that a strong short-range repulsion as for example caused by hydration forces is required to make these films resistant to the non-specific adsorption of proteins.

Adsorption of different amphiphilic molecules onto polystyrene latices.

PubMed

Jódar-Reyes, A B; Ortega-Vinuesa, J L; Martín-Rodríguez, A

2005-02-15

In order to know the influence of the surface characteristics and the chain properties on the adsorption of amphiphilic molecules onto polystyrene latex, a set of experiments to study the adsorption of ionic surfactants, nonionic surfactants and an amphiphilic synthetic peptide on different latex dispersions was performed. The adsorbed amount versus the equilibrium surfactant concentration was determined. The main adsorption mechanism was the hydrophobic attraction between the nonpolar tail of the molecule and the hydrophobic regions of the latex surface. This attraction overcame the electrostatic repulsion between chains and latex surface with identical charge sign. However, the electrostatic interactions chain-surface and chain-chain also played a role. General patterns for the adsorption of ionic chains on charged latex surfaces could be established. Regarding the shape, the isotherms presented different plateaus corresponding to electrostatic effects and conformational changes. The surfactant size also affects the adsorption results: the higher the hydrophilic moiety in the surfactant molecule the lower the adsorbed amount.

Structural and motional contributions of the Bacillus subtilis ClpC N-domain in adaptor protein interactions

PubMed Central

Kojetin, Douglas J.; McLaughlin, Patrick D.; Thompson, Richele J.; Dubnau, David; Prepiak, Peter; Rance, Mark; Cavanagh, John

2009-01-01

Summary The AAA+ superfamily protein ClpC is a key regulator of cell development in Bacillus subtilis. As part of a large oligomeric complex, ClpC controls an array of cellular processes by recognizing, unfolding, and providing misfolded and aggregated proteins as substrates for the ClpP peptidase. ClpC is unique compared to other HSP100/Clp proteins, as it requires an adaptor protein for all fundamental activities. The NMR solution structure of the N-terminal repeat domain of ClpC (N-ClpCR) comprises two structural repeats of a four-helix motif. NMR experiments used to map the MecA adaptor protein interaction surface of N-ClpCR reveal that regions involved in the interaction possess conformational flexibility, as well as conformational exchange on the μs-ms time-scale. The electrostatic surface of N-ClpCR differs substantially compared to the N-domain of Escherichia coli ClpA and ClpB, suggesting that the electrostatic surface characteristics of HSP100/Clp N-domains may play a role in adaptor protein and substrate interaction specificity, and perhaps contribute to the unique adaptor protein requirement of ClpC. PMID:19361434

DNA-DNA interaction beyond the ground state

NASA Astrophysics Data System (ADS)

Lee, D. J.; Wynveen, A.; Kornyshev, A. A.

2004-11-01

The electrostatic interaction potential between DNA duplexes in solution is a basis for the statistical mechanics of columnar DNA assemblies. It may also play an important role in recombination of homologous genes. We develop a theory of this interaction that includes thermal torsional fluctuations of DNA using field-theoretical methods and Monte Carlo simulations. The theory extends and rationalizes the earlier suggested variational approach which was developed in the context of a ground state theory of interaction of nonhomologous duplexes. It shows that the heuristic variational theory is equivalent to the Hartree self-consistent field approximation. By comparison of the Hartree approximation with an exact solution based on the QM analogy of path integrals, as well as Monte Carlo simulations, we show that this easily analytically-tractable approximation works very well in most cases. Thermal fluctuations do not remove the ability of DNA molecules to attract each other at favorable azimuthal conformations, neither do they wash out the possibility of electrostatic “snap-shot” recognition of homologous sequences, considered earlier on the basis of ground state calculations. At short distances DNA molecules undergo a “torsional alignment transition,” which is first order for nonhomologous DNA and weaker order for homologous sequences.

Molecular simulation study of feruloyl esterase adsorption on charged surfaces: effects of surface charge density and ionic strength.

PubMed

Liu, Jie; Peng, Chunwang; Yu, Gaobo; Zhou, Jian

2015-10-06

The surrounding conditions, such as surface charge density and ionic strength, play an important role in enzyme adsorption. The adsorption of a nonmodular type-A feruloyl esterase from Aspergillus niger (AnFaeA) on charged surfaces was investigated by parallel tempering Monte Carlo (PTMC) and all-atom molecular dynamics (AAMD) simulations at different surface charge densities (±0.05 and ±0.16 C·m(-2)) and ionic strengths (0.007 and 0.154 M). The adsorption energy, orientation, and conformational changes were analyzed. Simulation results show that whether AnFaeA can adsorb onto a charged surface is mainly controlled by electrostatic interactions between AnFaeA and the charged surface. The electrostatic interactions between AnFaeA and charged surfaces are weakened when the ionic strength increases. The positively charged surface at low surface charge density and high ionic strength conditions can maximize the utilization of the immobilized AnFaeA. The counterion layer plays a key role in the adsorption of AnFaeA on the negatively charged COOH-SAM. The native conformation of AnFaeA is well preserved under all of these conditions. The results of this work can be used for the controlled immobilization of AnFaeA.

Bounding the electrostatic free energies associated with linear continuum models of molecular solvation.

PubMed

Bardhan, Jaydeep P; Knepley, Matthew G; Anitescu, Mihai

2009-03-14

The importance of electrostatic interactions in molecular biology has driven extensive research toward the development of accurate and efficient theoretical and computational models. Linear continuum electrostatic theory has been surprisingly successful, but the computational costs associated with solving the associated partial differential equations (PDEs) preclude the theory's use in most dynamical simulations. Modern generalized-Born models for electrostatics can reproduce PDE-based calculations to within a few percent and are extremely computationally efficient but do not always faithfully reproduce interactions between chemical groups. Recent work has shown that a boundary-integral-equation formulation of the PDE problem leads naturally to a new approach called boundary-integral-based electrostatics estimation (BIBEE) to approximate electrostatic interactions. In the present paper, we prove that the BIBEE method can be used to rigorously bound the actual continuum-theory electrostatic free energy. The bounds are validated using a set of more than 600 proteins. Detailed numerical results are presented for structures of the peptide met-enkephalin taken from a molecular-dynamics simulation. These bounds, in combination with our demonstration that the BIBEE methods accurately reproduce pairwise interactions, suggest a new approach toward building a highly accurate yet computationally tractable electrostatic model.

Bounding the electrostatic free energies associated with linear continuum models of molecular solvation

NASA Astrophysics Data System (ADS)

Bardhan, Jaydeep P.; Knepley, Matthew G.; Anitescu, Mihai

2009-03-01

The importance of electrostatic interactions in molecular biology has driven extensive research toward the development of accurate and efficient theoretical and computational models. Linear continuum electrostatic theory has been surprisingly successful, but the computational costs associated with solving the associated partial differential equations (PDEs) preclude the theory's use in most dynamical simulations. Modern generalized-Born models for electrostatics can reproduce PDE-based calculations to within a few percent and are extremely computationally efficient but do not always faithfully reproduce interactions between chemical groups. Recent work has shown that a boundary-integral-equation formulation of the PDE problem leads naturally to a new approach called boundary-integral-based electrostatics estimation (BIBEE) to approximate electrostatic interactions. In the present paper, we prove that the BIBEE method can be used to rigorously bound the actual continuum-theory electrostatic free energy. The bounds are validated using a set of more than 600 proteins. Detailed numerical results are presented for structures of the peptide met-enkephalin taken from a molecular-dynamics simulation. These bounds, in combination with our demonstration that the BIBEE methods accurately reproduce pairwise interactions, suggest a new approach toward building a highly accurate yet computationally tractable electrostatic model.

[Noncovalent cation-π interactions--their role in nature].

PubMed

Fink, Krzysztof; Boratyński, Janusz

2014-11-07

Non-covalent interactions play an extremely important role in organisms. The main non-covalent interactions in nature are: ion-ion interactions, dipole-dipole interactions, hydrogen bonds, and van der Waals interactions. A new kind of intermolecular interactions--cation-π interactions--is gaining increasing attention. These interactions occur between a cation and a π system. The main contributors to cation-π interactions are electrostatic, polarization and, to a lesser extent, dispersion interactions. At first, cation-π interactions were studied in a gas phase, with metal cation-aromatic system complexes. The characteristics of these complexes are as follows: an increase of cation atomic number leads to a decrease of interaction energy, and an increase of cation charge leads to an increase of interaction energy. Aromatic amino acids bind with metal cations mainly through interactions with their main chain. Nevertheless, cation-π interaction with a hydrophobic side chain significantly enhances binding energy. In water solutions most cations preferentially interact with water molecules rather than aromatic systems. Cation-π interactions occur in environments with lower accessibility to a polar solvent. Cation-π interactions can have a stabilizing role on the secondary, tertiary and quaternary structure of proteins. These interactions play an important role in substrate or ligand binding sites in many proteins, which should be taken into consideration when the screening of effective inhibitors for these proteins is carried out. Cation-π interactions are abundant and play an important role in many biological processes.

Effect of electrostatic interaction between fluoxetine and lipid membranes on the partitioning of fluoxetine investigated using second derivative spectrophotometry and FTIR.

PubMed

Do, Tien T T; Dao, Uyen P N; Bui, Huong T; Nguyen, Trang T

2017-10-01

The interaction between a drug molecule and lipid bilayers is highly important regarding the pharmaceutical activity of the drug. In this study, the interaction of fluoxetine, a well-known selective serotonin reuptake inhibitor antidepressant and lipid bilayers composed of 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was studied from the aspect of electrostatics using second derivative spectrophotometry and Fourier transform infrared spectroscopy (FTIR) in order to provide insights into the drug behavior. Changing pH from 7.4 to 9.5 to increases the neutral state of fluoxetine, the partitioning of fluoxetine into the zwitterionic DPPC large unilamellar vesicles (LUVs) was increased whereas it was reduced into the negatively charged DPPG LUVs. Fluoxetine was found to exhibit a disordering effect on the acyl chains of DPPC and DPPG bilayers upon its partitioning. In addition, increasing concentration of NaCl lessened the binding of fluoxetine into DPPG bilayers due to the reduction in electrostatic attraction between positively charged fluoxetine and negatively charged DPPG LUVs. In addition, the FTIR study revealed that increasing the NaCl concentration could trigger the shift to higher frequency of the CH 2 stretching as well as the notable blue shift in the PO 2 - regions of DPPG, indicating that fluoxetine had deeper penetration into DPPG LUVs. The differences in the NaCl concentration showed a negligible effect on the incorporation of fluoxetine into the zwitterionic DPPC LUVs. In summary, the electrostatic interaction plays an important role on the partitioning of a cationic amphiphilic SSIR drug into the lipid bilayers and the drug partitioning induces the lipids' conformational change. These imply a possible influence on the drug pharmacology. Copyright © 2017 Elsevier B.V. All rights reserved.

Brownian dynamics simulations of polyelectrolyte adsorption in shear flow with hydrodynamic interaction

NASA Astrophysics Data System (ADS)

Hoda, Nazish; Kumar, Satish

2007-12-01

The adsorption of single polyelectrolyte molecules in shear flow is studied using Brownian dynamics simulations with hydrodynamic interaction (HI). Simulations are performed with bead-rod and bead-spring chains, and electrostatic interactions are incorporated through a screened Coulombic potential with excluded volume accounted for by the repulsive part of a Lennard-Jones potential. A correction to the Rotne-Prager-Yamakawa tensor is derived that accounts for the presence of a planar wall. The simulations show that migration away from an uncharged wall, which is due to bead-wall HI, is enhanced by increases in the strength of flow and intrachain electrostatic repulsion, consistent with kinetic theory predictions. When the wall and polyelectrolyte are oppositely charged, chain behavior depends on the strength of electrostatic screening. For strong screening, chains get depleted from a region close to the wall and the thickness of this depletion layer scales as N1/3Wi2/3 at high Wi, where N is the chain length and Wi is the Weissenberg number. At intermediate screening, bead-wall electrostatic attraction competes with bead-wall HI, and it is found that there is a critical Weissenberg number for desorption which scales as N-1/2κ-3(lB∣σq∣)3/2, where κ is the inverse screening length, lB is the Bjerrum length, σ is the surface charge density, and q is the bead charge. When the screening is weak, adsorbed chains are observed to align in the vorticity direction at low shear rates due to the effects of repulsive intramolecular interactions. At higher shear rates, the chains align in the flow direction. The simulation method and results of this work are expected to be useful for a number of applications in biophysics and materials science in which polyelectrolyte adsorption plays a key role.

Identification of a conserved 8 aa insert in the PIP5K protein in the Saccharomycetaceae family of fungi and the molecular dynamics simulations and structural analysis to investigate its potential functional role.

PubMed

Khadka, Bijendra; Gupta, Radhey S

2017-08-01

Homologs of the phosphatidylinositol-4-phosphate-5-kinase (PIP5K), which controls a multitude of essential cellular functions, contain a 8 aa insert in a conserved region that is specific for the Saccharomycetaceae family of fungi. Using structures of human PIP4K proteins as templates, structural models were generated of the Saccharomyces cerevisiae and human PIP5K proteins. In the modeled S. cerevisiae PIP5K, the 8 aa insert forms a surface exposed loop, present on the same face of the protein as the activation loop of the kinase domain. Electrostatic potential analysis indicates that the residues from 8 aa conserved loop form a highly positively charged surface patch, which through electrostatic interaction with the anionic portions of phospholipid head groups, is expected to play a role in the membrane interaction of the yeast PIP5K. To unravel this prediction, molecular dynamics (MD) simulations were carried out to examine the binding interaction of PIP5K, either containing or lacking the conserved signature insert, with two different membrane lipid bilayers. The results from MD studies provide insights concerning the mechanistic of interaction of PIP5K with lipid bilayer, and support the contention that the identified 8 aa conserved insert in fungal PIP5K plays an important role in the binding of this protein with membrane surface. Proteins 2017; 85:1454-1467. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The cation-π interaction.

PubMed

Dougherty, Dennis A

2013-04-16

The chemistry community now recognizes the cation-π interaction as a major force for molecular recognition, joining the hydrophobic effect, the hydrogen bond, and the ion pair in determining macromolecular structure and drug-receptor interactions. This Account provides the author's perspective on the intellectual origins and fundamental nature of the cation-π interaction. Early studies on cyclophanes established that water-soluble, cationic molecules would forego aqueous solvation to enter a hydrophobic cavity if that cavity was lined with π systems. Important gas phase studies established the fundamental nature of the cation-π interaction. The strength of the cation-π interaction (Li(+) binds to benzene with 38 kcal/mol of binding energy; NH4(+) with 19 kcal/mol) distinguishes it from the weaker polar-π interactions observed in the benzene dimer or water-benzene complexes. In addition to the substantial intrinsic strength of the cation-π interaction in gas phase studies, the cation-π interaction remains energetically significant in aqueous media and under biological conditions. Many studies have shown that cation-π interactions can enhance binding energies by 2-5 kcal/mol, making them competitive with hydrogen bonds and ion pairs in drug-receptor and protein-protein interactions. As with other noncovalent interactions involving aromatic systems, the cation-π interaction includes a substantial electrostatic component. The six (four) C(δ-)-H(δ+) bond dipoles of a molecule like benzene (ethylene) combine to produce a region of negative electrostatic potential on the face of the π system. Simple electrostatics facilitate a natural attraction of cations to the surface. The trend for (gas phase) binding energies is Li(+) > Na(+) > K(+) > Rb(+): as the ion gets larger the charge is dispersed over a larger sphere and binding interactions weaken, a classical electrostatic effect. On other hand, polarizability does not define these interactions. Cyclohexane is more polarizable than benzene but a decidedly poorer cation binder. Many studies have documented cation-π interactions in protein structures, where lysine or arginine side chains interact with phenylalanine, tyrosine, or tryptophan. In addition, countless studies have established the importance of the cation-π interaction in a range of biological processes. Our work has focused on molecular neurobiology, and we have shown that neurotransmitters generally use a cation-π interaction to bind to their receptors. We have also shown that many drug-receptor interactions involve cation-π interactions. A cation-π interaction plays a critical role in the binding of nicotine to ACh receptors in the brain, an especially significant case. Other researchers have established important cation-π interactions in the recognition of the "histone code," in terpene biosynthesis, in chemical catalysis, and in many other systems.

The Cation-π Interaction

PubMed Central

DOUGHERTY, DENNIS A.

2014-01-01

CONSPECTUS The chemistry community now recognizes the cation-π interaction as a major force for molecular recognition, joining the hydrophobic effect, the hydrogen bond, and the ion pair in determining macromolecular structure and drug-receptor interactions. This Account provides the author’s perspective on the intellectual origins and fundamental nature of the cation-π interaction. Early studies on cyclophanes established that water-soluble, cationic molecules would forgo aqueous solvation to enter a hydrophobic cavity if that cavity was lined with π systems. Important gas phase studies established the fundamental nature of the cation-π interaction. The strength of the cation-π interaction – Li+ binds to benzene with 38 kcal/mol of binding energy; NH4+ with 19 kcal/mol– distinguishes it from the weaker polar-π interactions observed in the benzene dimer or water-benzene complexes. In addition to the substantial intrinsic strength of the cation-π interaction in gas phase studies, the cation-π interaction remains energetically significant in aqueous media and under biological conditions. Many studies have shown that cation-π interactions can enhance binding energies by 2 – 5 kcal/mol, making them competitive with hydrogen bonds and ion pairs in drug-receptor and protein-protein interactions. As with other noncovalent interactions involving aromatic systems, the cation-π interaction includes a substantial electrostatic component. The six (four) Cδ−–Hδ+ bond dipoles of a molecule like benzene (ethylene) combine to produce a region of negative electrostatic potential on the face of the π system. Simple electrostatics facilitate a natural attraction of cations to the surface. The trend for (gas phase) binding energies is Li+>Na+>K+>Rb+: as the ion gets larger the charge is dispersed over a larger sphere and binding interactions weaken, a classical electrostatic effect. On other hand, polarizability does not define these interactions. Cyclohexane is more polarizable than benzene, but a decidedly poorer cation binder. Many studies have documented cation-π interactions in protein structures, where Lys or Arg side chains interact with Phe, Tyr, or Trp. In addition, countless studies have established the importance of cation-π interaction in a range of biological processes. Our work has focused on molecular neurobiology, and we have shown that neurotransmitters generally use a cation-π interaction to bind to their receptors. We have also shown that many drug-receptor interactions involve cation-π interactions. A cation-π interaction plays a critical role in the binding of nicotine to ACh receptors in the brain, an especially significant case. Other researchers have established important cation-π interactions in the recognition of the “histone code,” in terpene biosynthesis, in chemical catalysis, and in many other systems. PMID:23214924

Limiting assumptions in molecular modeling: electrostatics.

PubMed

Marshall, Garland R

2013-02-01

Molecular mechanics attempts to represent intermolecular interactions in terms of classical physics. Initial efforts assumed a point charge located at the atom center and coulombic interactions. It is been recognized over multiple decades that simply representing electrostatics with a charge on each atom failed to reproduce the electrostatic potential surrounding a molecule as estimated by quantum mechanics. Molecular orbitals are not spherically symmetrical, an implicit assumption of monopole electrostatics. This perspective reviews recent evidence that requires use of multipole electrostatics and polarizability in molecular modeling.

Intrinsically disordered inhibitor of glutamine synthetase is a functional protein with random-coil-like pKa values.

PubMed

Cozza, Concetta; Neira, José L; Florencio, Francisco J; Muro-Pastor, M Isabel; Rizzuti, Bruno

2017-06-01

The sequential action of glutamine synthetase (GS) and glutamate synthase (GOGAT) in cyanobacteria allows the incorporation of ammonium into carbon skeletons. In the cyanobacterium Synechocystis sp. PCC 6803, the activity of GS is modulated by the interaction with proteins, which include a 65-residue-long intrinsically disordered protein (IDP), the inactivating factor IF7. This interaction is regulated by the presence of charged residues in both IF7 and GS. To understand how charged amino acids can affect the binding of an IDP with its target and to provide clues on electrostatic interactions in disordered states of proteins, we measured the pK a values of all IF7 acidic groups (Glu32, Glu36, Glu38, Asp40, Asp58, and Ser65, the backbone C-terminus) at 100 mM NaCl concentration, by using NMR spectroscopy. We also obtained solution structures of IF7 through molecular dynamics simulation, validated them on the basis of previous experiments, and used them to obtain theoretical estimates of the pK a values. Titration values for the two Asp and three Glu residues of IF7 were similar to those reported for random-coil models, suggesting the lack of electrostatic interactions around these residues. Furthermore, our results suggest the presence of helical structure at the N-terminus of the protein and of conformational changes at acidic pH values. The overall experimental and in silico findings suggest that local interactions and conformational equilibria do not play a role in determining the electrostatic features of the acidic residues of IF7. © 2017 The Protein Society.

Electrostatic lipid-protein interactions sequester the curli amyloid fold on the lipopolysaccharide membrane surface.

PubMed

Swasthi, Hema M; Mukhopadhyay, Samrat

2017-12-01

Curli is a functional amyloid protein in the extracellular matrix of enteric Gram-negative bacteria. Curli is assembled at the cell surface and consists of CsgA, the major subunit of curli, and a membrane-associated nucleator protein, CsgB. Oligomeric intermediates that accumulate during the lag phase of amyloidogenesis are generally toxic, but the underlying mechanism by which bacterial cells overcome this toxicity during curli assembly at the surface remains elusive. Here, we elucidated the mechanism of curli amyloidogenesis and provide molecular insights into the strategy by which bacteria can potentially bypass the detrimental consequences of toxic amyloid intermediates. Using a diverse range of biochemical and biophysical tools involving circular dichroism, fluorescence, Raman spectroscopy, and atomic force microscopy imaging, we characterized the molecular basis of the interaction of CsgB with a membrane-mimetic anionic surfactant as well as with lipopolysaccharide (LPS) constituting the outer leaflet of Gram-negative bacteria. Aggregation studies revealed that the electrostatic interaction of the positively charged C-terminal region of the protein with a negatively charged head group of surfactant/LPS promotes a protein-protein interaction that results in facile amyloid formation without a detectable lag phase. We also show that CsgB, in the presence of surfactant/LPS, accelerates the fibrillation rate of CsgA by circumventing the lag phase during nucleation. Our findings suggest that the electrostatic interactions between lipid and protein molecules play a pivotal role in efficiently sequestering the amyloid fold of curli on the membrane surface without significant accumulation of toxic oligomeric intermediates. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Molecular mechanics and dynamics studies on the interaction of gallic acid with collagen-like peptides

NASA Astrophysics Data System (ADS)

Madhan, B.; Thanikaivelan, P.; Subramanian, V.; Raghava Rao, J.; Unni Nair, Balachandran; Ramasami, T.

2001-10-01

Molecular modelling approaches have been used to understand the interaction of collagen-like peptides with gallic acid, which mimic vegetable tanning processes involved in protein stabilization. Several interaction sites have been identified and the binding energies of the complexes have been calculated. The calculated binding energies for various geometries are in the range 6-13 kcal/mol. It is found that some complexes exhibit hydrogen bonding, and electrostatic interaction plays a dominant role in the stabilization of the peptide by gallic acid. The π-OH type of interaction is also observed in the peptide stabilization. Molecular dynamics (MD) simulation for 600 ps revealed the possibility of hydrogen bonding between the collagen-like peptide and gallic acid.

Structural analysis of Arabidopsis thaliana nucleoside diphosphate kinase-2 for phytochrome-mediated light signaling.

PubMed

Im, Young Jun; Kim, Jeong-Il; Shen, Yu; Na, Young; Han, Yun-Jeong; Kim, Seong-Hee; Song, Pill-Soon; Eom, Soo Hyun

2004-10-22

In plants, nucleoside diphosphate kinases (NDPKs) play a key role in the signaling of both stress and light. However, little is known about the structural elements involved in their function. Of the three NDPKs (NDPK1-NDPK3) expressed in Arabidopsis thaliana, NDPK2 is involved in phytochrome-mediated signal transduction. In this study, we found that the binding of dNDP or NTP to NDPK2 strengthens the interaction significantly between activated phytochrome and NDPK2. To better understand the structural basis of the phytochrome-NDPK2 interaction, we determined the X-ray structures of NDPK1, NDPK2, and dGTP-bound NDPK2 from A.thaliana at 1.8A, 2.6A, and 2.4A, respectively. The structures showed that nucleotide binding caused a slight conformational change in NDPK2 that was confined to helices alphaA and alpha2. This suggests that the presence of nucleotide in the active site and/or the evoked conformational change contributes to the recognition of NDPK2 by activated phytochrome. In vitro binding assays showed that only NDPK2 interacted specifically with the phytochrome and the C-terminal regulatory domain of phytochrome is involved in the interaction. A domain swap experiment between NDPK1 and NDPK2 showed that the variable C-terminal region of NDPK2 is important for the activation by phytochrome. The structure of Arabidopsis NDPK1 and NDPK2 showed that the isoforms share common electrostatic surfaces at the nucleotide-binding site, but the variable C-terminal regions have distinct electrostatic charge distributions. These findings suggest that the binding of nucleotide to NDPK2 plays a regulatory role in phytochrome signaling and that the C-terminal extension of NDPK2 provides a potential binding surface for the specific interaction with phytochromes.

Role of electrostatic interactions in the assembly of empty spherical viral capsids

NASA Astrophysics Data System (ADS)

Šiber, Antonio; Podgornik, Rudolf

2007-12-01

We examine the role of electrostatic interactions in the assembly of empty spherical viral capsids. The charges on the protein subunits that make the viral capsid mutually interact and are expected to yield electrostatic repulsion acting against the assembly of capsids. Thus, attractive protein-protein interactions of nonelectrostatic origin must act to enable the capsid formation. We investigate whether the interplay of repulsive electrostatic and attractive interactions between the protein subunits can result in the formation of spherical viral capsids of a preferred radius. For this to be the case, we find that the attractive interactions must depend on the angle between the neighboring protein subunits (i.e., on the mean curvature of the viral capsid) so that a particular angle(s) is (are) preferred energywise. Our results for the electrostatic contributions to energetics of viral capsids nicely correlate with recent experimental determinations of the energetics of protein-protein contacts in the hepatitis B virus [P. Ceres A. Zlotnick, Biochemistry 41, 11525 (2002)].

Coupled electrostatic and material surface stresses yield anomalous particle interactions and deformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kemp, B. A., E-mail: bkemp@astate.edu; Nikolayev, I.; Sheppard, C. J.

2016-04-14

Like-charges repel, and opposite charges attract. This fundamental tenet is a result of Coulomb's law. However, the electrostatic interactions between dielectric particles remain topical due to observations of like-charged particle attraction and the self-assembly of colloidal systems. Here, we show, using both an approximate description and an exact solution of Maxwell's equations, that nonlinear charged particle forces result even for linear material systems and can be responsible for anomalous electrostatic interactions such as like-charged particle attraction and oppositely charged particle repulsion. Furthermore, these electrostatic interactions and the deformation of such particles have fundamental implications for our understanding of macroscopic electrodynamics.

Solar Wind Strahl Broadening by Self-Generated Plasma Waves

NASA Technical Reports Server (NTRS)

Pavan, J.; Vinas, A. F.; Yoon, P. H.; Ziebell, L. F.; Gaelzer, R.

2013-01-01

This Letter reports on the results of numerical simulations which may provide a possible explanation for the strahl broadening during quiet solar conditions. The relevant processes involved in the broadening are due to kinetic quasi-linear wave-particle interaction. Making use of static analytical electron distribution in an inhomogeneous field, it is found that self-generated electrostatic waves at the plasma frequency, i.e., Langmuir waves, are capable of scattering the strahl component, resulting in energy and pitch-angle diffusion that broadens its velocity distribution significantly. The present theoretical results provide an alternative or complementary explanation to the usual whistler diffusion scenario, suggesting that self-induced electrostatic waves at the plasma frequency might play a key role in broadening the solar wind strahl during quiet solar conditions.

Electro-osmosis over inhomogeneously charged surfaces in presence of non-electrostatic ion-ion interactions

NASA Astrophysics Data System (ADS)

Ghosh, Uddipta; Chakraborty, Suman

2016-06-01

In this study, we attempt to bring out a generalized formulation for electro-osmotic flows over inhomogeneously charged surfaces in presence of non-electrostatic ion-ion interactions. To this end, we start with modified electro-chemical potential of the individual species and subsequently use it to derive modified Nernst-Planck equation accounting for the ionic fluxes generated because of the presence of non-electrostatic potential. We establish what we refer to as the Poisson-Helmholtz-Nernst-Planck equations, coupled with the Navier-Stokes equations, to describe the complete transport process. Our analysis shows that the presence of non-electrostatic interactions between the ions results in an excess body force on the fluid, and modifies the osmotic pressure as well, which has hitherto remained unexplored. We further apply our analysis to a simple geometry, in an effort to work out the Smoluchowski slip velocity for thin electrical double layer limits. To this end, we employ singular perturbation and develop a general framework for the asymptotic analysis. Our calculations reveal that the final expression for slip velocity remains the same as that without accounting for non-electrostatic interactions. However, the presence of non-electrostatic interactions along with ion specificity can significantly change the quantitative behavior of Smoluchowski slip velocity. We subsequently demonstrate that the presence of non-electrostatic interactions may significantly alter the effective interfacial potential, also termed as the "Zeta potential." Our analysis can potentially act as a guide towards the prediction and possibly quantitative determination of the implications associated with the existence of non-electrostatic potential, in an electrokinetic transport process.

DEVELOPMENT OF A MODEL THAT CONTAINS BOTH MULTIPOLE MOMENTS AND GAUSSIANS FOR THE CALCULATION OF MOLECULAR ELECTROSTATIC POTENTIALS

EPA Science Inventory

The electrostatic interaction is a critical component of intermolecular interactions in biological processes. Rapid methods for the computation and characterization of the molecular electrostatic potential (MEP) that segment the molecular charge distribution and replace this cont...

Collisionless coupling processes in AMPTE releases

NASA Technical Reports Server (NTRS)

Lui, A. T. Y.

1990-01-01

An evaluation is made of results obtained to date by in situ measurements, numerical simulations, and theoretical considerations of Active Magnetospheric Particle Tracer Explorer chemical releases bearing on the nature of collisionless coupling processes. It is noted that both laminar and turbulent forces act to couple the solar wind momentum and energy to the release cloud; the magnetic field compression formed in this interaction plays an important intermediary role in coupling the two plasmas, and the intense electrostatic turbulence generated enhances the interaction. A scenario accounting for several features in the observed evolution of the December 27, 1984 artificial comet release is presented.

Attractive Interactions between Heteroallenes and the Cucurbituril Portal.

PubMed

Reany, Ofer; Li, Amanda; Yefet, Maayan; Gilson, Michael K; Keinan, Ehud

2017-06-21

In this paper, we report on the noteworthy attractive interaction between organic azides and the portal carbonyls of cucurbiturils. Five homologous bis-α,ω-azidoethylammonium alkanes were prepared, where the number of methylene groups between the ammonium groups ranges from 4 to 8. Their interactions with cucurbit[6]uril were studied by NMR spectroscopy, IR spectroscopy, X-ray crystallography, and computational methods. Remarkably, while the distance between the portal plane and most atoms at the guest end groups increases progressively with the molecular size, the β-nitrogen atoms maintain a constant distance from the portal plane in all homologues, pointing at a strong attractive interaction between the azide group and the portal. Both crystallography and NMR support a specific electrostatic interaction between the carbonyl and the azide β-nitrogen, which stabilizes the canonical resonance form with positive charge on the β-nitrogen and negative charge on the γ-nitrogen. Quantum computational analyses strongly support electrostatics, in the form of orthogonal dipole-dipole interaction, as the main driver for this attraction. The alternative mechanism of n → π* orbital delocalization does not seem to play a significant role in this interaction. The computational studies also indicate that the interaction is not limited to azides, but generalizes to other isoelectronic heteroallene functions, such as isocyanate and isothiocyanate. This essentially unexploited attractive interaction could be more broadly utilized as a tool not only in relation to cucurbituril chemistry, but also for the design of novel supramolecular architectures.

High-resolution neutron and X-ray diffraction room-temperature studies of an H-FABP-oleic acid complex: study of the internal water cluster and ligand binding by a transferred multipolar electron-density distribution.

PubMed

Howard, E I; Guillot, B; Blakeley, M P; Haertlein, M; Moulin, M; Mitschler, A; Cousido-Siah, A; Fadel, F; Valsecchi, W M; Tomizaki, Takashi; Petrova, T; Claudot, J; Podjarny, A

2016-03-01

Crystal diffraction data of heart fatty acid binding protein (H-FABP) in complex with oleic acid were measured at room temperature with high-resolution X-ray and neutron protein crystallography (0.98 and 1.90 Å resolution, respectively). These data provided very detailed information about the cluster of water molecules and the bound oleic acid in the H-FABP large internal cavity. The jointly refined X-ray/neutron structure of H-FABP was complemented by a transferred multipolar electron-density distribution using the parameters of the ELMAMII library. The resulting electron density allowed a precise determination of the electrostatic potential in the fatty acid (FA) binding pocket. Bader's quantum theory of atoms in molecules was then used to study interactions involving the internal water molecules, the FA and the protein. This approach showed H⋯H contacts of the FA with highly conserved hydrophobic residues known to play a role in the stabilization of long-chain FAs in the binding cavity. The determination of water hydrogen (deuterium) positions allowed the analysis of the orientation and electrostatic properties of the water molecules in the very ordered cluster. As a result, a significant alignment of the permanent dipoles of the water molecules with the protein electrostatic field was observed. This can be related to the dielectric properties of hydration layers around proteins, where the shielding of electrostatic interactions depends directly on the rotational degrees of freedom of the water molecules in the interface.

Electrostatics at the nanoscale.

PubMed

Walker, David A; Kowalczyk, Bartlomiej; de la Cruz, Monica Olvera; Grzybowski, Bartosz A

2011-04-01

Electrostatic forces are amongst the most versatile interactions to mediate the assembly of nanostructured materials. Depending on experimental conditions, these forces can be long- or short-ranged, can be either attractive or repulsive, and their directionality can be controlled by the shapes of the charged nano-objects. This Review is intended to serve as a primer for experimentalists curious about the fundamentals of nanoscale electrostatics and for theorists wishing to learn about recent experimental advances in the field. Accordingly, the first portion introduces the theoretical models of electrostatic double layers and derives electrostatic interaction potentials applicable to particles of different sizes and/or shapes and under different experimental conditions. This discussion is followed by the review of the key experimental systems in which electrostatic interactions are operative. Examples include electroactive and "switchable" nanoparticles, mixtures of charged nanoparticles, nanoparticle chains, sheets, coatings, crystals, and crystals-within-crystals. Applications of these and other structures in chemical sensing and amplification are also illustrated.

Study of interactions between hyaluronan and cationic surfactants by means of calorimetry, turbidimetry, potentiometry and conductometry.

PubMed

Krouská, J; Pekař, M; Klučáková, M; Šarac, B; Bešter-Rogač, M

2017-02-10

The thermodynamics of the micelle formation of the cationic surfactants tetradecyltrimethylammonium bromide (TTAB) and cetyltrimethylammonium bromide (CTAB) with and without the addition of hyaluronan of two molecular weights was studied in aqueous solution by titration calorimetry. Macroscopic phase separation, which was detected by calorimetry and also by conductometry, occurs when charges on the surfactant and hyaluronan are balanced. In contrast, turbidimetry and potentiometry showed hyaluronan-surfactant interactions at very low surfactant concentrations. The observed differences between systems prepared with CTAB and TTAB indicate that besides the electrostatic interactions, which probably predominate, hydrophobic effects also play a significant role in hyaluronan interactions with cationic surfactants. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Poisson-Helmholtz-Boltzmann model.

PubMed

Bohinc, K; Shrestha, A; May, S

2011-10-01

We present a mean-field model of a one-component electrolyte solution where the mobile ions interact not only via Coulomb interactions but also through a repulsive non-electrostatic Yukawa potential. Our choice of the Yukawa potential represents a simple model for solvent-mediated interactions between ions. We employ a local formulation of the mean-field free energy through the use of two auxiliary potentials, an electrostatic and a non-electrostatic potential. Functional minimization of the mean-field free energy leads to two coupled local differential equations, the Poisson-Boltzmann equation and the Helmholtz-Boltzmann equation. Their boundary conditions account for the sources of both the electrostatic and non-electrostatic interactions on the surface of all macroions that reside in the solution. We analyze a specific example, two like-charged planar surfaces with their mobile counterions forming the electrolyte solution. For this system we calculate the pressure between the two surfaces, and we analyze its dependence on the strength of the Yukawa potential and on the non-electrostatic interactions of the mobile ions with the planar macroion surfaces. In addition, we demonstrate that our mean-field model is consistent with the contact theorem, and we outline its generalization to arbitrary interaction potentials through the use of a Laplace transformation. © EDP Sciences / Società Italiana di Fisica / Springer-Verlag 2011

S/G-1: an ab initio force-field blending frozen Hermite Gaussian densities and distributed multipoles. Proof of concept and first applications to metal cations.

PubMed

Chaudret, Robin; Gresh, Nohad; Narth, Christophe; Lagardère, Louis; Darden, Thomas A; Cisneros, G Andrés; Piquemal, Jean-Philip

2014-09-04

We demonstrate as a proof of principle the capabilities of a novel hybrid MM'/MM polarizable force field to integrate short-range quantum effects in molecular mechanics (MM) through the use of Gaussian electrostatics. This lead to a further gain in accuracy in the representation of the first coordination shell of metal ions. It uses advanced electrostatics and couples two point dipole polarizable force fields, namely, the Gaussian electrostatic model (GEM), a model based on density fitting, which uses fitted electronic densities to evaluate nonbonded interactions, and SIBFA (sum of interactions between fragments ab initio computed), which resorts to distributed multipoles. To understand the benefits of the use of Gaussian electrostatics, we evaluate first the accuracy of GEM, which is a pure density-based Gaussian electrostatics model on a test Ca(II)-H2O complex. GEM is shown to further improve the agreement of MM polarization with ab initio reference results. Indeed, GEM introduces nonclassical effects by modeling the short-range quantum behavior of electric fields and therefore enables a straightforward (and selective) inclusion of the sole overlap-dependent exchange-polarization repulsive contribution by means of a Gaussian damping function acting on the GEM fields. The S/G-1 scheme is then introduced. Upon limiting the use of Gaussian electrostatics to metal centers only, it is shown to be able to capture the dominant quantum effects at play on the metal coordination sphere. S/G-1 is able to accurately reproduce ab initio total interaction energies within closed-shell metal complexes regarding each individual contribution including the separate contributions of induction, polarization, and charge-transfer. Applications of the method are provided for various systems including the HIV-1 NCp7-Zn(II) metalloprotein. S/G-1 is then extended to heavy metal complexes. Tested on Hg(II) water complexes, S/G-1 is shown to accurately model polarization up to quadrupolar response level. This opens up the possibility of embodying explicit scalar relativistic effects in molecular mechanics thanks to the direct transferability of ab initio pseudopotentials. Therefore, incorporating GEM-like electron density for a metal cation enable the introduction of nonambiguous short-range quantum effects within any point-dipole based polarizable force field without the need of an extensive parametrization.

Structural investigation of protein kinase C inhibitors

NASA Technical Reports Server (NTRS)

Barak, D.; Shibata, M.; Rein, R.

1991-01-01

The phospholipid and Ca2+ dependent protein kinase (PKC) plays an essential role in a variety of cellular events. Inhibition of PKC was shown to arrest growth in tumor cell cultures making it a target for possible antitumor therapy. Calphostins are potent inhibitors of PKC with high affinity for the enzyme regulatory site. Structural characteristics of calphostins, which confer the inhibitory activity, are investigated by comparing their optimized structures with the existing models for PKC activation. The resulting model of inhibitory activity assumes interaction with two out of the three electrostatic interaction sites postulated for activators. The model shows two sites of hydrophobic interaction and enables the inhibitory activity of gossypol to be accounted for.

Hydrolysis-controlled protein adsorption and antifouling behaviors of mixed charged self-assembled monolayer: A molecular simulation study.

PubMed

Liu, Jie; Zhou, Jian

2016-08-01

Understanding the mechanism of the antimicrobial and antifouling properties of mixed charged materials is of great significance. The interactions between human gamma fibrinogen (γFg) and mixed carboxylic methyl ether-terminated (COOCH3-) and trimethylamino-terminated (N(CH3)3(+)-) SAMs and the influence of hydrolysis were studied by molecular simulations. After hydrolysis, the mixed SAMs exhibit behaviors from antimicrobial to antifouling, since the COOCH3-thiols were translated into carboxylic acid (COO(-)-) terminated thiols, which carried a net charge of -1 e. Simulation results showed that the main differences between COOCH3-/N(CH3)3(+)-SAM and COO(-)-/N(CH3)3(+)-SAM are the charged property and the hydration layer above the surface. γFg could stably adsorb on the positively-charged COOCH3-/N(CH3)3(+)-SAM. The adsorption behavior is mainly induced by the strong electrostatic attraction. There is a single hydration layer bound to the surface, which is related to the N(CH3)3(+) groups. The van der Waals repulsion between γFg and the single hydration layer are not strong enough to compensate the strong electrostatic attraction. After hydrolysis, the positively-charged SAM was transferred to a neutral mixed charged surface, the electrostatic attraction between γFg and the surface disappears. Meanwhile, the SAM surface is covered by double hydration layers, which is induced by the N(CH3)3(+) and COO(-) groups; water molecules around COO(-) groups are obviously denser than that around N(CH3)3(+) groups. With the combined contribution from double hydration layers and the vanishment of electrostatic attraction, γFg is forced to desorb from the surface. After hydrolysis, the internal structure of mixed SAM appears more ordered due to the electrostatic interactions between charged groups on the top of SAMs. The antimicrobial and antifouling materials are of great importance in many biological applications. The strong hydration property of surfaces and the interactions between proteins and surfaces play a key role in resisting protein adsorption. The mixed SAMs, constructed from a 1:1 combination of COOCH3- and N(CH3)3(+)-terminated thiols, can induce protein adsorption mainly through the electrostatic interaction. When the COOCH3-terminated thiols were hydrolyzed to negatively charged COO(-)-terminated thiols, the mixed-charged SAMs switched from antimicrobial to antifouling. Due to the strong hydration property of the mixed charged SAMs, the adsorbed γFg moved away from the surface. Understanding the interactions between protein and mixed-charged SAMs in the atomistic level is important for the practical design and development of new antimicrobial and antifouling materials. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Ionizable Nitroxides for Studying Local Electrostatic Properties of Lipid Bilayers and Protein Systems by EPR.

PubMed

Voinov, Maxim A; Smirnov, Alex I

2015-01-01

Electrostatic interactions are known to play a major role in the myriad of biochemical and biophysical processes. Here, we describe biophysical methods to probe local electrostatic potentials of proteins and lipid bilayer systems that are based on an observation of reversible protonation of nitroxides by electron paramagnetic resonance (EPR). Two types of probes are described: (1) methanethiosulfonate derivatives of protonatable nitroxides for highly specific covalent modification of the cysteine's sulfhydryl groups and (2) spin-labeled phospholipids with a protonatable nitroxide tethered to the polar head group. The probes of both types report on their ionization state through changes in magnetic parameters and degree of rotational averaging, thus, allowing the electrostatic contribution to the interfacial pKa of the nitroxide, and, therefore, the local electrostatic potential to be determined. Due to their small molecular volume, these probes cause a minimal perturbation to the protein or lipid system. Covalent attachment secures the position of the reporter nitroxides. Experimental procedures to characterize and calibrate these probes by EPR, and also the methods to analyze the EPR spectra by simulations are outlined. The ionizable nitroxide labels and the nitroxide-labeled phospholipids described so far cover an exceptionally wide range of ca. 2.5-7.0 pH units, making them suitable to study a broad range of biophysical phenomena, especially at the negatively charged lipid bilayer surfaces. The rationale for selecting proper electrostatically neutral interface for probe calibration, and examples of lipid bilayer surface potential studies, are also described. © 2015 Elsevier Inc. All rights reserved.

The roles of fluid motion and other transport phenomena in the morphology of materials

NASA Technical Reports Server (NTRS)

Saville, D. A.

1993-01-01

Two crystallization problems were studied: the growth of protein crystals, in particular the influence of colloidal forces and convection, and the influence of interface resistance on the growth of dendritic crystals. The protein study involved both experimental and theoretical work; the work of dendrites was entirely theoretical. In the study of protein crystallization, experiments were carried out where crystals were grown in the presence and absence of natural convection. No evidence was found that convection retards crystal growth. The theoretical study focused on the influence of colloidal forces (electrostatic and London-van der Waals) on the interaction between a protein molecule and a flat crystal surface. It was shown that the interaction is extremely sensitive to colloidal forces and that electrostatic interactions play a strong role in deciding whether or not a molecule will find a favorable site for adsorption. In the study of dendritic growth, the role of an interfacial resistance on the selection processes was examined. Using a computational scheme, it was found that the selected velocity is strongly dependent on the magnitude of the interfacial resistance to heat transfer. This is a possible explanation for discrepancies between the theoretical and experimental results on succinonitrile.

Multiscale geometric modeling of macromolecules II: Lagrangian representation

PubMed Central

Feng, Xin; Xia, Kelin; Chen, Zhan; Tong, Yiying; Wei, Guo-Wei

2013-01-01

Geometric modeling of biomolecules plays an essential role in the conceptualization of biolmolecular structure, function, dynamics and transport. Qualitatively, geometric modeling offers a basis for molecular visualization, which is crucial for the understanding of molecular structure and interactions. Quantitatively, geometric modeling bridges the gap between molecular information, such as that from X-ray, NMR and cryo-EM, and theoretical/mathematical models, such as molecular dynamics, the Poisson-Boltzmann equation and the Nernst-Planck equation. In this work, we present a family of variational multiscale geometric models for macromolecular systems. Our models are able to combine multiresolution geometric modeling with multiscale electrostatic modeling in a unified variational framework. We discuss a suite of techniques for molecular surface generation, molecular surface meshing, molecular volumetric meshing, and the estimation of Hadwiger’s functionals. Emphasis is given to the multiresolution representations of biomolecules and the associated multiscale electrostatic analyses as well as multiresolution curvature characterizations. The resulting fine resolution representations of a biomolecular system enable the detailed analysis of solvent-solute interaction, and ion channel dynamics, while our coarse resolution representations highlight the compatibility of protein-ligand bindings and possibility of protein-protein interactions. PMID:23813599

Time-Dependent Solid State Polymorphism of a Series of Donor-Acceptor Dyads

PubMed Central

Peebles, Cameron; Alvey, Paul M.; Lynch, Vincent; Iverson, Brent L.

2014-01-01

In order to exploit the use of favorable electrostatic interactions between aromatic units in directing the assembly of donor-acceptor (D-A) dyads, the present work examines the ability of conjugated aromatic D-A dyads with symmetric side chains to exhibit solid-state polymorphism as a function of time during the solid formation process. Four such dyads were synthesized and their packing in the solid-state from either slower (10-20 days) or faster (1-2 days) evaporation from solvent was investigated using single crystal X-ray analysis and powder X-ray diffraction. Two of the dyads exhibited tail-to-tail (A-A) packing upon slower evaporation from solvent and head-to-tail (D-A) packing upon faster evaporation from solvent. A combination of single crystal analysis and XRD patterns were used to create models wherein a packing model for the other two dyads is proposed. Our findings suggest that while side chain interactions in asymmetric aromatic dyads can play an important role in enforcing segregated D-A dyad assembly, slowly evaporating symmetrically substituted aromatic dyads allows for favorable electrostatic interactions between the aromatic moieties to facilitate the organization of the dyads in the solid-state. PMID:24678269

The roles of fluid motion and other transport phenomena in the morphology of materials

NASA Astrophysics Data System (ADS)

Saville, D. A.

1993-11-01

Two crystallization problems were studied: the growth of protein crystals, in particular the influence of colloidal forces and convection, and the influence of interface resistance on the growth of dendritic crystals. The protein study involved both experimental and theoretical work; the work of dendrites was entirely theoretical. In the study of protein crystallization, experiments were carried out where crystals were grown in the presence and absence of natural convection. No evidence was found that convection retards crystal growth. The theoretical study focused on the influence of colloidal forces (electrostatic and London-van der Waals) on the interaction between a protein molecule and a flat crystal surface. It was shown that the interaction is extremely sensitive to colloidal forces and that electrostatic interactions play a strong role in deciding whether or not a molecule will find a favorable site for adsorption. In the study of dendritic growth, the role of an interfacial resistance on the selection processes was examined. Using a computational scheme, it was found that the selected velocity is strongly dependent on the magnitude of the interfacial resistance to heat transfer. This is a possible explanation for discrepancies between the theoretical and experimental results on succinonitrile.

Interaction-component analysis of the effects of urea and its alkylated derivatives on the structure of T4-lysozyme

NASA Astrophysics Data System (ADS)

Yamamori, Yu; Matubayasi, Nobuyuki

2017-06-01

The effects of urea and its alkylated derivatives on the structure of T4-lysozyme were analyzed from the standpoint of energetics. Molecular dynamics simulations were conducted with explicit solvent, and the energy-representation method was employed to compute the free energy of transfer of the protein from pure-water solvent to the mixed solvents of water with urea, methylurea, 1,1-dimethylurea, and isopropylurea. Through the decomposition of the transfer free energy into the cosolvent and water contributions, it was observed that the former is partially cancelled by the latter and governs the total free energy of transfer. To determine the interaction component responsible for the transfer energetics, the correlations of the transfer free energy were also examined against the change in the solute-solvent interaction energy upon transfer and the corresponding changes in the electrostatic, van der Waals, and excluded-volume components. It was then found over the set of protein structures ranging from native to (partially) unfolded ones that the transfer free energy changes in parallel with the van der Waals component even when the cosolvent is alkylated. The electrostatic and excluded-volume components play minor roles in the structure modification of the protein, and the denaturing ability of alkylurea is brought by the van der Waals interaction.

Electrostatic study of Alanine mutational effects on transcription: application to GATA-3:DNA interaction complex.

PubMed

El-Assaad, Atlal; Dawy, Zaher; Nemer, Georges

2015-01-01

Protein-DNA interaction is of fundamental importance in molecular biology, playing roles in functions as diverse as DNA transcription, DNA structure formation, and DNA repair. Protein-DNA association is also important in medicine; understanding Protein-DNA binding kinetics can assist in identifying disease root causes which can contribute to drug development. In this perspective, this work focuses on the transcription process by the GATA Transcription Factor (TF). GATA TF binds to DNA promoter region represented by `G,A,T,A' nucleotides sequence, and initiates transcription of target genes. When proper regulation fails due to some mutations on the GATA TF protein sequence or on the DNA promoter sequence (weak promoter), deregulation of the target genes might lead to various disorders. In this study, we aim to understand the electrostatic mechanism behind GATA TF and DNA promoter interactions, in order to predict Protein-DNA binding in the presence of mutations, while elaborating on non-covalent binding kinetics. To generate a family of mutants for the GATA:DNA complex, we replaced every charged amino acid, one at a time, with a neutral amino acid like Alanine (Ala). We then applied Poisson-Boltzmann electrostatic calculations feeding into free energy calculations, for each mutation. These calculations delineate the contribution to binding from each Ala-replaced amino acid in the GATA:DNA interaction. After analyzing the obtained data in view of a two-step model, we are able to identify potential key amino acids in binding. Finally, we applied the model to GATA-3:DNA (crystal structure with PDB-ID: 3DFV) binding complex and validated it against experimental results from the literature.

Anomalous Ground State of the Electrons in Nano-confined Water

DTIC Science & Technology

2016-06-13

confined water system, Nafion, is so different from that of bulk water that the weakly electrostatically interacting molecule model of water is clearly...assume that water is made up molecules weakly interacting(on the scale of the zero point bond energy~.2eV) electrostatically with its neighbors2-3. In an...not possible for a collection of molecules interacting weakly electrostatically . These changes in the spatial distribution of valence electrons in

Mechanism of the formation of the RecA-ssDNA nucleoprotein filament structure: a coarse-grained approach.

PubMed

Mukherjee, Goutam; Pal, Arumay; Levy, Yaakov

2017-11-21

In prokaryotes, the RecA protein catalyzes the repair and strand exchange of double-stranded DNA. RecA binds to single-stranded DNA (ssDNA) and forms a presynaptic complex in which the protein polymerizes around the ssDNA to form a right-handed helical nucleoprotein filament structure. In the present work, the mechanism for the formation of the RecA-ssDNA filament structure is modeled using coarse-grained molecular dynamics simulations. Information from the X-ray structure was used to model the protein itself but not its interactions; the interactions between the protein and the ssDNA were modeled solely by electrostatic, aromatic, and repulsive energies. For the present study, the monomeric, dimeric, and trimeric units of RecA and 4, 8, and 11 NT-long ssDNA, respectively, were studied. Our results indicate that monomeric RecA is not sufficient for nucleoprotein filament formation; rather, dimeric RecA is the elementary binding unit, with higher multimeric units of RecA facilitating filament formation. Our results reveal that loop region flexibility at the primary binding site of RecA is essential for it to bind the incoming ssDNA, that the aromatic residues present in the loop region play an important role in ssDNA binding, and that ATP may play a role in guiding the ssDNA by changing the electrostatic potential of the RecA protein.

Electrostatics in pharmaceutical aerosols for inhalation.

PubMed

Wong, Jennifer; Chan, Hak-Kim; Kwok, Philip Chi Lip

2013-08-01

Electrostatics continues to play an important role in pharmaceutical aerosols for inhalation. Despite its ubiquitous nature, the charging process is complex and not well understood. Nonetheless, significant advances in the past few years continue to improve understanding and lead to better control of electrostatics. The purpose of this critical review is to present an overview of the literature, with an emphasis on how electrostatic charge can be useful in improving pulmonary drug delivery.

Inter-subunit electrostatic interactions in ferritin molecule: comparison with inter-molecular interactions in crystals

NASA Astrophysics Data System (ADS)

Takahashi, Takuya; Hogyoku, Michiru; Nagayama, Kuniaki

1996-10-01

We evaluated the contribution of electrostatic interactions to the stability of macromolecular assembly in a horse L ferritin molecule composed of 24 subunits and the three-dimensional crystal of the ferritin molecules with numerical calculation of Poisson-Boltzmann equation based on dielectric model. The calculation showed that the electrostatic energy both favors the assembly of the 24 subunits and the crystalline assembly of the ferritin molecules (i.e., 24-mers). Short-range interactions less than 5 Å such as salt bridges and hydrogen bonds were important for both the subunit assembly and the crystalline assembly. To elucidate the strong stabilization by electrostatic interactions in both the ferritin 24-mer and its crystal, we analyzed the contribution of individual atoms. It revealed that the stabilization was arising from buried salt bridges or hydrogen bonds, which yielded more than 5 kcal/mol in some interactions. These large electrostatic stabilization and also the unexpected small ionic strength dependence was different from those of bovine pancreatic trypsin inhibitor (BPTI) orthorhombic and pig-insulin cubic crystals previously calculated. We also evaluated changes of the accessible surface area (ASA) and hydration free energy in accordance with the process of the subunit assembly. The change of hydration free energy, which was very large (i.e. ˜ + 100 kcal/mol/subunit) and unfavorable for the assembly, was proportional to the electrostatic hydration energy (i.e. Born energy change in hydration process). Hydrophobic groups were likely to appear more frequently than hydrophilic groups at the subunit interfaces. These results suggest that the molecular structure of the ferritin 24-mer and the crystal structure of the 24-mers were both stabilized by local electrostatic interactions, in particular. We view protein crystals as an extension of the protein oligomer to an infinite number of subunits association.

The importance of cantilever dynamics in the interpretation of Kelvin probe force microscopy.

PubMed

Satzinger, Kevin J; Brown, Keith A; Westervelt, Robert M

2012-09-15

A realistic interpretation of the measured contact potential difference (CPD) in Kelvin probe force microscopy (KPFM) is crucial in order to extract meaningful information about the sample. Central to this interpretation is a method to include contributions from the macroscopic cantilever arm, as well as the cone and sharp tip of a KPFM probe. Here, three models of the electrostatic interaction between a KPFM probe and a sample are tested through an electrostatic simulation and compared with experiment. In contrast with previous studies that treat the KPFM cantilever as a rigid object, we allow the cantilever to bend and rotate; accounting for cantilever bending provides the closest agreement between theory and experiment. We demonstrate that cantilever dynamics play a major role in CPD measurements and provide a simulation technique to explore this phenomenon.

Cooperative Effects of Zwitterionic-Ionic Surfactant Mixtures on the Interfacial Water Structure Revealed by Sum Frequency Generation Vibrational Spectroscopy.

PubMed

Pan, Xuecong; Yang, Fangyuan; Chen, Shunli; Zhu, Xuefeng; Wang, Chuanyi

2018-05-08

Cooperative effects of a series of equimolar binary zwitterionic-ionic surfactant mixtures on the interfacial water structure at the air-water interfaces have been studied by sum frequency generation vibrational spectroscopy (SFG-VS). For zwitterionic surfactant palmityl sulfobetaine (SNC 16 ), anionic surfactant sodium hexadecyl sulfate (SHS), and cationic surfactant cetyltrimethylammonium bromide (CTAB) with the same length of alkyl chain, significantly enhanced ordering of interfacial water molecules was observed for the zwitterionic-anionic surfactant mixtures SNC 16 -SHS, indicating that SNC 16 interacts more strongly with SHS than with CTAB because of the strong headgroup-headgroup electrostatic attraction for SNC 16 -SHS. Meanwhile, the SFG amplitude ratio of methyl and methylene symmetric stretching modes was used to verify the stronger interaction between SNC 16 and SHS. The conformational order indicator increased from 0.64 for SNC 16 to 7.17 for SNC 16 -SHS but only 0.94 for SNC 16 -CTAB. In addition, another anionic surfactant sodium dodecyl sulfate (SDS) was introduced to study the influence of chain-chain interaction. Decreased SFG amplitude of interfacial water molecules for SNC 16 -SDS was observed. Therefore, both the headgroup-headgroup electrostatic interaction and chain-chain van der Waals attractive interaction of the surfactants play an important role in enhancing the ordering of interfacial water molecules. The results provided experimental and theoretical bases for practical applications of the surfactants.

Simulation study of charged nanoparticles confined in a rectangular tube with discrete wall charges.

PubMed

Yuet, Pak K

2006-03-28

The development of novel nanomaterials has been a subject of intense interest in recent years. An interesting structure among these materials is the so-called "pea pods" (i.e., nanoparticles confined in nanotubes). To facilitate the development and commercialization of these materials, it is important that we have an in-depth understanding of their behavior. The study of confined charged particles is particularly challenging because of the long-ranged nature of electrostatic interaction, and both interparticle and particle-confinement interactions are likely to play a role in determining the system behavior. The primary objective of this study is to develop a better understanding of the behavior of charged nanoparticles in a charged tubular confinement using Monte Carlo simulation, with particular focus on the effect of electrostatic interactions on the structure of the particles. Simulation results have shown that (i) the structuring of confined particles is associated with the asymmetry of the long-ranged interaction and (ii) factors such as confinement geometry and particle charge and size asymmetry can be manipulated to produce different particle structures. The present study represents the first step in an attempt to gain further insight into the behavior of confined nanosystems, with the ultimate objective of exploiting these characteristics, particularly the interactions between the confined particles and their external environment, in developing novel nanomaterials.

Red-Shifting versus Blue-Shifting Hydrogen Bonds: Perspective from Ab Initio Valence Bond Theory.

PubMed

Chang, Xin; Zhang, Yang; Weng, Xinzhen; Su, Peifeng; Wu, Wei; Mo, Yirong

2016-05-05

Both proper, red-shifting and improper, blue-shifting hydrogen bonds have been well-recognized with enormous experimental and computational studies. The current consensus is that there is no difference in nature between these two kinds of hydrogen bonds, where the electrostatic interaction dominates. Since most if not all the computational studies are based on molecular orbital theory, it would be interesting to gain insight into the hydrogen bonds with modern valence bond (VB) theory. In this work, we performed ab initio VBSCF computations on a series of hydrogen-bonding systems, where the sole hydrogen bond donor CF3H interacts with ten hydrogen bond acceptors Y (═NH2CH3, NH3, NH2Cl, OH(-), H2O, CH3OH, (CH3)2O, F(-), HF, or CH3F). This series includes four red-shifting and six blue-shifting hydrogen bonds. Consistent with existing findings in literature, VB-based energy decomposition analyses show that electrostatic interaction plays the dominating role and polarization plays the secondary role in all these hydrogen-bonding systems, and the charge transfer interaction, which denotes the hyperconjugation effect, contributes only slightly to the total interaction energy. As VB theory describes any real chemical bond in terms of pure covalent and ionic structures, our fragment interaction analysis reveals that with the approaching of a hydrogen bond acceptor Y, the covalent state of the F3C-H bond tends to blue-shift, due to the strong repulsion between the hydrogen atom and Y. In contrast, the ionic state F3C(-) H(+) leads to the red-shifting of the C-H vibrational frequency, owing to the attraction between the proton and Y. Thus, the relative weights of the covalent and ionic structures essentially determine the direction of frequency change. Indeed, we find the correlation between the structural weights and vibrational frequency changes.

The measured and calculated affinity of methyl and methoxy substituted benzoquinones for the QA site of bacterial reaction centers

PubMed Central

Zheng, Zhong; Dutton, P. Leslie; Gunner, M. R.

2010-01-01

Quinones play important roles in mitochondrial and photosynthetic energy conversion acting as intramembrane, mobile electron and proton carriers between catalytic sites in various electron transfer proteins. They display different affinity, selectivity, functionality and exchange dynamics in different binding sites. The computational analysis of quinone binding sheds light on the requirements for quinone affinity and specificity. The affinities of ten oxidized, neutral benzoquinones (BQs) were measured for the high affinity QA site in the detergent solubilized Rhodobacter sphaeroides bacterial photosynthetic reaction center. Multi-Conformation Continuum Electrostatics (MCCE) was then used to calculate their relative binding free energies by Grand Canonical Monte Carlo sampling with a rigid protein backbone, flexible ligand and side chain positions and protonation states. Van der Waals and torsion energies, Poisson-Boltzmann continuum electrostatics and accessible surface area dependent ligand-solvent interactions are considered. An initial, single cycle of GROMACS backbone optimization improves the match with experiment as do coupled ligand and side chain motions. The calculations match experiment with an RMSD of 2.29 and a slope of 1.28. The affinities are dominated by favorable protein-ligand van der Waals rather than electrostatic interactions. Each quinone appears in a closely clustered set of positions. Methyl and methoxy groups move into the same positions as found for the native quinone. Difficulties putting methyls into methoxy sites are observed. Calculations using an SAS dependent implicit van der Waals interaction smoothed out small clashes, providing a better match to experiment with a RMSD of 0.77 and a slope of 0.97. PMID:20607696

The electrostatic interaction between interfacial colloidal particles

NASA Astrophysics Data System (ADS)

Hurd, A. J.

1985-11-01

The electrostatic interaction between charged, colloidal particles trapped at an air-water interface is considered using linearised Poisson-Boltzmann results for point particles. In addition to the expected screened-Coulomb contribution, which decays exponentially, an algebraic dipole-dipole interaction occurs that may account for long-range interactions in interfacial colloidal systems.

Biochemical enhancement of transdermal delivery with magainin peptide: modification of electrostatic interactions by changing pH.

PubMed

Kim, Yeu-Chun; Late, Sameer; Banga, Ajay K; Ludovice, Peter J; Prausnitz, Mark R

2008-10-01

Magainin is a naturally occurring, pore-forming peptide that has recently been shown to increase skin permeability. This study tested the hypothesis that electrostatic forces between magainin peptides and drugs mediate drug transport across the skin. Electrostatic interaction between positively charged magainin and a negatively charged model drug, fluorescein, was attractive at pH 7.4 and resulted in a 35-fold increase in delivery across human epidermis in vitro when formulated with 2% N-lauroylsarcosine in 50% ethanol. Increasing to pH 10 or 11 largely neutralized magainin's charge, which eliminated enhancement due to magainin. Shielding electrostatic interactions with 1-2M NaCl solution similarly eliminated enhancement. Showing the opposite dependence on pH, electrostatic interaction between magainin and a positively charged anti-nausea drug, granisetron, was largely neutralized at pH 10 and resulted in a 92-fold increase in transdermal delivery. Decreasing to pH 5 increased magainin's positive charge, which repelled granisetron and progressively decreased transdermal flux. Circular dichroism analysis, multi-photon microscopy, and FTIR spectroscopy showed no significant pH effect on magainin secondary structure, magainin deposition in stratum corneum, or stratum corneum lipid order, respectively. We conclude that magainin increases transdermal delivery by a mechanism involving electrostatic interaction between magainin peptides and drugs.

Biochemical enhancement of transdermal delivery with magainin peptide: Modification of electrostatic interactions by changing pH

PubMed Central

Kim, Yeu-Chun; Late, Sameer; Banga, Ajay K.; Ludovice, Peter J.; Prausnitz, Mark R.

2008-01-01

Magainin is a naturally occurring, pore-forming peptide that has recently been shown to increase skin permeability. This study tested the hypothesis that electrostatic forces between magainin peptides and drugs mediate drug transport across the skin. Electrostatic interaction between positively charged magainin and a negatively charged model drug, fluorescein, was attractive at pH 7.4 and resulted in a 35 fold increase in delivery across human epidermis in vitro when formulated with 2% N-lauroylsarcosine in 50% ethanol. Increasing to pH 10 or 11 largely neutralized magainin’s charge, which eliminated enhancement due to magainin. Shielding electrostatic interactions with 1–2 M NaCl solution similarly eliminated enhancement. Showing the opposite dependence on pH, electrostatic interaction between magainin and a positively charged anti-nausea drug, granisetron, was largely neutralized at pH 10 and resulted in a 59 fold increase in transdermal delivery. Decreasing to pH 5 increased magainin’s positive charge, which repelled granisetron and progressively decreased transdermal flux. Circular dichroism analysis, multi-photon microscopy, and FTIR spectroscopy showed no significant pH effect on magainin secondary structure, magainin deposition in stratum corneum, or stratum corneum lipid order, respectively. We conclude that magainin increases transdermal delivery by a mechanism involving electrostatic interaction between magainin peptides and drugs. PMID:18601987

Electrostatic interaction based approach to thrombin detection by surface-enhanced Raman spectroscopy.

PubMed

Hu, Juan; Zheng, Peng-Cheng; Jiang, Jian-Hui; Shen, Guo-Li; Yu, Ru-Qin; Liu, Guo-Kun

2009-01-01

We have developed an electrostatic interaction based biosensor for thrombin detection using surface-enhanced Raman spectroscopy (SERS). This method utilized the electrostatic interaction between capture (thrombin aptamer) and probe (crystal violet, CV) molecules. The specific interaction between thrombin and aptamer could weaken the electrostatic barrier effect from the negative charged aptamer SAMs to the diffusion process of the positively charged CV from the bulk solution to the Au nanoparticle surface. Therefore, the more the bound thrombin, the more the CV molecules near the Au nanoparticle surface and the stronger the observed Raman signal of CV, provided the Raman detections were set at the same time point for each case. This procedure presented a highly specific selectivity and a linear detection of thrombin in the range from 0.1 nM to 10 nM with a detection limit of about 20 pM and realized the thrombin detection in human blood serum solution directly. The electrostatic interaction based technique provides an easy and fast-responding optical platform for a "signal-on" detection of proteins, which might be applicable for the real time assay of proteins.

The Effect of Lipopolysaccharide Core Oligosaccharide Size on the Electrostatic Binding of Antimicrobial Proteins to Models of the Gram Negative Bacterial Outer Membrane

PubMed Central

2016-01-01

Understanding the electrostatic interactions between bacterial membranes and exogenous proteins is crucial to designing effective antimicrobial agents against Gram-negative bacteria. Here we study, using neutron reflecometry under multiple isotopic contrast conditions, the role of the uncharged sugar groups in the outer core region of lipopolysaccharide (LPS) in protecting the phosphate-rich inner core region from electrostatic interactions with antimicrobial proteins. Models of the asymmetric Gram negative outer membrane on silicon were prepared with phopshatidylcholine (PC) in the inner leaflet (closest to the silicon), whereas rough LPS was used to form the outer leaflet (facing the bulk solution). We show how salt concentration can be used to reversibly alter the binding affinity of a protein antibiotic colicin N (ColN) to the anionic LPS confirming that the interaction is electrostatic in nature. By examining the interaction of ColN with two rough LPS types with different-sized core oligosaccharide regions we demonstrate the role of uncharged sugars in blocking short-range electrostatic interactions between the cationic antibiotics and the vulnerable anionic phosphate groups. PMID:27003358

Ionizable Nitroxides for Studying Local Electrostatic Properties of Lipid Bilayers and Protein Systems by EPR

PubMed Central

Voinov, Maxim A.; Smirnov, Alex I.

2016-01-01

Electrostatic interactions are known to play one of the major roles in the myriad of biochemical and biophysical processes. In this Chapter we describe biophysical methods to probe local electrostatic potentials of proteins and lipid bilayer systems that is based on an observation of reversible protonation of nitroxides by EPR. Two types of the electrostatic probes are discussed. The first one includes methanethiosulfonate derivatives of protonatable nitroxides that could be used for highly specific covalent modification of the cysteine’s sulfhydryl groups. Such spin labels are very similar in magnetic parameters and chemical properties to conventional MTSL making them suitable for studying local electrostatic properties of protein-lipid interfaces. The second type of EPR probes is designed as spin-labeled phospholipids having a protonatable nitroxide tethered to the polar head group. The probes of both types report on their ionization state through changes in magnetic parameters and a degree of rotational averaging, thus, allowing one to determine the electrostatic contribution to the interfacial pKa of the nitroxide, and, therefore, determining the local electrostatic potential. Due to their small molecular volume these probes cause a minimal perturbation to the protein or lipid system while covalent attachment secure the position of the reporter nitroxides. Experimental procedures to characterize and calibrate these probes by EPR and also the methods to analyze the EPR spectra by least-squares simulations are also outlined. The ionizable nitroxide labels and the nitroxide-labeled phospholipids described so far cover an exceptionally wide pH range from ca. 2.5 to 7.0 pH units making them suitable to study a broad range of biophysical phenomena especially at the negatively charged lipid bilayer surfaces. The rationale for selecting proper electrostatically neutral interface for calibrating such probes and example of studying surface potential of lipid bilayer is also described. PMID:26477252

Electrostatic contribution to the persistence length of a semiflexible dipolar chain.

PubMed

Podgornik, Rudi

2004-09-01

We investigate the electrostatic contribution to the persistence length of a semiflexible polymer chain whose segments interact via a screened Debye-Hückel dipolar interaction potential. We derive the expressions for the renormalized persistence length on the level of a 1/D-expansion method already successfully used in other contexts of polyelectrolye physics. We investigate different limiting forms of the renormalized persistence length of the dipolar chain and show that, in, general, it depends less strongly on the screening length than in the context of a monopolar chain. We show that for a dipolar chain the electrostatic persistence length in the same regime of the parameter phase space as the original Odijk-Skolnick-Fixman (OSF) form for a monopolar chain depends logarithmically on the screening length rather than quadratically. This can be understood solely on the basis of a swifter decay of the dipolar interactions with separation compared to the monopolar electrostatic interactions. We comment also on the general contribution of higher multipoles to the electrostatic renormalization of the bending rigidity.

DNA packaging in viral capsids with peptide arms.

PubMed

Cao, Qianqian; Bachmann, Michael

2017-01-18

Strong chain rigidity and electrostatic self-repulsion of packed double-stranded DNA in viruses require a molecular motor to pull the DNA into the capsid. However, what is the role of electrostatic interactions between different charged components in the packaging process? Though various theories and computer simulation models were developed for the understanding of viral assembly and packaging dynamics of the genome, long-range electrostatic interactions and capsid structure have typically been neglected or oversimplified. By means of molecular dynamics simulations, we explore the effects of electrostatic interactions on the packaging dynamics of DNA based on a coarse-grained DNA and capsid model by explicitly including peptide arms (PAs), linked to the inner surface of the capsid, and counterions. Our results indicate that the electrostatic interactions between PAs, DNA, and counterions have a significant influence on the packaging dynamics. We also find that the packed DNA conformations are largely affected by the structure of the PA layer, but the packaging rate is insensitive to the layer structure.

Protein-protein interfaces are vdW dominant with selective H-bonds and (or) electrostatics towards broad functional specificity.

PubMed

Nilofer, Christina; Sukhwal, Anshul; Mohanapriya, Arumugam; Kangueane, Pandjassarame

2017-01-01

Several catalysis, cellular regulation, immune function, cell wall assembly, transport, signaling and inhibition occur through Protein- Protein Interactions (PPI). This is possible with the formation of specific yet stable protein-protein interfaces. Therefore, it is of interest to understand its molecular principles using structural data in relation to known function. Several interface features have been documented using known X-ray structures of protein complexes since 1975. This has improved our understanding of the interface using structural features such as interface area, binding energy, hydrophobicity, relative hydrophobicity, salt bridges and hydrogen bonds. The strength of binding between two proteins is dependent on interface size (number of residues at the interface) and thus its corresponding interface area. It is known that large interfaces have high binding energy (sum of (van der Waals) vdW, H-bonds, electrostatics). However, the selective role played by each of these energy components and more especially that of vdW is not explicitly known. Therefore, it is important to document their individual role in known protein-protein structural complexes. It is of interest to relate interface size with vdW, H-bonds and electrostatic interactions at the interfaces of protein structural complexes with known function using statistical and multiple linear regression analysis methods to identify the prominent force. We used the manually curated non-redundant dataset of 278 hetero-dimeric protein structural complexes grouped using known functions by Sowmya et al. (2015) to gain additional insight to this phenomenon using a robust inter-atomic non-covalent interaction analyzing tool PPCheck (Anshul and Sowdhamini, 2015). This dataset consists of obligatory (enzymes, regulator, biological assembly), immune and nonobligatory (enzyme and regulator inhibitors) complexes. Results show that the total binding energy is more for large interfaces. However, this is not true for its individual energy factors. Analysis shows that vdW energies contribute to about 75% ± 11% on average among all complexes and it also increases with interface size (r2 ranging from 0.67 to 0.89 with p<0.01) at 95% confidence limit irrespective of molecular function. Thus, vdW is both dominant and proportional at the interface independent of molecular function. Nevertheless, H bond energy contributes to 15% ± 6.5% on average in these complexes. It also moderately increases with interface size (r2 ranging from 0.43 to 0.61 with p<0.01) only among obligatory and immune complexes. Moreover, there is about 11.3% ± 8.7% contribution by electrostatic energy. It increases with interface size specifically among non-obligatory regulator-inhibitors (r2 = 0.44). It is implied that both H-bonds and electrostatics are neither dominant nor proportional at the interface. Nonetheless, their presence cannot be ignored in binding. Therefore, H-bonds and (or) electrostatic energy having specific role for improved stability in complexes is implied. Thus, vdW is common at the interface stabilized further with selective H-bonds and (or) electrostatic interactions at an atomic level in almost all complexes. Comparison of this observation with residue level analysis of the interface is compelling. The role by H-bonds (14.83% ± 6.5% and r2 = 0.61 with p<0.01) among obligatory and electrostatic energy (8.8% ± 4.77% and r2 = 0.63 with p <0.01) among non-obligatory complexes within interfaces (class A) having more non-polar residues than surface is influencing our inference. However, interfaces (class B) having less non-polar residues than surface show 1.5 fold more electrostatic energy on average. The interpretation of the interface using inter-atomic (vdW, H-bonds, electrostatic) interactions combined with inter-residue predominance (class A and class B) in relation to known function is the key to reveal its molecular principles with new challenges.

Long range Debye-Hückel correction for computation of grid-based electrostatic forces between biomacromolecules

PubMed Central

2014-01-01

Background Brownian dynamics (BD) simulations can be used to study very large molecular systems, such as models of the intracellular environment, using atomic-detail structures. Such simulations require strategies to contain the computational costs, especially for the computation of interaction forces and energies. A common approach is to compute interaction forces between macromolecules by precomputing their interaction potentials on three-dimensional discretized grids. For long-range interactions, such as electrostatics, grid-based methods are subject to finite size errors. We describe here the implementation of a Debye-Hückel correction to the grid-based electrostatic potential used in the SDA BD simulation software that was applied to simulate solutions of bovine serum albumin and of hen egg white lysozyme. Results We found that the inclusion of the long-range electrostatic correction increased the accuracy of both the protein-protein interaction profiles and the protein diffusion coefficients at low ionic strength. Conclusions An advantage of this method is the low additional computational cost required to treat long-range electrostatic interactions in large biomacromolecular systems. Moreover, the implementation described here for BD simulations of protein solutions can also be applied in implicit solvent molecular dynamics simulations that make use of gridded interaction potentials. PMID:25045516

Mapping the surface charge distribution of amyloid fibril

NASA Astrophysics Data System (ADS)

Lee, Gyudo; Lee, Wonseok; Lee, Hyungbeen; Woo Lee, Sang; Sung Yoon, Dae; Eom, Kilho; Kwon, Taeyun

2012-07-01

It is of high importance to measure and map the surface charge distribution of amyloids, since electrostatic interaction between amyloidogenic proteins and biomolecules plays a vital role in amyloidogenesis. In this work, we have measured and mapped the surface charge distributions of amyloids (i.e., β-lactoglobulin fibril) using Kelvin probe force microscopy. It is shown that the surface charge distribution is highly dependent on the conformation of amyloids (e.g., the helical pitch of amyloid fibrils) as well as the pH of a solvent.

BIOPHYSICS. Comment on "Extreme electric fields power catalysis in the active site of ketosteroid isomerase".

PubMed

Chen, Deliang; Savidge, Tor

2015-08-28

Fried et al. (Reports, 19 December 2014, p. 1510) demonstrate electric field-dependent acceleration of biological catalysis using ketosteroid isomerase as a prototypic example. These findings were not extended to aqueous solution because water by itself has field fluctuations that are too large and fast to provide a catalytic effect. Given physiological context, when water electrostatic interactions are considered, electric fields play a less important role in the catalysis. Copyright © 2015, American Association for the Advancement of Science.

Investigating protein-protein interaction surfaces using a reduced stereochemical and electrostatic model.

PubMed

Warwicker, J

1989-03-20

A method of calculating the electrostatic potential energy between two molecules, using finite difference potential, is presented. A reduced charge set is used so that the interaction energy can be calculated as the two static molecules explore their full six-dimensional configurational space. The energies are contoured over surfaces fixed to each molecule with an interactive computer graphics program. For two crystal structures (trypsin-trypsin inhibitor and anti-lysozyme Fab-lysozyme), it is found that the complex corresponds to highly favourable interacting regions in the contour plots. These matches arise from a small number of protruding basic residues interacting with enhanced negative potential in each case. The redox pair cytochrome c peroxidase-cytochrome c exhibits an extensive favourably interacting surface within which a possible electron transfer complex may be defined by an increased electrostatic complementarity, but a decreased electrostatic energy. A possible substrate transfer configuration for the glycolytic enzyme pair glyceraldehyde phosphate dehydrogenase-phosphoglycerate kinase is presented.

Optimization of binding electrostatics: Charge complementarity in the barnase-barstar protein complex

PubMed Central

lee, Lee-Peng; Tidor, Bruce

2001-01-01

Theoretical and experimental studies have shown that the large desolvation penalty required for polar and charged groups frequently precludes their involvement in electrostatic interactions that contribute strongly to net stability in the folding or binding of proteins in aqueous solution near room temperature. We have previously developed a theoretical framework for computing optimized electrostatic interactions and illustrated use of the algorithm with simplified geometries. Given a receptor and model assumptions, the method computes the ligand-charge distribution that provides the most favorable balance of desolvation and interaction effects on binding. In this paper the method has been extended to treat complexes using actual molecular shapes. The barnase-barstar protein complex was investigated with barnase treated as a target receptor. The atomic point charges of barstar were varied to optimize the electrostatic binding free energy. Barnase and natural barstar form a tight complex (Kd ∼ 10−14 M) with many charged and polar groups near the interface that make this a particularly relevant system for investigating the role of electrostatic effects on binding. The results show that sets of barstar charges (resulting from optimization with different constraints) can be found that give rise to relatively large predicted improvements in electrostatic binding free energy. Principles for enhancing the effect of electrostatic interactions in molecular binding in aqueous environments are discussed in light of the optima. Our findings suggest that, in general, the enhancements in electrostatic binding free energy resulting from modification of polar and charged groups can be substantial. Moreover, a recently proposed definition of electrostatic complementarity is shown to be a useful tool for examining binding interfaces. Finally, calculational results suggest that wild-type barstar is closer to being affinity optimized than is barnase for their mutual binding, consistent with the known roles of these proteins. PMID:11266622

Defining protein electrostatic recognition processes

NASA Astrophysics Data System (ADS)

Getzoff, Elizabeth D.; Roberts, Victoria A.

The objective is to elucidate the nature of electrostatic forces controlling protein recognition processes by using a tightly coupled computational and interactive computer graphics approach. The TURNIP program was developed to determine the most favorable precollision orientations for two molecules by systematic search of all orientations and evaluation of the resulting electrostatic interactions. TURNIP was applied to the transient interaction between two electron transfer metalloproteins, plastocyanin and cytochrome c. The results suggest that the productive electron-transfer complex involves interaction of the positive region of cytochrome c with the negative patch of plastocyanin, consistent with experimental data. Application of TURNIP to the formation of the stable complex between the HyHEL-5 antibody and its protein antigen lysozyme showed that long-distance electrostatic forces guide lysozyme toward the HyHEL-5 binding site, but do not fine tune its orientation. Determination of docked antigen/antibody complexes requires including steric as well as electrostatic interactions, as was done for the U10 mutant of the anti-phosphorylcholine antibody S107. The graphics program Flex, a convenient desktop workstation program for visualizing molecular dynamics and normal mode motions, was enhanced. Flex now has a user interface and was rewritten to use standard graphics libraries, so as to run on most desktop workstations.

Understanding and Manipulating Electrostatic Fields at the Protein-Protein Interface Using Vibrational Spectroscopy and Continuum Electrostatics Calculations.

PubMed

Ritchie, Andrew W; Webb, Lauren J

2015-11-05

Biological function emerges in large part from the interactions of biomacromolecules in the complex and dynamic environment of the living cell. For this reason, macromolecular interactions in biological systems are now a major focus of interest throughout the biochemical and biophysical communities. The affinity and specificity of macromolecular interactions are the result of both structural and electrostatic factors. Significant advances have been made in characterizing structural features of stable protein-protein interfaces through the techniques of modern structural biology, but much less is understood about how electrostatic factors promote and stabilize specific functional macromolecular interactions over all possible choices presented to a given molecule in a crowded environment. In this Feature Article, we describe how vibrational Stark effect (VSE) spectroscopy is being applied to measure electrostatic fields at protein-protein interfaces, focusing on measurements of guanosine triphosphate (GTP)-binding proteins of the Ras superfamily binding with structurally related but functionally distinct downstream effector proteins. In VSE spectroscopy, spectral shifts of a probe oscillator's energy are related directly to that probe's local electrostatic environment. By performing this experiment repeatedly throughout a protein-protein interface, an experimental map of measured electrostatic fields generated at that interface is determined. These data can be used to rationalize selective binding of similarly structured proteins in both in vitro and in vivo environments. Furthermore, these data can be used to compare to computational predictions of electrostatic fields to explore the level of simulation detail that is necessary to accurately predict our experimental findings.

Electrostatic Rate Enhancement and Transient Complex of Protein-Protein Association

PubMed Central

Alsallaq, Ramzi; Zhou, Huan-Xiang

2012-01-01

The association of two proteins is bounded by the rate at which they, via diffusion, find each other while in appropriate relative orientations. Orientational constraints restrict this rate to ~105 – 106 M−1s−1. Proteins with higher association rates generally have complementary electrostatic surfaces; proteins with lower association rates generally are slowed down by conformational changes upon complex formation. Previous studies (Zhou, Biophys. J. 1997;73:2441–2445) have shown that electrostatic enhancement of the diffusion-limited association rate can be accurately modeled by kD = kD0 exp(−*/ kBT), where kD and kD0 are the rates in the presence and absence of electrostatic interactions, respectively, * is the average electrostatic interaction energy in a “transient-complex” ensemble, and kBT is thermal energy. The transient-complex ensemble separates the bound state from the unbound state. Predictions of the transient-complex theory on four protein complexes were found to agree well with experiment when the electrostatic interaction energy was calculated with the linearized Poisson-Boltzmann (PB) equation (Alsallaq and Zhou, Structure 2007, 15:215–224). Here we show that the agreement is further improved when the nonlinear PB equation is used. These predictions are obtained with the dielectric boundary defined as the protein van der Waals surface. When the dielectric boundary is instead specified as the molecular surface, electrostatic interactions in the transient complex become repulsive and are thus predicted to retard association. Together these results demonstrate that the transient-complex theory is predictive of electrostatic rate enhancement and can help parameterize PB calculations. PMID:17932929

Effective Field Theory of Surface-mediated Forces in Soft Matter

NASA Astrophysics Data System (ADS)

Yolcu, Cem

We propose a field theoretic formalism for describing soft surfaces modified by the presence of inclusions. Examples include particles trapped at a fluid-fluid interface, proteins attached to (or embedded in) a biological membrane, etc. We derive the energy functional for near-flat surfaces by an effective field theory approach. The two disparate length scales, particle sizes and inter-particle separations, afford the expansion parameters for controlling the accuracy of the effective theory, which is arbitrary in principle. We consider the following two surface types: (i) one where tension determines the behavior, such as a fluid-fluid interface (referred to as a film), and (ii) one where bending-elasticity dominates (referred to as a membrane). We also restrict to rigid inclusions with a circular footprint, and discuss generalizations briefly. As a result of the localized constraints imposed on the surface by the inclusions, the free energy of the system depends on their spatial arrangement, i.e. forces arise between them. Such surface-mediated interactions are believed to play an important role in the aggregation behavior of colloidal particles at interfaces and proteins on membranes. The interaction free energy consists of two parts: (i) the ground-state of the surface determined by possible deformations imposed by the particles, and (ii) the fluctuation correction. The former is analogous to classical electrostatics with the height profile of the surface playing the role of the electrostatic potential, while the latter is analogous to the Casimir effect and originates from the mere presence of constraints. We compute both interactions in truncated expansions. The efficiency of the formalism allows us to predict, with remarkable ease, quite a few orders of subleading corrections to existing results which are only valid when the inclusions are infinitely far apart. We also found that the few previous studies on finite distance corrections were incomplete. In addition to pairwise additive interactions, we compute the leading behavior of several many-body interactions, as well as subleading corrections where the leading contribution was previously calculated.

Deconvolution of Raman spectroscopic signals for electrostatic, H-bonding, and inner-sphere interactions between ions and dimethyl phosphate in solution

PubMed Central

Christian, Eric L; Anderson, Vernon E.; Harris, Michael E

2011-01-01

Quantitative analysis of metal ion-phosphodiester interactions is a significant experimental challenge due to the complexities introduced by inner-sphere, outer-sphere (H-bonding with coordinated water), and electrostatic interactions that are difficult to isolate in solution studies. Here, we provide evidence that inner-sphere, H-bonding and electrostatic interactions between ions and dimethyl phosphate can be deconvoluted through peak fitting in the region of the Raman spectrum for the symmetric stretch of non-bridging phosphate oxygens (νsPO 2-). An approximation of the change in vibrational spectra due to different interaction modes is achieved using ions capable of all or a subset of the three forms of metal ion interaction. Contribution of electrostatic interactions to ion-induced changes to the Raman νsPO2- signal could be modeled by monitoring attenuation of νsPO2- in the presence of tetramethylammonium, while contribution of H-bonding and inner-sphere coordination could be approximated from the intensities of altered νsPO2- vibrational modes created by an interaction with ammonia, monovalent or divalent ions. A model is proposed in which discrete spectroscopic signals for inner-sphere, H-bonding, and electrostatic interactions are sufficient to account for the total observed change in νsPO2- signal due to interaction with a specific ion capable of all three modes of interaction. Importantly, the quantitative results are consistent with relative levels of coordination predicted from absolute electronegativity and absolute hardness of alkali and alkaline earth metals. PMID:21334281

Protein Adsorption and Deposition onto Microfiltration Membranes: The Role of Solute-Solid Interactions.

PubMed

Martínez; Martín; Prádanos; Calvo; Palacio; Hernández

2000-01-15

The mass of gamma-globulin fouling an Anodisc alumina membrane with a nominal pore diameter of 0.1 µm has been measured at several concentrations and pHs. This fouling resulted from filtering through the membrane in a continuous recirculation device. The low-concentration fouling can be attributed mainly to adsorption. The complete concentration dependence of fouling mass has been obtained and fitted to a Freundlich heterogeneous isotherm, from which the pH dependence of active fouling sites and energies has been also obtained. Adsorption is studied as a function of the electrostatic forces between the solute and the membrane. A sharp maximum in the adsorbed mass for zero electrostatic force is observed. At high concentrations, accumulation plays a relevant role at alkaline pH, as confirmed by flux decay experiments, retention measurements, and AFM (atomic force microscopy) pictures. Copyright 2000 Academic Press.

Electron Jet of Asymmetric Reconnection

NASA Technical Reports Server (NTRS)

Khotyaintsev, Yu. V.; Graham, D. B.; Norgren, C.; Eriksson, E.; Li, W.; Johlander, A.; Vaivads, A.; Andre, M.; Pritchett, P. L.; Retino, A.;

Linear and nonlinear interactions of an electron beam with oblique whistler and electrostatic waves in the magnetosphere

NASA Astrophysics Data System (ADS)

Zhang, Y. L.; Matsumoto, H.; Omura, Y.

1993-12-01

Both linear and nonlinear interactions between oblique whistler, electrostatic, quasi-upper hybrid mode waves and an electron beam are studied by linear analyses and electromagnetic particle simulations. In addition to a background cold plasma, we assumed a hot electron beam drifting along a static magnetic field. Growth rates of the oblique whistler, oblique electrostatic, and quasi-upper hybrid instabilities were first calculated. We found that there are four kinds of unstable mode waves for parallel and oblique propagations. They are the electromagnetic whistler mode wave (WW1), the electrostatic whistler mode wave (WW2), the electrostatic mode wave (ESW), and the quasi-upper hybrid mode wave (UHW). A possible mechanism is proposed to explain the satellite observations of whistler mode chorus and accompanied electrostatic waves, whose amplitudes are sometimes modulated at the chorus frequency.

webPIPSA: a web server for the comparison of protein interaction properties

PubMed Central

Richter, Stefan; Wenzel, Anne; Stein, Matthias; Gabdoulline, Razif R.; Wade, Rebecca C.

2008-01-01

Protein molecular interaction fields are key determinants of protein functionality. PIPSA (Protein Interaction Property Similarity Analysis) is a procedure to compare and analyze protein molecular interaction fields, such as the electrostatic potential. PIPSA may assist in protein functional assignment, classification of proteins, the comparison of binding properties and the estimation of enzyme kinetic parameters. webPIPSA is a web server that enables the use of PIPSA to compare and analyze protein electrostatic potentials. While PIPSA can be run with downloadable software (see http://projects.eml.org/mcm/software/pipsa), webPIPSA extends and simplifies a PIPSA run. This allows non-expert users to perform PIPSA for their protein datasets. With input protein coordinates, the superposition of protein structures, as well as the computation and analysis of electrostatic potentials, is automated. The results are provided as electrostatic similarity matrices from an all-pairwise comparison of the proteins which can be subjected to clustering and visualized as epograms (tree-like diagrams showing electrostatic potential differences) or heat maps. webPIPSA is freely available at: http://pipsa.eml.org. PMID:18420653

The Effect of Desulfation of Chondroitin Sulfate on Interactions with Positively Charged Growth Factors and Upregulation of Cartilaginous Markers in Encapsulated MSCs

PubMed Central

Lim, Jeremy J.; Temenoff, Johnna S.

2013-01-01

Sulfated glycosaminoglycans (GAGs) are known to interact electrostatically with positively charged growth factors to modulate signaling. Therefore, regulating the degree of sulfation of GAGs may be a promising approach to tailor biomaterial carriers for controlled growth factor delivery and release. For this study, chondroitin sulfate (CS) was first desulfated to form chondroitin, and resulting crosslinked CS and chondroitin hydrogels were examined in vitro for release of positively charged model protein (histone) and for their effect on cartilaginous differentiation of encapsulated human mesenchymal stem cells (MSCs). Desulfation significantly increased the release of histone from chondroitin hydrogels (30.6±2.3 ìg released over 8 days, compared to natively sulfated CS with 20.2±0.8 ìg), suggesting that sulfation alone plays a significant role in modulating protein interactions with GAG hydrogels. MSCs in chondroitin hydrogels significantly upregulated gene expression of collagen II and aggrecan by day 21 in chondrogenic medium (115±100 and 23.1±7.9 fold upregulation of collagen II and aggrecan, respectively), compared to CS and PEG-based swelling controls, indicating that desulfation may actually enhance the response of MSCs to soluble chondrogenic cues, such as TGF-â1. Thus, desulfated chondroitin materials present a promising biomaterial tool to further investigate electrostatic GAG/growth factor interactions, especially for repair of cartilaginous tissues. PMID:23570717

Adsorption of guanidinium collectors on aluminosilicate minerals - a density functional study.

PubMed

Nulakani, Naga Venkateswara Rao; Baskar, Prathab; Patra, Abhay Shankar; Subramanian, Venkatesan

2015-10-07

In this density functional theory based investigation, we have modelled and studied the adsorption behaviour of guanidinium cations and substituted (phenyl, methoxy phenyl, nitro phenyl and di-nitro phenyl) guanidinium cationic collectors on the basal surfaces of kaolinite and goethite. The adsorption behaviour is assessed in three different media, such as gas, explicit water and pH medium, to understand the affinity of GC collectors to the SiO4 tetrahedral and AlO6 octahedral surfaces of kaolinite. The tetrahedral siloxane surface possesses a larger binding affinity to GC collectors than the octahedral sites due to the presence of surface exposed oxygen atoms that are active in the intermolecular interactions. Furthermore, the inductive electronic effects of substituted guanidinium cations also play a key role in the adsorption mechanism. Highly positive cations result in a stronger electrostatic interaction and preferential adsorption with the kaolinite surfaces than low positive cations. Computed interaction energies and electron densities at the bond critical points suggest that the adsorption of guanidinium cations on the surfaces of kaolinite and goethite is due to the formation of intra/inter hydrogen bonding networks. Also, the electrostatic interaction favours the high adsorption ability of GC collectors in the pH medium than gas phase and water medium. The structures and energies of GC collectors pave an intuitive view for future experimental studies on mineral flotation.

Particle transport through hydrogels is charge asymmetric.

PubMed

Zhang, Xiaolu; Hansing, Johann; Netz, Roland R; DeRouchey, Jason E

2015-02-03

Transport processes within biological polymer networks, including mucus and the extracellular matrix, play an important role in the human body, where they serve as a filter for the exchange of molecules and nanoparticles. Such polymer networks are complex and heterogeneous hydrogel environments that regulate diffusive processes through finely tuned particle-network interactions. In this work, we present experimental and theoretical studies to examine the role of electrostatics on the basic mechanisms governing the diffusion of charged probe molecules inside model polymer networks. Translational diffusion coefficients are determined by fluorescence correlation spectroscopy measurements for probe molecules in uncharged as well as cationic and anionic polymer solutions. We show that particle transport in the charged hydrogels is highly asymmetric, with diffusion slowed down much more by electrostatic attraction than by repulsion, and that the filtering capability of the gel is sensitive to the solution ionic strength. Brownian dynamics simulations of a simple model are used to examine key parameters, including interaction strength and interaction range within the model networks. Simulations, which are in quantitative agreement with our experiments, reveal the charge asymmetry to be due to the sticking of particles at the vertices of the oppositely charged polymer networks. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

On the Importance of Polar Interactions for Complexes Containing Intrinsically Disordered Proteins

PubMed Central

Wong, Eric T. C.; Na, Dokyun; Gsponer, Jörg

2013-01-01

There is a growing recognition for the importance of proteins with large intrinsically disordered (ID) segments in cell signaling and regulation. ID segments in these proteins often harbor regions that mediate molecular recognition. Coupled folding and binding of the recognition regions has been proposed to confer high specificity to interactions involving ID segments. However, researchers recently questioned the origin of the interaction specificity of ID proteins because of the overrepresentation of hydrophobic residues in their interaction interfaces. Here, we focused on the role of polar and charged residues in interactions mediated by ID segments. Making use of the extended nature of most ID segments when in complex with globular proteins, we first identified large numbers of complexes between globular proteins and ID segments by using radius-of-gyration-based selection criteria. Consistent with previous studies, we found the interfaces of these complexes to be enriched in hydrophobic residues, and that these residues contribute significantly to the stability of the interaction interface. However, our analyses also show that polar interactions play a larger role in these complexes than in structured protein complexes. Computational alanine scanning and salt-bridge analysis indicate that interfaces in ID complexes are highly complementary with respect to electrostatics, more so than interfaces of globular proteins. Follow-up calculations of the electrostatic contributions to the free energy of binding uncovered significantly stronger Coulombic interactions in complexes harbouring ID segments than in structured protein complexes. However, they are counter-balanced by even higher polar-desolvation penalties. We propose that polar interactions are a key contributing factor to the observed high specificity of ID segment-mediated interactions. PMID:23990768

Advances in visual representation of molecular potentials.

PubMed

Du, Qi-Shi; Huang, Ri-Bo; Chou, Kuo-Chen

2010-06-01

The recent advances in visual representations of molecular properties in 3D space are summarized, and their applications in molecular modeling study and rational drug design are introduced. The visual representation methods provide us with detailed insights into protein-ligand interactions, and hence can play a major role in elucidating the structure or reactivity of a biomolecular system. Three newly developed computation and visualization methods for studying the physical and chemical properties of molecules are introduced, including their electrostatic potential, lipophilicity potential and excess chemical potential. The newest application examples of visual representations in structure-based rational drug are presented. The 3D electrostatic potentials, calculated using the empirical method (EM-ESP), in which the classical Coulomb equation and traditional atomic partial changes are discarded, are highly consistent with the results by the higher level quantum chemical method. The 3D lipophilicity potentials, computed by the heuristic molecular lipophilicity potential method based on the principles of quantum mechanics and statistical mechanics, are more accurate and reliable than those by using the traditional empirical methods. The 3D excess chemical potentials, derived by the reference interaction site model-hypernetted chain theory, provide a new tool for computational chemistry and molecular modeling. For structure-based drug design, the visual representations of molecular properties will play a significant role in practical applications. It is anticipated that the new advances in computational chemistry will stimulate the development of molecular modeling methods, further enriching the visual representation techniques for rational drug design, as well as other relevant fields in life science.

Precise control of surface electrostatic forces on polymer brush layers with opposite charges for resistance to protein adsorption.

PubMed

Sakata, Sho; Inoue, Yuuki; Ishihara, Kazuhiko

2016-10-01

Various molecular interaction forces are generated during protein adsorption process on material surfaces. Thus, it is necessary to control them to suppress protein adsorption and the subsequent cell and tissue responses. A series of binary copolymer brush layers were prepared via surface-initiated atom transfer radical polymerization, by mixing the cationic monomer unit and anionic monomer unit randomly in various ratios. Surface characterization revealed that the constructed copolymer brush layers exhibited an uniform super-hydrophilic nature and different surface potentials. The strength of the electrostatic interaction forces operating on these mixed-charge copolymer brush surfaces was evaluated quantitatively using force-versus-distance (f-d) curve measurements by atomic force microscopy (AFM) and probes modified by negatively charged carboxyl groups or positively charged amino groups. The electrostatic interaction forces were determined based on the charge ratios of the copolymer brush layers. Notably, the surface containing equivalent cationic/anionic monomer units hardly interacted with both the charged groups. Furthermore, the protein adsorption force and the protein adsorption mass on these surfaces were examined by AFM f-d curve measurement and surface plasmon resonance measurement, respectively. To clarify the influence of the electrostatic interaction on the protein adsorption behavior on the surface, three kinds of proteins having negative, positive, and relatively neutral net charges under physiological conditions were used in this study. We quantitatively demonstrated that the amount of adsorbed proteins on the surfaces would have a strong correlation with the strength of surface-protein interaction forces, and that the strength of surface-protein interaction forces would be determined from the combination between the properties of the electrostatic interaction forces on the surfaces and the charge properties of the proteins. Especially, the copolymer brush surface composed of equivalent cationic/anionic monomer units exhibited no significant interaction forces, and dramatically suppressed the adsorption of proteins regardless of their charge properties. We conclude that the established methodology could elucidate relationship between the protein adsorption behavior and molecular interaction, especially the electrostatic interaction forces, and demonstrated that the suppression of the electrostatic interactions with the ionic functional groups would be important for the development of new polymeric biomaterials with a high repellency of protein adsorption. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular electrostatics for probing lone pair-π interactions.

PubMed

Mohan, Neetha; Suresh, Cherumuttathu H; Kumar, Anmol; Gadre, Shridhar R

2013-11-14

An electrostatics-based approach has been proposed for probing the weak interactions between lone pair containing molecules and π deficient molecular systems. For electron-rich molecules, the negative minima in molecular electrostatic potential (MESP) topography give the location of electron localization and the MESP value at the minimum (Vmin) quantifies the electron-rich character of that region. Interactive behavior of a lone pair bearing molecule with electron deficient π-systems, such as hexafluorobenzene, 1,3,5-trinitrobenzene, 2,4,6-trifluoro-1,3,5-triazine and 1,2,4,5-tetracyanobenzene explored within DFT brings out good correlation of the lone pair-π interaction energy (E(int)) with the Vmin value of the electron-rich system. Such interaction is found to be portrayed well with the Electrostatic Potential for Intermolecular Complexation (EPIC) model. On the basis of the precise location of MESP minimum, a prediction for the orientation of a lone pair bearing molecule with an electron deficient π-system is possible in the majority of the cases studied.

Interactions of the α-subunits of heterotrimeric G-proteins with GPCRs, effectors and RGS proteins: a critical review and analysis of interacting surfaces, conformational shifts, structural diversity and electrostatic potentials.

PubMed

Baltoumas, Fotis A; Theodoropoulou, Margarita C; Hamodrakas, Stavros J

2013-06-01

G-protein coupled receptors (GPCRs) are one of the largest families of membrane receptors in eukaryotes. Heterotrimeric G-proteins, composed of α, β and γ subunits, are important molecular switches in the mediation of GPCR signaling. Receptor stimulation after the binding of a suitable ligand leads to G-protein heterotrimer activation and dissociation into the Gα subunit and Gβγ heterodimer. These subunits then interact with a large number of effectors, leading to several cell responses. We studied the interactions between Gα subunits and their binding partners, using information from structural, mutagenesis and Bioinformatics studies, and conducted a series of comparisons of sequence, structure, electrostatic properties and intermolecular energies among different Gα families and subfamilies. We identified a number of Gα surfaces that may, in several occasions, participate in interactions with receptors as well as effectors. The study of Gα interacting surfaces in terms of sequence, structure and electrostatic potential reveals features that may account for the Gα subunit's behavior towards its interacting partners. The electrostatic properties of the Gα subunits, which in some cases differ greatly not only between families but also between subfamilies, as well as the G-protein interacting surfaces of effectors and regulators of G-protein signaling (RGS) suggest that electrostatic complementarity may be an important factor in G-protein interactions. Energy calculations also support this notion. This information may be useful in future studies of G-protein interactions with GPCRs and effectors. Copyright © 2013 Elsevier Inc. All rights reserved.

Interaction-component analysis of the hydration and urea effects on cytochrome c

NASA Astrophysics Data System (ADS)

Yamamori, Yu; Ishizuka, Ryosuke; Karino, Yasuhito; Sakuraba, Shun; Matubayasi, Nobuyuki

2016-02-01

Energetics was analyzed for cytochrome c in pure-water solvent and in a urea-water mixed solvent to elucidate the solvation effect in the structural variation of the protein. The solvation free energy was computed through all-atom molecular dynamics simulation combined with the solution theory in the energy representation, and its correlations were examined over sets of protein structures against the electrostatic and van der Waals components in the average interaction energy of the protein with the solvent and the excluded-volume component in the solvation free energy. It was observed in pure-water solvent that the solvation free energy varies in parallel to the electrostatic component with minor roles played by the van der Waals and excluded-volume components. The effect of urea on protein structure was then investigated in terms of the free-energy change upon transfer of the protein solute from pure-water solvent to the urea-water mixed solvent. The decomposition of the transfer free energy into the contributions from urea and water showed that the urea contribution is partially canceled by the water contribution and governs the total free energy of transfer. When correlated against the change in the solute-solvent interaction energy upon transfer and the corresponding changes in the electrostatic, van der Waals, and excluded-volume components, the transfer free energy exhibited strong correlations with the total change in the solute-solvent energy and its van der Waals component. The solute-solvent energy was decomposed into the contributions from the protein backbone and side chain, furthermore, and neither of the contributions was seen to be decisive in the correlation to the transfer free energy.

Electrostatic Steering Accelerates C3d:CR2 Association.

PubMed

Mohan, Rohith R; Huber, Gary A; Morikis, Dimitrios

2016-08-25

Electrostatic effects are ubiquitous in protein interactions and are found to be pervasive in the complement system as well. The interaction between complement fragment C3d and complement receptor 2 (CR2) has evolved to become a link between innate and adaptive immunity. Electrostatic interactions have been suggested to be the driving factor for the association of the C3d:CR2 complex. In this study, we investigate the effects of ionic strength and mutagenesis on the association of C3d:CR2 through Brownian dynamics simulations. We demonstrate that the formation of the C3d:CR2 complex is ionic strength-dependent, suggesting the presence of long-range electrostatic steering that accelerates the complex formation. Electrostatic steering occurs through the interaction of an acidic surface patch in C3d and the positively charged CR2 and is supported by the effects of mutations within the acidic patch of C3d that slow or diminish association. Our data are in agreement with previous experimental mutagenesis and binding studies and computational studies. Although the C3d acidic patch may be locally destabilizing because of unfavorable Coulombic interactions of like charges, it contributes to the acceleration of association. Therefore, acceleration of function through electrostatic steering takes precedence to stability. The site of interaction between C3d and CR2 has been the target for delivery of CR2-bound nanoparticle, antibody, and small molecule biomarkers, as well as potential therapeutics. A detailed knowledge of the physicochemical basis of C3d:CR2 association may be necessary to accelerate biomarker and drug discovery efforts.

DEPPDB - DNA electrostatic potential properties database. Electrostatic properties of genome DNA elements.

PubMed

Osypov, Alexander A; Krutinin, Gleb G; Krutinina, Eugenia A; Kamzolova, Svetlana G

2012-04-01

Electrostatic properties of genome DNA are important to its interactions with different proteins, in particular, related to transcription. DEPPDB - DNA Electrostatic Potential (and other Physical) Properties Database - provides information on the electrostatic and other physical properties of genome DNA combined with its sequence and annotation of biological and structural properties of genomes and their elements. Genomes are organized on taxonomical basis, supporting comparative and evolutionary studies. Currently, DEPPDB contains all completely sequenced bacterial, viral, mitochondrial, and plastids genomes according to the NCBI RefSeq, and some model eukaryotic genomes. Data for promoters, regulation sites, binding proteins, etc., are incorporated from established DBs and literature. The database is complemented by analytical tools. User sequences calculations are available. Case studies discovered electrostatics complementing DNA bending in E.coli plasmid BNT2 promoter functioning, possibly affecting host-environment metabolic switch. Transcription factors binding sites gravitate to high potential regions, confirming the electrostatics universal importance in protein-DNA interactions beyond the classical promoter-RNA polymerase recognition and regulation. Other genome elements, such as terminators, also show electrostatic peculiarities. Most intriguing are gene starts, exhibiting taxonomic correlations. The necessity of the genome electrostatic properties studies is discussed.

Deppdb--DNA electrostatic potential properties database: electrostatic properties of genome DNA.

PubMed

Osypov, Alexander A; Krutinin, Gleb G; Kamzolova, Svetlana G

2010-06-01

The electrostatic properties of genome DNA influence its interactions with different proteins, in particular, the regulation of transcription by RNA-polymerases. DEPPDB--DNA Electrostatic Potential Properties Database--was developed to hold and provide all available information on the electrostatic properties of genome DNA combined with its sequence and annotation of biological and structural properties of genome elements and whole genomes. Genomes in DEPPDB are organized on a taxonomical basis. Currently, the database contains all the completely sequenced bacterial and viral genomes according to NCBI RefSeq. General properties of the genome DNA electrostatic potential profile and principles of its formation are revealed. This potential correlates with the GC content but does not correspond to it exactly and strongly depends on both the sequence arrangement and its context (flanking regions). Analysis of the promoter regions for bacterial and viral RNA polymerases revealed a correspondence between the scale of these proteins' physical properties and electrostatic profile patterns. We also discovered a direct correlation between the potential value and the binding frequency of RNA polymerase to DNA, supporting the idea of the role of electrostatics in these interactions. This matches a pronounced tendency of the promoter regions to possess higher values of the electrostatic potential.

Electrostatic forces govern the binding mechanism of intrinsically disordered histone chaperones

PubMed Central

Liu, Chuanbo; Wang, Tianshu; Bai, Yawen; Wang, Jin

2017-01-01

A unified picture to understand the protein recognition and function must include the native binding complex structure ensembles and the underlying binding mechanisms involved in specific biological processes. However, quantifications of both binding complex structures and dynamical mechanisms are still challenging for IDP. In this study, we have investigated the underlying molecular mechanism of the chaperone Chz1 and histone H2A.Z-H2B association by equilibrium and kinetic stopped-flow fluorescence spectroscopy. The dependence of free energy and kinetic rate constant on electrolyte mean activity coefficient and urea concentration are uncovered. Our results indicate a previous unseen binding kinetic intermediate. An initial conformation selection step of Chz1 is also revealed before the formation of this intermediate state. Based on these observations, a mixed mechanism of three steps including both conformation selection and induced fit is proposed. By combination of the ion- and denaturant-induced experiments, we demonstrate that electrostatic forces play a dominant role in the recognition of bipolar charged intrinsically disordered protein Chz1 to its preferred partner H2A.Z-H2B. Both the intra-chain and inter-chain electrostatic interactions have direct impacts on the native collapsed structure and binding mechanism. PMID:28552960

A Comprehensive Docking and MM/GBSA Rescoring Study of Ligand Recognition upon Binding Antithrombin

DOE PAGES

Zhang, Xiaohua; Perez-Sanchez, Horacio; C. Lightstone, Felice

2017-04-06

A high-throughput virtual screening pipeline has been extended from single energetically minimized structure Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring to ensemble-average MM/GBSA rescoring. The correlation coefficient (R2) of calculated and experimental binding free energies for a series of antithrombin ligands has been improved from 0.36 to 0.69 when switching from the single-structure MM/GBSA rescoring to ensemble-average one. The electrostatic interactions in both solute and solvent are identified to play an important role in determining the binding free energy after the decomposition of the calculated binding free energy. Furthermore, the increasing negative charge of the compounds provides a more favorablemore » electrostatic energy change but creates a higher penalty for the solvation free energy. Such a penalty is compensated by the electrostatic energy change, which results in a better binding affinity. A highly hydrophobic ligand is determined by the docking program to be a non-specific binder. Finally, these results have demonstrated that it is very important to keep a few top poses for rescoring, if the binding is non-specific or the binding mode is not well determined by the docking calculation.« less

A Comprehensive Docking and MM/GBSA Rescoring Study of Ligand Recognition upon Binding Antithrombin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xiaohua; Perez-Sanchez, Horacio; C. Lightstone, Felice

A high-throughput virtual screening pipeline has been extended from single energetically minimized structure Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring to ensemble-average MM/GBSA rescoring. The correlation coefficient (R2) of calculated and experimental binding free energies for a series of antithrombin ligands has been improved from 0.36 to 0.69 when switching from the single-structure MM/GBSA rescoring to ensemble-average one. The electrostatic interactions in both solute and solvent are identified to play an important role in determining the binding free energy after the decomposition of the calculated binding free energy. Furthermore, the increasing negative charge of the compounds provides a more favorablemore » electrostatic energy change but creates a higher penalty for the solvation free energy. Such a penalty is compensated by the electrostatic energy change, which results in a better binding affinity. A highly hydrophobic ligand is determined by the docking program to be a non-specific binder. Finally, these results have demonstrated that it is very important to keep a few top poses for rescoring, if the binding is non-specific or the binding mode is not well determined by the docking calculation.« less

Diminish electrostatic in piezoresponse force microscopy through longer or ultra-stiff tips

NASA Astrophysics Data System (ADS)

Gomez, A.; Puig, T.; Obradors, X.

2018-05-01

Piezoresponse Force Microscopy is a powerful but delicate nanoscale technique that measures the electromechanical response resulting from the application of a highly localized electric field. Though mechanical response is normally due to piezoelectricity, other physical phenomena, especially electrostatic interaction, can contribute to the signal read. We address this problematic through the use of longer ultra-stiff probes providing state of the art sensitivity, with the lowest electrostatic interaction and avoiding working in high frequency regime. In order to find this solution we develop a theoretical description addressing the effects of electrostatic contributions in the total cantilever vibration and its quantification for different setups. The theory is subsequently tested in a Periodically Poled Lithium Niobate (PPLN) crystal, a sample with well-defined 0° and 180° domains, using different commercial available conductive tips. We employ the theoretical description to compare the electrostatic contribution effects into the total phase recorded. Through experimental data our description is corroborated for each of the tested commercially available probes. We propose that a larger probe length can be a solution to avoid electrostatic forces, so the cantilever-sample electrostatic interaction is reduced. Our proposed solution has great implications into avoiding artifacts while studying soft biological samples, multiferroic oxides, and thin film ferroelectric materials.

New strategy for protein interactions and application to structure-based drug design

NASA Astrophysics Data System (ADS)

Zou, Xiaoqin

One of the greatest challenges in computational biophysics is to predict interactions between biological molecules, which play critical roles in biological processes and rational design of therapeutic drugs. Biomolecular interactions involve delicate interplay between multiple interactions, including electrostatic interactions, van der Waals interactions, solvent effect, and conformational entropic effect. Accurate determination of these complex and subtle interactions is challenging. Moreover, a biological molecule such as a protein usually consists of thousands of atoms, and thus occupies a huge conformational space. The large degrees of freedom pose further challenges for accurate prediction of biomolecular interactions. Here, I will present our development of physics-based theory and computational modeling on protein interactions with other molecules. The major strategy is to extract microscopic energetics from the information embedded in the experimentally-determined structures of protein complexes. I will also present applications of the methods to structure-based therapeutic design. Supported by NSF CAREER Award DBI-0953839, NIH R01GM109980, and the American Heart Association (Midwest Affiliate) [13GRNT16990076].

Dendrimer-protein interactions versus dendrimer-based nanomedicine.

PubMed

Shcharbin, Dzmitry; Shcharbina, Natallia; Dzmitruk, Volha; Pedziwiatr-Werbicka, Elzbieta; Ionov, Maksim; Mignani, Serge; de la Mata, F Javier; Gómez, Rafael; Muñoz-Fernández, Maria Angeles; Majoral, Jean-Pierre; Bryszewska, Maria

2017-04-01

Dendrimers are hyperbranched polymers belonging to the huge class of nanomedical devices. Their wide application in biology and medicine requires understanding of the fundamental mechanisms of their interactions with biological systems. Summarizing, electrostatic force plays the predominant role in dendrimer-protein interactions, especially with charged dendrimers. Other kinds of interactions have been proven, such as H-bonding, van der Waals forces, and even hydrophobic interactions. These interactions depend on the characteristics of both participants: flexibility and surface charge of a dendrimer, rigidity of protein structure and the localization of charged amino acids at its surface. pH and ionic strength of solutions can significantly modulate interactions. Ligands and cofactors attached to a protein can also change dendrimer-protein interactions. Binding of dendrimers to a protein can change its secondary structure, conformation, intramolecular mobility and functional activity. However, this strongly depends on rigidity versus flexibility of a protein's structure. In addition, the potential applications of dendrimers to nanomedicine are reviwed related to dendrimer-protein interactions. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigation on the interaction between an antimicrobial in aquaculture, malachite green and hemocyanin from Mud Crab Scylla paramamosain

NASA Astrophysics Data System (ADS)

Li, Zhenxing; Tang, Boping; Zhang, Hongmei

2015-01-01

Interaction between malachite green and hemocyanin of crab plays a crucial role in the metabolism, distribution, and efficacy of toxic dyes in aquaculture. The mechanism of interaction between malachite green and Hc from mud crab was studied by using multi-spectral methods and molecular modeling in this work. The spectroscopic and thermodynamic data show that the interaction is a spontaneous process with the estimated enthalpy and entropy changes of -14.85(±1.86) kJ mol-1 and 30.38(±5.21) J mol-1 K-1, respectively. The binding sites of malachite green in hemocyanin mainly locate in the interface of protein. The hydrophobic and electrostatic forces are the primary contributors to the interaction between hemocyanin and malachite green. The results of ultraviolet-vis absorbance, circular dichroism, and synchronous fluorescence spectroscopy suggest that the binding of malachite green to hemocyanin induces some conformational changes of protein.

Electrostatic rate enhancement and transient complex of protein-protein association.

PubMed

Alsallaq, Ramzi; Zhou, Huan-Xiang

2008-04-01

The association of two proteins is bounded by the rate at which they, via diffusion, find each other while in appropriate relative orientations. Orientational constraints restrict this rate to approximately 10(5)-10(6) M(-1) s(-1). Proteins with higher association rates generally have complementary electrostatic surfaces; proteins with lower association rates generally are slowed down by conformational changes upon complex formation. Previous studies (Zhou, Biophys J 1997;73:2441-2445) have shown that electrostatic enhancement of the diffusion-limited association rate can be accurately modeled by $k_{\\bf D}$ = $k_{D}0\\ {exp} ( - \\langle U_{el} \\rangle;{\\star}/k_{B} T),$ where k(D) and k(D0) are the rates in the presence and absence of electrostatic interactions, respectively, U(el) is the average electrostatic interaction energy in a "transient-complex" ensemble, and k(B)T is the thermal energy. The transient-complex ensemble separates the bound state from the unbound state. Predictions of the transient-complex theory on four protein complexes were found to agree well with the experiment when the electrostatic interaction energy was calculated with the linearized Poisson-Boltzmann (PB) equation (Alsallaq and Zhou, Structure 2007;15:215-224). Here we show that the agreement is further improved when the nonlinear PB equation is used. These predictions are obtained with the dielectric boundary defined as the protein van der Waals surface. When the dielectric boundary is instead specified as the molecular surface, electrostatic interactions in the transient complex become repulsive and are thus predicted to retard association. Together these results demonstrate that the transient-complex theory is predictive of electrostatic rate enhancement and can help parameterize PB calculations. (c) 2007 Wiley-Liss, Inc.

On the interaction mechanisms of a p53 peptide and nutlin with the MDM2 and MDMX proteins: a Brownian dynamics study.

PubMed

ElSawy, Karim M; Verma, Chandra S; Joseph, Thomas L; Lane, David P; Twarock, Reidun; Caves, Leo S D

2013-02-01

The interaction of p53 with its regulators MDM2 and MDMX plays a major role in regulating the cell cycle. Inhibition of this interaction has become an important therapeutic strategy in oncology. Although MDM2 and MDMX share a very high degree of sequence/structural similarity, the small-molecule inhibitor nutlin appears to be an efficient inhibitor only of the p53-MDM2 interaction. Here, we investigate the mechanism of interaction of nutlin with these two proteins and contrast it with that of p53 using Brownian dynamics simulations. In contrast to earlier attempts to examine the bound states of the partners, here we locate initial reaction events in these interactions by identifying the regions of space around MDM2/MDMX, where p53/nutlin experience associative encounters with prolonged residence times relative to that in bulk solution. We find that the initial interaction of p53 with MDM2 is long-lived relative to nutlin, but, unlike nutlin, it takes place at the N- and C termini of the MDM2 protein, away from the binding site, suggestive of an allosteric mechanism of action. In contrast, nutlin initially interacts with MDM2 directly at the clefts of the binding site. The interaction of nutlin with MDMX, however, is very short-lived compared with MDM2 and does not show such direct initial interactions with the binding site. Comparison of the topology of the electrostatic potentials of MDM2 and MDMX and the locations of the initial encounters with p53/nutlin in tandem with structure-based sequence alignment revealed that the origin of the diminished activity of nutlin toward MDMX relative to MDM2 may stem partly from the differing topologies of the electrostatic potentials of the two proteins. Glu25 and Lys51 residues underpin these topological differences and appear to collectively play a key role in channelling nutlin directly toward the binding site on the MDM2 surface and are absent in MDMX. The results, therefore, provide new insight into the mechanism of p53/nutlin interactions with MDM2 and MDMX and could potentially have a broader impact on anticancer drug optimization strategies.

Study on the interaction between cinnamic acid and lysozyme

NASA Astrophysics Data System (ADS)

Zhang, Hong-Mei; Chen, Jian; Zhou, Qiu-Hua; Shi, Yue-Qin; Wang, Yan-Qing

2011-02-01

The interaction between lysozyme and cinnamic acid was investigated systematically by ultraviolet-vis absorbance, circular dichroism, fluorescence, synchronous fluorescence, and three-dimensional fluorescence spectra techniques at pH 7.40. The binding constants, quenching mechanism, and the number of binding sites were determined by the quenching of lysozyme fluorescence in presence of cinnamic acid. The results showed that the fluorescence quenching of lysozyme by cinnamic acid was a result of the formation of cinnamic acid-lysozyme complex. The hydrophobic and electrostatic interactions played major roles in stabilizing the complex; the distance r between donor and acceptor was obtained to be 2.07 nm according to Förster's theory; the effect of cinnamic acid on the conformation of lysozyme was analyzed using synchronous fluorescence, circular dichroism and three-dimensional fluorescence spectra.

Role of Electrostatics in Protein-RNA Binding: The Global vs the Local Energy Landscape.

PubMed

Ghaemi, Zhaleh; Guzman, Irisbel; Gnutt, David; Luthey-Schulten, Zaida; Gruebele, Martin

2017-09-14

U1A protein-stem loop 2 RNA association is a basic step in the assembly of the spliceosomal U1 small nuclear ribonucleoprotein. Long-range electrostatic interactions due to the positive charge of U1A are thought to provide high binding affinity for the negatively charged RNA. Short range interactions, such as hydrogen bonds and contacts between RNA bases and protein side chains, favor a specific binding site. Here, we propose that electrostatic interactions are as important as local contacts in biasing the protein-RNA energy landscape toward a specific binding site. We show by using molecular dynamics simulations that deletion of two long-range electrostatic interactions (K22Q and K50Q) leads to mutant-specific alternative RNA bound states. One of these states preserves short-range interactions with aromatic residues in the original binding site, while the other one does not. We test the computational prediction with experimental temperature-jump kinetics using a tryptophan probe in the U1A-RNA binding site. The two mutants show the distinct predicted kinetic behaviors. Thus, the stem loop 2 RNA has multiple binding sites on a rough RNA-protein binding landscape. We speculate that the rough protein-RNA binding landscape, when biased to different local minima by electrostatics, could be one way that protein-RNA interactions evolve toward new binding sites and novel function.

Electrostatic Interactions Between Glycosaminoglycan Molecules

NASA Astrophysics Data System (ADS)

Song, Fan; Moyne, Christian; Bai, Yi-Long

2005-02-01

The electrostatic interactions between nearest-neighbouring chondroitin sulfate glycosaminoglycan (CS-GAG) molecular chains are obtained on the bottle brush conformation of proteoglycan aggrecan based on an asymptotic solution of the Poisson-Boltzmann equation the CS-GAGs satisfy under the physiological conditions of articular cartilage. The present results show that the interactions are associated intimately with the minimum separation distance and mutual angle between the molecular chains themselves. Further analysis indicates that the electrostatic interactions are not only expressed to be purely exponential in separation distance and decrease with the increasing mutual angle but also dependent sensitively on the saline concentration in the electrolyte solution within the tissue, which is in agreement with the existed relevant conclusions.

Internal force field in proteins seen by divergence entropy

PubMed Central

Marchewka, Damian; Banach, Mateusz; Roterman, Irena

2011-01-01

The characteristic distribution of non-binding interactions in a protein is described. It establishes that hydrophobic interactions can be characterized by suitable 3D Gauss functions while electrostatic interactions generally follow a random distribution. The implementation of this observation suggests differentiated optimization procedure for these two types of interactions. The electrostatic interaction may follow traditional energy optimization while the criteria for convergence shall measure the accordance with 3-D Gauss function. PMID:21769190

The polarized Debye sheath effect on Kadomtsev-Petviashvili electrostatic structures in strongly coupled dusty plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shahmansouri, M.; Alinejad, H.

2015-04-15

We give a theoretical investigation on the dynamics of nonlinear electrostatic waves in a strongly coupled dusty plasma with strong electrostatic interaction between dust grains in the presence of the polarization force (i.e., the force due to the polarized Debye sheath). Adopting a reductive perturbation method, we derived a three-dimensional Kadomtsev-Petviashvili equation that describes the evolution of weakly nonlinear electrostatic localized waves. The energy integral equation is used to study the existence domains of the localized structures. The analysis provides the localized structure existence region, in terms of the effects of strong interaction between the dust particles and polarization force.

The role of charged surface residues in the binding ability of small hubs in protein-protein interaction networks

PubMed Central

Patil, Ashwini; Nakamura, Haruki

2007-01-01

Hubs are highly connected proteins in a protein-protein interaction network. Previous work has implicated disordered domains and high surface charge as the properties significant in the ability of hubs to bind multiple proteins. While conformational flexibility of disordered domains plays an important role in the binding ability of large hubs, high surface charge is the dominant property in small hubs. In this study, we further investigate the role of the high surface charge in the binding ability of small hubs in the absence of disordered domains. Using multipole expansion, we find that the charges are highly distributed over the hub surfaces. Residue enrichment studies show that the charged residues in hubs are more prevalent on the exposed surface, with the exception of Arg, which is predominantly found at the interface, as compared to non-hubs. This suggests that the charged residues act primarily from the exposed surface rather than the interface to affect the binding ability of small hubs. They do this through (i) enhanced intra-molecular electrostatic interactions to lower the desolvation penalty, (ii) indirect long – range intermolecular interactions with charged residues on the partner proteins for better complementarity and electrostatic steering, and (iii) increased solubility for enhanced diffusion-controlled rate of binding. Along with Arg, we also find a high prevalence of polar residues Tyr, Gln and His and the hydrophobic residue Met at the interfaces of hubs, all of which have the ability to form multiple types of interactions, indicating that the interfaces of hubs are optimized to participate in multiple interactions. PMID:27857564

Micro-mechanics of electrostatically stabilized suspensions of cellulose nanofibrils under steady state shear flow.

PubMed

Martoïa, F; Dumont, P J J; Orgéas, L; Belgacem, M N; Putaux, J-L

2016-02-14

In this study, we characterized and modeled the rheology of TEMPO-oxidized cellulose nanofibril (NFC) aqueous suspensions with electrostatically stabilized and unflocculated nanofibrous structures. These colloidal suspensions of slender and wavy nanofibers exhibited a yield stress and a shear thinning behavior at low and high shear rates, respectively. Both the shear yield stress and the consistency of these suspensions were power-law functions of the NFC volume fraction. We developed an original multiscale model for the prediction of the rheology of these suspensions. At the nanoscale, the suspensions were described as concentrated systems where NFCs interacted with the Newtonian suspending fluid through Brownian motion and long range fluid-NFC hydrodynamic interactions, as well as with each other through short range hydrodynamic and repulsive colloidal interaction forces. These forces were estimated using both the experimental results and 3D networks of NFCs that were numerically generated to mimic the nanostructures of NFC suspensions under shear flow. They were in good agreement with theoretical and measured forces for model colloidal systems. The model showed the primary role played by short range hydrodynamic and colloidal interactions on the rheology of NFC suspensions. At low shear rates, the origin of the yield stress of NFC suspensions was attributed to the combined contribution of repulsive colloidal interactions and the topology of the entangled NFC networks in the suspensions. At high shear rates, both concurrent colloidal and short (in some cases long) range hydrodynamic interactions could be at the origin of the shear thinning behavior of NFC suspensions.

The role of charged surface residues in the binding ability of small hubs in protein-protein interaction networks.

PubMed

Patil, Ashwini; Nakamura, Haruki

2007-01-01

Hubs are highly connected proteins in a protein-protein interaction network. Previous work has implicated disordered domains and high surface charge as the properties significant in the ability of hubs to bind multiple proteins. While conformational flexibility of disordered domains plays an important role in the binding ability of large hubs, high surface charge is the dominant property in small hubs. In this study, we further investigate the role of the high surface charge in the binding ability of small hubs in the absence of disordered domains. Using multipole expansion, we find that the charges are highly distributed over the hub surfaces. Residue enrichment studies show that the charged residues in hubs are more prevalent on the exposed surface, with the exception of Arg, which is predominantly found at the interface, as compared to non-hubs. This suggests that the charged residues act primarily from the exposed surface rather than the interface to affect the binding ability of small hubs. They do this through (i) enhanced intra-molecular electrostatic interactions to lower the desolvation penalty, (ii) indirect long - range intermolecular interactions with charged residues on the partner proteins for better complementarity and electrostatic steering, and (iii) increased solubility for enhanced diffusion-controlled rate of binding. Along with Arg, we also find a high prevalence of polar residues Tyr, Gln and His and the hydrophobic residue Met at the interfaces of hubs, all of which have the ability to form multiple types of interactions, indicating that the interfaces of hubs are optimized to participate in multiple interactions.

Unveiling the Mode of Interaction of Berberine Alkaloid in Different Supramolecular Confined Environments: Interplay of Surface Charge between Nano-Confined Charged Layer and DNA.

PubMed

Kundu, Niloy; Roy, Arpita; Banik, Debasis; Sarkar, Nilmoni

2016-02-18

In this Article, we demonstrate a detailed characterization of binding interaction of berberine chloride (BBCl) with calf-thymus DNA (CT-DNA) in buffer solution as well as in two differently charged reverse micelles (RMs). The photophyscial properties of this alkaloid have been modulated within these microheterogeneous bioassemblies. The mode of binding of this alkaloid with DNA is of debate to date. However, fluorescence spectroscopic measurements, circular dichroism (CD) measurement, and temperature-dependent study unambiguously establish that BBCl partially intercalates into the DNA base pairs. The nonplanarity imposed by partial saturation in their structure causes the nonclassical types of intercalation into DNA. Besides the intercalation, electrostatic interactions also play a significant role in the binding between BBCl and DNA. DNA structure turns into a condensed form after encapsulation into RMs, which is followed by the CD spectra and microscopy study. The probe location and dynamics in the nanopool of the RMs depended on the electrostatic interaction between the charged surfactants and cationic berberine. The structural alteration of CT-DNA from B form to condensed form and the interplay of surface charge between RMs and DNA determine the interaction between the alkaloid and DNA in RMs. Time-resolved study and fluorescence anisotropy measurements successfully provide the binding interaction of BBCl in the nanopool of the RMs in the absence and in the presence of DNA. This study motivates us to judge further the potential applicability of this alkaloid in other biological systems or other biomimicking organized assemblies.

Accurate potentiometric determination of lipid membrane-water partition coefficients and apparent dissociation constants of ionizable drugs: electrostatic corrections.

PubMed

Elsayed, Mustafa M A; Vierl, Ulrich; Cevc, Gregor

2009-06-01

Potentiometric lipid membrane-water partition coefficient studies neglect electrostatic interactions to date; this leads to incorrect results. We herein show how to account properly for such interactions in potentiometric data analysis. We conducted potentiometric titration experiments to determine lipid membrane-water partition coefficients of four illustrative drugs, bupivacaine, diclofenac, ketoprofen and terbinafine. We then analyzed the results conventionally and with an improved analytical approach that considers Coulombic electrostatic interactions. The new analytical approach delivers robust partition coefficient values. In contrast, the conventional data analysis yields apparent partition coefficients of the ionized drug forms that depend on experimental conditions (mainly the lipid-drug ratio and the bulk ionic strength). This is due to changing electrostatic effects originating either from bound drug and/or lipid charges. A membrane comprising 10 mol-% mono-charged molecules in a 150 mM (monovalent) electrolyte solution yields results that differ by a factor of 4 from uncharged membranes results. Allowance for the Coulombic electrostatic interactions is a prerequisite for accurate and reliable determination of lipid membrane-water partition coefficients of ionizable drugs from potentiometric titration data. The same conclusion applies to all analytical methods involving drug binding to a surface.

Effect of electrostatic interactions on the ultrafiltration behavior of charged bacterial capsular polysaccharides.

PubMed

Hadidi, Mahsa; Buckley, John J; Zydney, Andrew L

2016-11-01

Charged polysaccharides are used in the food industry, as cosmetics, and as vaccines. The viscosity, thermodynamics, and hydrodynamic properties of these charged polysaccharides are known to be strongly dependent on the solution ionic strength because of both inter- and intramolecular electrostatic interactions. The goal of this work was to quantitatively describe the effect of these electrostatic interactions on the ultrafiltration behavior of several charged capsular polysaccharides obtained from Streptococcus pneumoniae and used in the production of Pneumococcus vaccines. Ultrafiltration data were obtained using various Biomax™ polyethersulfone membranes with different nominal molecular weight cutoffs. Polysaccharide transmission decreased with decreasing ionic strength primarily because of the expansion of the charged polysaccharide associated with intramolecular electrostatic repulsion. Data were in good agreement with a simple theoretical model based on solute partitioning in porous membranes, with the effective size of the different polysaccharide serotypes evaluated using size exclusion chromatography at the same ionic conditions. These results provide fundamental insights and practical guidelines for exploiting the effects of electrostatic interactions during the ultrafiltration of charged polysaccharides. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1531-1538, 2016. © 2016 American Institute of Chemical Engineers.

Electrostatically confined nanoparticle interactions and dynamics.

PubMed

Eichmann, Shannon L; Anekal, Samartha G; Bevan, Michael A

2008-02-05

We report integrated evanescent wave and video microscopy measurements of three-dimensional trajectories of 50, 100, and 250 nm gold nanoparticles electrostatically confined between parallel planar glass surfaces separated by 350 and 600 nm silica colloid spacers. Equilibrium analyses of single and ensemble particle height distributions normal to the confining walls produce net electrostatic potentials in excellent agreement with theoretical predictions. Dynamic analyses indicate lateral particle diffusion coefficients approximately 30-50% smaller than expected from predictions including the effects of the equilibrium particle distribution within the gap and multibody hydrodynamic interactions with the confining walls. Consistent analyses of equilibrium and dynamic information in each measurement do not indicate any roles for particle heating or hydrodynamic slip at the particle or wall surfaces, which would both increase diffusivities. Instead, lower than expected diffusivities are speculated to arise from electroviscous effects enhanced by the relative extent (kappaa approximately 1-3) and overlap (kappah approximately 2-4) of electrostatic double layers on the particle and wall surfaces. These results demonstrate direct, quantitative measurements and a consistent interpretation of metal nanoparticle electrostatic interactions and dynamics in a confined geometry, which provides a basis for future similar measurements involving other colloidal forces and specific biomolecular interactions.

Role of Subunit Exchange and Electrostatic Interactions on the Chaperone Activity of Mycobacterium leprae HSP18

PubMed Central

Nandi, Sandip Kumar; Panda, Alok Kumar; Chakraborty, Ayon; Ray, Sougata Sinha; Biswas, Ashis

2015-01-01

Mycobacterium leprae HSP18, a major immunodominant antigen of M. leprae pathogen, is a small heat shock protein. Previously, we reported that HSP18 is a molecular chaperone that prevents aggregation of different chemically and thermally stressed client proteins and assists refolding of denatured enzyme at normal temperature. We also demonstrated that it can efficiently prevent the thermal killing of E. coli at higher temperature. However, molecular mechanism behind the chaperone function of HSP18 is still unclear. Therefore, we studied the structure and chaperone function of HSP18 at normal temperature (25°C) as well as at higher temperatures (31–43°C). Our study revealed that the chaperone function of HSP18 is enhanced significantly with increasing temperature. Far- and near-UV CD experiments suggested that its secondary and tertiary structure remain intact in this temperature range (25–43°C). Besides, temperature has no effect on the static oligomeric size of this protein. Subunit exchange study demonstrated that subunits of HSP18 exchange at 25°C with a rate constant of 0.018 min-1. Both rate of subunit exchange and chaperone activity of HSP18 is found to increase with rise in temperature. However, the surface hydrophobicity of HSP18 decreases markedly upon heating and has no correlation with its chaperone function in this temperature range. Furthermore, we observed that HSP18 exhibits diminished chaperone function in the presence of NaCl at 25°C. At elevated temperatures, weakening of interactions between HSP18 and stressed client proteins in the presence of NaCl results in greater reduction of its chaperone function. The oligomeric size, rate of subunit exchange and structural stability of HSP18 were also found to decrease when electrostatic interactions were weakened. These results clearly indicated that subunit exchange and electrostatic interactions play a major role in the chaperone function of HSP18. PMID:26098662

Mechanism of the dielectric enhancement in polymer-alumina nano-particle composites

NASA Astrophysics Data System (ADS)

Jacob, Rebecca; Jacob, Anne Pavitra; Mainwaring, David E.

2009-09-01

Polymer-alumina nano-composites with enhanced dielectric properties as a possibility to enable the miniaturization of devices have been reported. The enhancement of dielectric properties was found to be unique to the polymer. In the present work, the mechanism of the dielectric enhancement is established by performing ab initio molecular orbital calculations in order to study the molecular interactions in the interfacial region between the alumina-nano-particle surface and the polymer medium. The calculations predict the existence of strong electrostatic attraction between the positive charge on the aluminium of the alumina clusters and the negative charge of the oxygens of the polymer at the polymer-nano-particle interface resulting in an increase in the dipole moment and the polarization of the system leading to enhanced dielectric properties. The oxygen thus plays a dual role by involving in covalent bonding with the polymer chain and electrostatic bonding interactions with the alumina nano-particles. The unique structure of the polymer provides the highly electronegative oxygens, as carbonyl groups or ether linkages in conjugation with aromatic rings in an extended polymer chain system, facilitating this type of bonding at the interface.

Pre-combustion CO2 capture by transition metal ions embedded in phthalocyanine sheets

NASA Astrophysics Data System (ADS)

Lü, Kun; Zhou, Jian; Zhou, Le; Chen, X. S.; Chan, Siew Hwa; Sun, Qiang

2012-06-01

Transition metal (TM) embedded two-dimensional phthalocyanine (Pc) sheets have been recently synthesized in experiments [M. Abel, S. Clair, O. Ourdjini, M. Mossoyan, and L. Porte, J. Am. Chem. Soc. 133, 1203 (2010)], 10.1021/ja108628r, where the transition metal ions are uniformly distributed in porous structures, providing the possibility of capturing gas molecules. Using first principles and grand canonical Monte Carlo simulations, TMPc sheets (TM = Sc, Ti, and Fe) are studied for pre-combustion CO2 capture by considering the adsorptions of H2/CO2 gas mixtures. It is found that ScPc sheet shows a good selectivity for CO2, and the excess uptake capacity of single-component CO2 on ScPc sheet at 298 K and 50 bar is found to be 2949 mg/g, larger than that of any other reported porous materials. Furthermore, electrostatic potential and natural bond orbital analyses are performed to reveal the underlying interaction mechanisms, showing that electrostatic interactions as well as the donation and back donation of electrons between the transition metal ions and the CO2 molecules play a key role in the capture.

Electrostatics-mediated α-chymotrypsin inhibition by functionalized single-walled carbon nanotubes.

PubMed

Zhao, Daohui; Zhou, Jian

2017-01-04

The α-chymotrypsin (α-ChT) enzyme is extensively used for studying nanomaterial-induced enzymatic activity inhibition. A recent experimental study reported that carboxylized carbon nanotubes (CNTs) played an important role in regulating the α-ChT activity. In this study, parallel tempering Monte Carlo and molecular dynamics simulations were combined to elucidate the interactions between α-ChT and CNTs in relation to the CNT functional group density. The simulation results indicate that the adsorption and the driving force of α-ChT on different CNTs are contingent on the carboxyl density. Meanwhile, minor secondary structural changes are observed in adsorption processes. It is revealed that α-ChT interacts with pristine CNTs through hydrophobic forces and exhibits a non-competitive characteristic with the active site facing towards the solution; while it binds to carboxylized CNTs with the active pocket through a dominant electrostatic association, which causes enzymatic activity inhibition in a competitive-like mode. These findings are in line with experimental results, and well interpret the activity inhibition of α-ChT at the molecular level. Moreover, this study would shed light on the detailed mechanism of specific recognition and regulation of α-ChT by other functionalized nanomaterials.

Influence of organic surface coatings on the sorption of anticonvulsants on mineral surfaces.

PubMed

Qu, Shen; Cwiertny, David M

2013-10-01

Here, we explore the role that sorption to mineral surfaces plays in the fate of two commonly encountered effluent-derived pharmaceuticals, the anticonvulsants phenytoin and carbamazepine. Adsorption isotherms and pH-edge experiments are consistent with electrostatics governing anticonvulsant uptake on metal oxides typically found in soil and aquifer material (e.g., Si, Al, Fe, Mn, and Ti). Appreciable, albeit limited, adsorption was observed only for phenytoin, which is anionic above pH 8.3, on the iron oxides hematite and ferrihydrite. Adsorption increased substantially in the presence of cationic and anionic surfactants, species also commonly encountered in wastewater effluent. For carbamazepine, we propose the enhanced uptake results entirely from hydrophobic interactions with apolar tails of surfactant surface coatings. For phenytoin, adsorption also arises from the ability of surfactants to alter the net charge of the mineral surface and thereby further enhance favorable electrostatic interactions with its anionic form. Collectively, our results demonstrate that although pristine mineral surfaces are likely not major sinks for phenytoin and carbamazepine in the environment, their alteration with organic matter, particularly surfactants, can considerably increase their ability to retain these emerging pollutants in subsurface systems.

Two dimensional kinetic analysis of electrostatic harmonic plasma waves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fonseca-Pongutá, E. C.; Ziebell, L. F.; Gaelzer, R.

2016-06-15

Electrostatic harmonic Langmuir waves are virtual modes excited in weakly turbulent plasmas, first observed in early laboratory beam-plasma experiments as well as in rocket-borne active experiments in space. However, their unequivocal presence was confirmed through computer simulated experiments and subsequently theoretically explained. The peculiarity of harmonic Langmuir waves is that while their existence requires nonlinear response, their excitation mechanism and subsequent early time evolution are governed by essentially linear process. One of the unresolved theoretical issues regards the role of nonlinear wave-particle interaction process over longer evolution time period. Another outstanding issue is that existing theories for these modes aremore » limited to one-dimensional space. The present paper carries out two dimensional theoretical analysis of fundamental and (first) harmonic Langmuir waves for the first time. The result shows that harmonic Langmuir wave is essentially governed by (quasi)linear process and that nonlinear wave-particle interaction plays no significant role in the time evolution of the wave spectrum. The numerical solutions of the two-dimensional wave spectra for fundamental and harmonic Langmuir waves are also found to be consistent with those obtained by direct particle-in-cell simulation method reported in the literature.« less

Efficiency determination of an electrostatic lunar dust collector by discrete element method

NASA Astrophysics Data System (ADS)

Afshar-Mohajer, Nima; Wu, Chang-Yu; Sorloaica-Hickman, Nicoleta

2012-07-01

Lunar grains become charged by the sun's radiation in the tenuous atmosphere of the moon. This leads to lunar dust levitation and particle deposition which often create serious problems in the costly system deployed in lunar exploration. In this study, an electrostatic lunar dust collector (ELDC) is proposed to address the issue and the discrete element method (DEM) is used to investigate the effects of electrical particle-particle interactions, non-uniformity of the electrostatic field, and characteristics of the ELDC. The simulations on 20-μm-sized lunar particles reveal the electrical particle-particle interactions of the dust particles within the ELDC plates require 29% higher electrostatic field strength than that without the interactions for 100% collection efficiency. For the given ELDC geometry, consideration of non-uniformity of the electrostatic field along with electrical interactions between particles on the same ELDC geometry leads to a higher requirement of ˜3.5 kV/m to ensure 100% particle collection. Notably, such an electrostatic field is about 103 times less than required for electrodynamic self-cleaning methods. Finally, it is shown for a "half-size" system that the DEM model predicts greater collection efficiency than the Eulerian-based model at all voltages less than required for 100% efficiency. Halving the ELDC dimensions boosts the particle concentration inside the ELDC, as well as the resulting field strength for a given voltage. Though a lunar photovoltaic system was the subject, the results of this study are useful for evaluation of any system for collecting charged particles in other high vacuum environment using an electrostatic field.

Electrostatic effects in unfolded staphylococcal nuclease

PubMed Central

Fitzkee, Nicholas C.; García-Moreno E, Bertrand

2008-01-01

Structure-based calculations of pK a values and electrostatic free energies of proteins assume that electrostatic effects in the unfolded state are negligible. In light of experimental evidence showing that this assumption is invalid for many proteins, and with increasing awareness that the unfolded state is more structured and compact than previously thought, a detailed examination of electrostatic effects in unfolded proteins is warranted. Here we address this issue with structure-based calculations of electrostatic interactions in unfolded staphylococcal nuclease. The approach involves the generation of ensembles of structures representing the unfolded state, and calculation of Coulomb energies to Boltzmann weight the unfolded state ensembles. Four different structural models of the unfolded state were tested. Experimental proton binding data measured with a variant of nuclease that is unfolded under native conditions were used to establish the validity of the calculations. These calculations suggest that weak Coulomb interactions are an unavoidable property of unfolded proteins. At neutral pH, the interactions are too weak to organize the unfolded state; however, at extreme pH values, where the protein has a significant net charge, the combined action of a large number of weak repulsive interactions can lead to the expansion of the unfolded state. The calculated pK a values of ionizable groups in the unfolded state are similar but not identical to the values in small peptides in water. These studies suggest that the accuracy of structure-based calculations of electrostatic contributions to stability cannot be improved unless electrostatic effects in the unfolded state are calculated explicitly. PMID:18227429

First-principles simulations of electrostatic interactions between dust grains

NASA Astrophysics Data System (ADS)

Itou, H.; Amano, T.; Hoshino, M.

2014-12-01

We investigated the electrostatic interaction between two identical dust grains of an infinite mass immersed in homogeneous plasma by employing first-principles N-body simulations combined with the Ewald method. We specifically tested the possibility of an attractive force due to overlapping Debye spheres (ODSs), as was suggested by Resendes et al. [Phys. Lett. A 239, 181-186 (1998)]. Our simulation results demonstrate that the electrostatic interaction is repulsive and even stronger than the standard Yukawa potential. We showed that the measured electric field acting on the grain is highly consistent with a model electrostatic potential around a single isolated grain that takes into account a correction due to the orbital motion limited theory. Our result is qualitatively consistent with the counterargument suggested by Markes and Williams [Phys. Lett. A 278, 152-158 (2000)], indicating the absence of the ODS attractive force.

Interaction between Stray Electrostatic Fields and a Charged Free-Falling Test Mass

NASA Astrophysics Data System (ADS)

Antonucci, F.; Cavalleri, A.; Dolesi, R.; Hueller, M.; Nicolodi, D.; Tu, H. B.; Vitale, S.; Weber, W. J.

2012-05-01

We present an experimental analysis of force noise caused by stray electrostatic fields acting on a charged test mass inside a conducting enclosure, a key problem for precise gravitational experiments. Measurement of the average field that couples to the test mass charge, and its fluctuations, is performed with two independent torsion pendulum techniques, including direct measurement of the forces caused by a change in electrostatic charge. We analyze the problem with an improved electrostatic model that, coupled with the experimental data, also indicates how to correctly measure and null the stray field that interacts with the test mass charge. Our measurements allow a conservative upper limit on acceleration noise, of 2(fm/s2)/Hz1/2 for frequencies above 0.1 mHz, for the interaction between stray fields and charge in the LISA gravitational wave mission.

Regulation of activation and processing of the cystic fibrosis transmembrane conductance regulator (CFTR) by a complex electrostatic interaction between the regulatory domain and cytoplasmic loop 3.

PubMed

Wang, Guangyu; Duan, Dayue Darrel

2012-11-23

NEG2 regulates CFTR gating but the mechanism is unknown. A putative NEG2-CL3 electrostatic attraction, possibly weakened by Arg-764/Arg-766 of the R domain, prohibited CFTR activation. A charge exchange between NEG2 and CL3 caused misprocessing. Electrostatic regulation of CFTR activation and processing may be asymmetric at the CL3-R interface. The CL3-R interface is optimally designed for multiple regulations of CFTR functions. NEG2, a short C-terminal segment (817-838) of the unique regulatory (R) domain of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, has been reported to regulate CFTR gating in response to cAMP-dependent R domain phosphorylation. The underlying mechanism, however, is unclear. Here, Lys-946 of cytoplasmic loop 3 (CL3) is proposed as counter-ion of Asp-835, Asp-836, or Glu-838 of NEG2 to prevent the channel activation by PKA. Arg-764 or Arg-766 of the Ser-768 phosphorylation site of the R domain is proposed to promote the channel activation possibly by weakening the putative CL3-NEG2 electrostatic attraction. First, not only D835A, D836A, and E838A but also K946A reduced the PKA-dependent CFTR activation. Second, both K946D and D835R/D836R/E838R mutants were activated by ATP and curcumin to a different extent. Third, R764A and R766A mutants enhanced the PKA-dependent activation. However, it is very exciting that D835R/D836R/E838R and K946D/H950D and H950R exhibited normal channel processing and activity whereas D835R/D836R/E838R/K946D/H950D was fractionally misprocessed and silent in response to forskolin. Further, D836R and E838R played a critical role in the asymmetric electrostatic regulation of CFTR processing, and Ser-768 phosphorylation may not be involved. Thus, a complex interfacial interaction among CL3, NEG2, and the Ser-768 phosphorylation site may be responsible for the asymmetric electrostatic regulation of CFTR activation and processing.

Perspectives on electrostatics and conformational motions in enzyme catalysis.

PubMed

Hanoian, Philip; Liu, C Tony; Hammes-Schiffer, Sharon; Benkovic, Stephen

2015-02-17

CONSPECTUS: Enzymes are essential for all living organisms, and their effectiveness as chemical catalysts has driven more than a half century of research seeking to understand the enormous rate enhancements they provide. Nevertheless, a complete understanding of the factors that govern the rate enhancements and selectivities of enzymes remains elusive, due to the extraordinary complexity and cooperativity that are the hallmarks of these biomolecules. We have used a combination of site-directed mutagenesis, pre-steady-state kinetics, X-ray crystallography, nuclear magnetic resonance (NMR), vibrational and fluorescence spectroscopies, resonance energy transfer, and computer simulations to study the implications of conformational motions and electrostatic interactions on enzyme catalysis in the enzyme dihydrofolate reductase (DHFR). We have demonstrated that modest equilibrium conformational changes are functionally related to the hydride transfer reaction. Results obtained for mutant DHFRs illustrated that reductions in hydride transfer rates are correlated with altered conformational motions, and analysis of the evolutionary history of DHFR indicated that mutations appear to have occurred to preserve both the hydride transfer rate and the associated conformational changes. More recent results suggested that differences in local electrostatic environments contribute to finely tuning the substrate pKa in the initial protonation step. Using a combination of primary and solvent kinetic isotope effects, we demonstrated that the reaction mechanism is consistent across a broad pH range, and computer simulations suggested that deprotonation of the active site Tyr100 may play a crucial role in substrate protonation at high pH. Site-specific incorporation of vibrational thiocyanate probes into the ecDHFR active site provided an experimental tool for interrogating these microenvironments and for investigating changes in electrostatics along the DHFR catalytic cycle. Complementary molecular dynamics simulations in conjunction with mixed quantum mechanical/molecular mechanical calculations accurately reproduced the vibrational frequency shifts in these probes and provided atomic-level insight into the residues influencing these changes. Our findings indicate that conformational and electrostatic changes are intimately related and functionally essential. This approach can be readily extended to the study of other enzyme systems to identify more general trends in the relationship between conformational fluctuations and electrostatic interactions. These results are relevant to researchers seeking to design novel enzymes as well as those seeking to develop therapeutic agents that function as enzyme inhibitors.

Perspectives on Electrostatics and Conformational Motions in Enzyme Catalysis

PubMed Central

2016-01-01

Conspectus Enzymes are essential for all living organisms, and their effectiveness as chemical catalysts has driven more than a half century of research seeking to understand the enormous rate enhancements they provide. Nevertheless, a complete understanding of the factors that govern the rate enhancements and selectivities of enzymes remains elusive, due to the extraordinary complexity and cooperativity that are the hallmarks of these biomolecules. We have used a combination of site-directed mutagenesis, pre-steady-state kinetics, X-ray crystallography, nuclear magnetic resonance (NMR), vibrational and fluorescence spectroscopies, resonance energy transfer, and computer simulations to study the implications of conformational motions and electrostatic interactions on enzyme catalysis in the enzyme dihydrofolate reductase (DHFR). We have demonstrated that modest equilibrium conformational changes are functionally related to the hydride transfer reaction. Results obtained for mutant DHFRs illustrated that reductions in hydride transfer rates are correlated with altered conformational motions, and analysis of the evolutionary history of DHFR indicated that mutations appear to have occurred to preserve both the hydride transfer rate and the associated conformational changes. More recent results suggested that differences in local electrostatic environments contribute to finely tuning the substrate pKa in the initial protonation step. Using a combination of primary and solvent kinetic isotope effects, we demonstrated that the reaction mechanism is consistent across a broad pH range, and computer simulations suggested that deprotonation of the active site Tyr100 may play a crucial role in substrate protonation at high pH. Site-specific incorporation of vibrational thiocyanate probes into the ecDHFR active site provided an experimental tool for interrogating these microenvironments and for investigating changes in electrostatics along the DHFR catalytic cycle. Complementary molecular dynamics simulations in conjunction with mixed quantum mechanical/molecular mechanical calculations accurately reproduced the vibrational frequency shifts in these probes and provided atomic-level insight into the residues influencing these changes. Our findings indicate that conformational and electrostatic changes are intimately related and functionally essential. This approach can be readily extended to the study of other enzyme systems to identify more general trends in the relationship between conformational fluctuations and electrostatic interactions. These results are relevant to researchers seeking to design novel enzymes as well as those seeking to develop therapeutic agents that function as enzyme inhibitors. PMID:25565178

Electrostatic Steering Accelerates C3d:CR2 Association

PubMed Central

2016-01-01

Electrostatic effects are ubiquitous in protein interactions and are found to be pervasive in the complement system as well. The interaction between complement fragment C3d and complement receptor 2 (CR2) has evolved to become a link between innate and adaptive immunity. Electrostatic interactions have been suggested to be the driving factor for the association of the C3d:CR2 complex. In this study, we investigate the effects of ionic strength and mutagenesis on the association of C3d:CR2 through Brownian dynamics simulations. We demonstrate that the formation of the C3d:CR2 complex is ionic strength-dependent, suggesting the presence of long-range electrostatic steering that accelerates the complex formation. Electrostatic steering occurs through the interaction of an acidic surface patch in C3d and the positively charged CR2 and is supported by the effects of mutations within the acidic patch of C3d that slow or diminish association. Our data are in agreement with previous experimental mutagenesis and binding studies and computational studies. Although the C3d acidic patch may be locally destabilizing because of unfavorable Coulombic interactions of like charges, it contributes to the acceleration of association. Therefore, acceleration of function through electrostatic steering takes precedence to stability. The site of interaction between C3d and CR2 has been the target for delivery of CR2-bound nanoparticle, antibody, and small molecule biomarkers, as well as potential therapeutics. A detailed knowledge of the physicochemical basis of C3d:CR2 association may be necessary to accelerate biomarker and drug discovery efforts. PMID:27092816

The two sides of complement C3d: evolution of electrostatics in a link between innate and adaptive immunity.

PubMed

Kieslich, Chris A; Morikis, Dimitrios

2012-01-01

The interaction between complement fragment C3d and complement receptor 2 (CR2) is a key aspect of complement immune system activation, and is a component in a link between innate and adaptive immunities. The complement immune system is an ancient mechanism for defense, and can be found in species that have been on Earth for the last 600 million years. However, the link between the complement system and adaptive immunity, which is formed through the association of the B-cell co-receptor complex, including the C3d-CR2 interaction, is a much more recent adaptation. Human C3d and CR2 have net charges of -1 and +7 respectively, and are believed to have evolved favoring the role of electrostatics in their functions. To investigate the role of electrostatics in the function and evolution of human C3d and CR2, we have applied electrostatic similarity methods to identify regions of evolutionarily conserved electrostatic potential based on 24 homologues of complement C3d and 4 homologues of CR2. We also examine the effects of structural perturbation, as introduced through molecular dynamics and mutations, on spatial distributions of electrostatic potential to identify perturbation resistant regions, generated by so-called electrostatic "hot-spots". Distributions of electrostatic similarity based on families of perturbed structures illustrate the presence of electrostatic "hot-spots" at the two functional sites of C3d, while the surface of CR2 lacks electrostatic "hot-spots" despite its excessively positive nature. We propose that the electrostatic "hot-spots" of C3d have evolved to optimize its dual-functionality (covalently attaching to pathogen surfaces and interaction with CR2), which are both necessary for the formation B-cell co-receptor complexes. Comparison of the perturbation resistance of the electrostatic character of the homologues of C3d suggests that there was an emergence of a new role of electrostatics, and a transition in the function of C3d, after the divergence of jawless fish.

The Two Sides of Complement C3d: Evolution of Electrostatics in a Link between Innate and Adaptive Immunity

PubMed Central

Kieslich, Chris A.; Morikis, Dimitrios

2012-01-01

The interaction between complement fragment C3d and complement receptor 2 (CR2) is a key aspect of complement immune system activation, and is a component in a link between innate and adaptive immunities. The complement immune system is an ancient mechanism for defense, and can be found in species that have been on Earth for the last 600 million years. However, the link between the complement system and adaptive immunity, which is formed through the association of the B-cell co-receptor complex, including the C3d-CR2 interaction, is a much more recent adaptation. Human C3d and CR2 have net charges of −1 and +7 respectively, and are believed to have evolved favoring the role of electrostatics in their functions. To investigate the role of electrostatics in the function and evolution of human C3d and CR2, we have applied electrostatic similarity methods to identify regions of evolutionarily conserved electrostatic potential based on 24 homologues of complement C3d and 4 homologues of CR2. We also examine the effects of structural perturbation, as introduced through molecular dynamics and mutations, on spatial distributions of electrostatic potential to identify perturbation resistant regions, generated by so-called electrostatic “hot-spots”. Distributions of electrostatic similarity based on families of perturbed structures illustrate the presence of electrostatic “hot-spots” at the two functional sites of C3d, while the surface of CR2 lacks electrostatic “hot-spots” despite its excessively positive nature. We propose that the electrostatic “hot-spots” of C3d have evolved to optimize its dual-functionality (covalently attaching to pathogen surfaces and interaction with CR2), which are both necessary for the formation B-cell co-receptor complexes. Comparison of the perturbation resistance of the electrostatic character of the homologues of C3d suggests that there was an emergence of a new role of electrostatics, and a transition in the function of C3d, after the divergence of jawless fish. PMID:23300422

Biomolecular electrostatics and solvation: a computational perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ren, Pengyu; Chun, Jaehun; Thomas, Dennis G.

2012-11-01

An understanding of molecular interactions is essential for insight into biological systems at the molecular scale. Among the various components of molecular interactions, electrostatics are of special importance because of their long-range nature and their influence on polar or charged molecules, including water, aqueous ions, proteins, nucleic acids, carbohydrates, and membrane lipids. In particular, robust models of electrostatic interactions are essential for understanding the solvation properties of biomolecules and the effects of solvation upon biomolecular folding, binding, enzyme catalysis and dynamics. Electrostatics, therefore, are of central importance to understanding biomolecular structure and modeling interactions within and among biological molecules. Thismore » review discusses the solvation of biomolecules with a computational biophysics view towards describing the phenomenon. While our main focus lies on the computational aspect of the models, we summarize the common characteristics of biomolecular solvation (e.g., solvent structure, polarization, ion binding, and nonpolar behavior) in order to provide reasonable backgrounds to understand the solvation models.« less

Biomolecular electrostatics and solvation: a computational perspective

PubMed Central

Ren, Pengyu; Chun, Jaehun; Thomas, Dennis G.; Schnieders, Michael J.; Marucho, Marcelo; Zhang, Jiajing; Baker, Nathan A.

2012-01-01

An understanding of molecular interactions is essential for insight into biological systems at the molecular scale. Among the various components of molecular interactions, electrostatics are of special importance because of their long-range nature and their influence on polar or charged molecules, including water, aqueous ions, proteins, nucleic acids, carbohydrates, and membrane lipids. In particular, robust models of electrostatic interactions are essential for understanding the solvation properties of biomolecules and the effects of solvation upon biomolecular folding, binding, enzyme catalysis, and dynamics. Electrostatics, therefore, are of central importance to understanding biomolecular structure and modeling interactions within and among biological molecules. This review discusses the solvation of biomolecules with a computational biophysics view towards describing the phenomenon. While our main focus lies on the computational aspect of the models, we provide an overview of the basic elements of biomolecular solvation (e.g., solvent structure, polarization, ion binding, and nonpolar behavior) in order to provide a background to understand the different types of solvation models. PMID:23217364

Biomolecular electrostatics and solvation: a computational perspective.

PubMed

Ren, Pengyu; Chun, Jaehun; Thomas, Dennis G; Schnieders, Michael J; Marucho, Marcelo; Zhang, Jiajing; Baker, Nathan A

2012-11-01

An understanding of molecular interactions is essential for insight into biological systems at the molecular scale. Among the various components of molecular interactions, electrostatics are of special importance because of their long-range nature and their influence on polar or charged molecules, including water, aqueous ions, proteins, nucleic acids, carbohydrates, and membrane lipids. In particular, robust models of electrostatic interactions are essential for understanding the solvation properties of biomolecules and the effects of solvation upon biomolecular folding, binding, enzyme catalysis, and dynamics. Electrostatics, therefore, are of central importance to understanding biomolecular structure and modeling interactions within and among biological molecules. This review discusses the solvation of biomolecules with a computational biophysics view toward describing the phenomenon. While our main focus lies on the computational aspect of the models, we provide an overview of the basic elements of biomolecular solvation (e.g. solvent structure, polarization, ion binding, and non-polar behavior) in order to provide a background to understand the different types of solvation models.

Effects of protein conformational motions in the native form and non-uniform distribution of electrostatic interaction sites on interfacial water

NASA Astrophysics Data System (ADS)

Pal, Somedatta; Bandyopadhyay, Sanjoy

2013-07-01

Protein-water interactions and their influence on surrounding water is a long-standing problem. Despite its importance, the origin of differential water behavior at the protein surface is still elusive. We have performed molecular simulations of the protein barstar in aqueous medium. Efforts have been made to explore how the conformational motions of the protein segments in the native form and the heterogeneous electrostatic interactions with the polar and charged groups of the protein affect the interfacial water properties. The calculations reveal that reduced dimension of the hydration layer on freezing the protein's degrees of freedom does not modify the heterogeneous water distributions around the protein. However, turning off the protein-water electrostatic contribution leads to non-preferential near-uniform water arrangements at the surface. It is further shown that with protein-water electrostatic interactions turned on, the local structuring of water molecules around the segments are correlated with their degree of exposure to the solvent.

Activation of the SN2 Reaction by Adjacent π Systems: The Critical Role of Electrostatic Interactions and of Dissociative Character.

PubMed

Robiette, Raphaël; Trieu-Van, Tran; Aggarwal, Varinder K; Harvey, Jeremy N

2016-01-27

The activation of the SN2 reaction by π systems is well documented in textbooks. It has been shown previously that this is not primarily due to classical (hyper)conjugative effects. Instead, π-conjugated substituents enhance favorable substrate-nucleophile electrostatic interactions, with electron-withdrawing groups (EWG) on the sp(2) system leading to even stronger activation. Herein we report computational and experimental results which show that this activation by sp(2) EWG-substitution only occurs in a fairly limited number of cases, when the nucleophile involves strong electrostatic interactions (usually strongly basic negatively charged nucleophiles). In other cases, where bond breaking is more advanced than bond making at the transition state, electrophile-nucleophile electrostatic interactions are less important. In such cases, (hyper)conjugative electronic effects determine the reactivity, and EWG-substitution leads to decreased reactivity. The basicity of the nucleophile as well as solvent effects can help to determine which of these two regimes occurs for a given electrophile.

Electrostatic orientation of the electron-transfer complex between plastocyanin and cytochrome c.

PubMed

Roberts, V A; Freeman, H C; Olson, A J; Tainer, J A; Getzoff, E D

1991-07-15

To understand the specificity and efficiency of protein-protein interactions promoting electron transfer, we evaluated the role of electrostatic forces in precollision orientation by the development of two new methods, computer graphics alignment of protein electrostatic fields and a systematic orientational search of intermolecular electrostatic energies for two proteins at present separation distances. We applied these methods to the plastocyanin/cytochrome c interaction, which is faster than random collision, but too slow for study by molecular dynamics techniques. Significant electrostatic potentials were concentrated on one-fourth (969 A2) of the plastocyanin surface, with the greatest negative potential centered on the Tyr-83 hydroxyl within the acidic patch, and on one-eighth (632 A2) of the cytochrome c surface, with the greatest positive potential centered near the exposed heme edge. Coherent electrostatic fields occurred only over these regions, suggesting that local, rather than global, charge complementarity controls productive recognition. The three energetically favored families of pre-collision orientations all directed the positive region surrounding the heme edge of cytochrome c toward the acidic patch of plastocyanin but differed in heme plane orientation. Analysis of electrostatic fields, electrostatic energies of precollision orientations with 12 and 6 A separation distances, and surface topographies suggested that the favored orientations should converge to productive complexes promoting a single electron-transfer pathway from the cytochrome c heme edge to Tyr-83 of plastocyanin. Direct interactions of the exposed Cu ligand in plastocyanin with the cytochrome c heme edge are not unfavorable sterically or electrostatically but should occur no faster than randomly, indicating that this is not the primary pathway for electron transfer.

3D RISM theory with fast reciprocal-space electrostatics.

PubMed

Heil, Jochen; Kast, Stefan M

2015-03-21

The calculation of electrostatic solute-solvent interactions in 3D RISM ("three-dimensional reference interaction site model") integral equation theory is recast in a form that allows for a computational treatment analogous to the "particle-mesh Ewald" formalism as used for molecular simulations. In addition, relations that connect 3D RISM correlation functions and interaction potentials with thermodynamic quantities such as the chemical potential and average solute-solvent interaction energy are reformulated in a way that calculations of expensive real-space electrostatic terms on the 3D grid are completely avoided. These methodical enhancements allow for both, a significant speedup particularly for large solute systems and a smoother convergence of predicted thermodynamic quantities with respect to box size, as illustrated for several benchmark systems.

Limits of applicability of the quasilinear approximation to the electrostatic wave-plasma interaction

NASA Astrophysics Data System (ADS)

Zacharegkas, Georgios; Isliker, Heinz; Vlahos, Loukas

2016-11-01

The limitation of the Quasilinear Theory (QLT) to describe the diffusion of electrons and ions in velocity space when interacting with a spectrum of large amplitude electrostatic Langmuir, Upper and Lower hybrid waves, is analyzed. We analytically and numerically estimate the threshold for the amplitude of the waves above which the QLT breaks down, using a test particle code. The evolution of the velocity distribution, the velocity-space diffusion coefficients, the driven current, and the heating of the particles are investigated, for the interaction with small and large amplitude electrostatic waves, that is, in both regimes, where QLT is valid and where it clearly breaks down.

Carbohydrate–Aromatic Interactions in Proteins

PubMed Central

2015-01-01

Protein–carbohydrate interactions play pivotal roles in health and disease. However, defining and manipulating these interactions has been hindered by an incomplete understanding of the underlying fundamental forces. To elucidate common and discriminating features in carbohydrate recognition, we have analyzed quantitatively X-ray crystal structures of proteins with noncovalently bound carbohydrates. Within the carbohydrate-binding pockets, aliphatic hydrophobic residues are disfavored, whereas aromatic side chains are enriched. The greatest preference is for tryptophan with an increased prevalence of 9-fold. Variations in the spatial orientation of amino acids around different monosaccharides indicate specific carbohydrate C–H bonds interact preferentially with aromatic residues. These preferences are consistent with the electronic properties of both the carbohydrate C–H bonds and the aromatic residues. Those carbohydrates that present patches of electropositive saccharide C–H bonds engage more often in CH−π interactions involving electron-rich aromatic partners. These electronic effects are also manifested when carbohydrate–aromatic interactions are monitored in solution: NMR analysis indicates that indole favorably binds to electron-poor C–H bonds of model carbohydrates, and a clear linear free energy relationships with substituted indoles supports the importance of complementary electronic effects in driving protein–carbohydrate interactions. Together, our data indicate that electrostatic and electronic complementarity between carbohydrates and aromatic residues play key roles in driving protein–carbohydrate complexation. Moreover, these weak noncovalent interactions influence which saccharide residues bind to proteins, and how they are positioned within carbohydrate-binding sites. PMID:26561965

Carbohydrate-Aromatic Interactions in Proteins.

PubMed

Hudson, Kieran L; Bartlett, Gail J; Diehl, Roger C; Agirre, Jon; Gallagher, Timothy; Kiessling, Laura L; Woolfson, Derek N

2015-12-09

Protein-carbohydrate interactions play pivotal roles in health and disease. However, defining and manipulating these interactions has been hindered by an incomplete understanding of the underlying fundamental forces. To elucidate common and discriminating features in carbohydrate recognition, we have analyzed quantitatively X-ray crystal structures of proteins with noncovalently bound carbohydrates. Within the carbohydrate-binding pockets, aliphatic hydrophobic residues are disfavored, whereas aromatic side chains are enriched. The greatest preference is for tryptophan with an increased prevalence of 9-fold. Variations in the spatial orientation of amino acids around different monosaccharides indicate specific carbohydrate C-H bonds interact preferentially with aromatic residues. These preferences are consistent with the electronic properties of both the carbohydrate C-H bonds and the aromatic residues. Those carbohydrates that present patches of electropositive saccharide C-H bonds engage more often in CH-π interactions involving electron-rich aromatic partners. These electronic effects are also manifested when carbohydrate-aromatic interactions are monitored in solution: NMR analysis indicates that indole favorably binds to electron-poor C-H bonds of model carbohydrates, and a clear linear free energy relationships with substituted indoles supports the importance of complementary electronic effects in driving protein-carbohydrate interactions. Together, our data indicate that electrostatic and electronic complementarity between carbohydrates and aromatic residues play key roles in driving protein-carbohydrate complexation. Moreover, these weak noncovalent interactions influence which saccharide residues bind to proteins, and how they are positioned within carbohydrate-binding sites.

Intermolecular interactions and aggregation of fac-tris(2-phenylpyridinato-C2,N)iridium(III) in nonpolar solvents.

PubMed

Takayasu, Satoshi; Suzuki, Takayoshi; Shinozaki, Kazuteru

2013-08-15

The intermolecular interaction and aggregation of the neutral complex fac-tris(2-phenylpyridinato-C(2),N)iridium(III) (fac-Ir(ppy)3) in solution was investigated. Intermolecular interactions were found to effectively decrease the luminescence lifetime via self-quenching with increasing fac-Ir(ppy)3 concentrations. A Stern-Volmer plot for quenching in acetonitrile was linear, due to bimolecular self-quenching, but curved in toluene as the result of excimer formation. (1)H NMR spectra demonstrated a monomer-aggregate equilibrium which resulted in spectral shifts depending on solvent polarity. X-ray crystallography provided structural information concerning the aggregate, which is based on a tetramer consisting of two Δ-fac-Ir(ppy)3-Λ-fac-Ir(ppy)3 pairs. Offset π-π stacking of ppy ligands and electrostatic dipole-dipole interactions between complex molecules play an important role in the formation of these molecular pairs.

Energy component analysis of π interactions.

PubMed

Sherrill, C David

2013-04-16

Fundamental features of biomolecules, such as their structure, solvation, and crystal packing and even the docking of drugs, rely on noncovalent interactions. Theory can help elucidate the nature of these interactions, and energy component analysis reveals the contributions from the various intermolecular forces: electrostatics, London dispersion terms, induction (polarization), and short-range exchange-repulsion. Symmetry-adapted perturbation theory (SAPT) provides one method for this type of analysis. In this Account, we show several examples of how SAPT provides insight into the nature of noncovalent π-interactions. In cation-π interactions, the cation strongly polarizes electrons in π-orbitals, leading to substantially attractive induction terms. This polarization is so important that a cation and a benzene attract each other when placed in the same plane, even though a consideration of the electrostatic interactions alone would suggest otherwise. SAPT analysis can also support an understanding of substituent effects in π-π interactions. Trends in face-to-face sandwich benzene dimers cannot be understood solely in terms of electrostatic effects, especially for multiply substituted dimers, but SAPT analysis demonstrates the importance of London dispersion forces. Moreover, detailed SAPT studies also reveal the critical importance of charge penetration effects in π-stacking interactions. These effects arise in cases with substantial orbital overlap, such as in π-stacking in DNA or in crystal structures of π-conjugated materials. These charge penetration effects lead to attractive electrostatic terms where a simpler analysis based on atom-centered charges, electrostatic potential plots, or even distributed multipole analysis would incorrectly predict repulsive electrostatics. SAPT analysis of sandwich benzene, benzene-pyridine, and pyridine dimers indicates that dipole/induced-dipole terms present in benzene-pyridine but not in benzene dimer are relatively unimportant. In general, a nitrogen heteroatom contracts the electron density, reducing the magnitude of both the London dispersion and the exchange-repulsion terms, but with an overall net increase in attraction. Finally, using recent advances in SAPT algorithms, researchers can now perform SAPT computations on systems with 200 atoms or more. We discuss a recent study of the intercalation complex of proflavine with a trinucleotide duplex of DNA. Here, London dispersion forces are the strongest contributors to binding, as is typical for π-π interactions. However, the electrostatic terms are larger than usual on a fractional basis, which likely results from the positive charge on the intercalator and its location between two electron-rich base pairs. These cation-π interactions also increase the induction term beyond those of typical noncovalent π-interactions.

Molecular dynamics simulations of low-ordered alzheimer β-amyloid oligomers from dimer to hexamer on self-assembled monolayers.

PubMed

Zhao, Jun; Wang, Qiuming; Liang, Guizhao; Zheng, Jie

2011-12-20

Accumulation of small soluble oligomers of amyloid-β (Aβ) in the human brain is thought to play an important pathological role in Alzheimer's disease. The interaction of these Aβ oligomers with cell membrane and other artificial surfaces is important for the understanding of Aβ aggregation and toxicity mechanisms. Here, we present a series of exploratory molecular dynamics (MD) simulations to study the early adsorption and conformational change of Aβ oligomers from dimer to hexamer on three different self-assembled monolayers (SAMs) terminated with CH(3), OH, and COOH groups. Within the time scale of MD simulations, the conformation, orientation, and adsorption of Aβ oligomers on the SAMs is determined by complex interplay among the size of Aβ oligomers, the surface chemistry of the SAMs, and the structure and dynamics of interfacial waters. Energetic analysis of Aβ adsorption on the SAMs reveals that Aβ adsorption on the SAMs is a net outcome of different competitions between dominant hydrophobic Aβ-CH(3)-SAM interactions and weak CH(3)-SAM-water interactions, between dominant electrostatic Aβ-COOH-SAM interactions and strong COOH-SAM-water interactions, and between comparable hydrophobic and electrostatic Aβ-OH-SAM interactions and strong OH-SAM-water interactions. Atomic force microscopy images also confirm that all of three SAMs can induce the adsorption and polymerization of Aβ oligomers. Structural analysis of Aβ oligomers on the SAMs shows a dramatic increase in structural stability and β-sheet content from dimer to trimer, suggesting that Aβ trimer could act as seeds for Aβ polymerization on the SAMs. This work provides atomic-level understanding of Aβ peptides at interface. © 2011 American Chemical Society

Nitroimidazoles adsorption on activated carbon cloth from aqueous solution.

PubMed

Ocampo-Pérez, R; Orellana-Garcia, F; Sánchez-Polo, M; Rivera-Utrilla, J; Velo-Gala, I; López-Ramón, M V; Alvarez-Merino, M A

2013-07-01

The objective of this study was to analyze the equilibrium and adsorption kinetics of nitroimidazoles on activated carbon cloth (ACC), determining the main interactions responsible for the adsorption process and the diffusion mechanism of these compounds on this material. The influence of the different operational variables, such as ionic strength, pH, temperature, and type of water (ultrapure, surface, and waste), was also studied. The results obtained show that the ACC has a high capacity to adsorb nitroimidazoles in aqueous solution. Electrostatic interactions play an important role at pH<3, which favors the repulsive forces between dimetridazole or metronidazole and the ACC surface. The formation of hydrogen bonds and dispersive interactions play the predominant role at higher pH values. Modifications of the ACC with NH3, K2S2O8, and O3 demonstrated that its surface chemistry plays a predominant role in nitroimidazole adsorption on this material. The adsorption capacity of ACC is considerably high in surface waters and reduced in urban wastewater, due to the levels of alkalinity and dissolved organic matter present in the different types of water. Finally, the results of applying kinetic models revealed that the global adsorption rate of dimetridazole and metronidazole is controlled by intraparticle diffusion. Copyright © 2013 Elsevier Inc. All rights reserved.

The effect of desulfation of chondroitin sulfate on interactions with positively charged growth factors and upregulation of cartilaginous markers in encapsulated MSCs.

PubMed

Lim, Jeremy J; Temenoff, Johnna S

2013-07-01

Sulfated glycosaminoglycans (GAGs) are known to interact electrostatically with positively charged growth factors to modulate signaling. Therefore, regulating the degree of sulfation of GAGs may be a promising approach to tailor biomaterial carriers for controlled growth factor delivery and release. For this study, chondroitin sulfate (CS) was first desulfated to form chondroitin, and resulting crosslinked CS and chondroitin hydrogels were examined in vitro for release of positively charged model protein (histone) and for their effect on cartilaginous differentiation of encapsulated human mesenchymal stem cells (MSCs). Desulfation significantly increased the release of histone from chondroitin hydrogels (30.6 ± 2.3 μg released over 8 days, compared to natively sulfated CS with 20.2 ± 0.8 μg), suggesting that sulfation alone plays a significant role in modulating protein interactions with GAG hydrogels. MSCs in chondroitin hydrogels significantly upregulated gene expression of collagen II and aggrecan by day 21 in chondrogenic medium (115 ± 100 and 23.1 ± 7.9 fold upregulation of collagen II and aggrecan, respectively), compared to CS hydrogels and PEG-based swelling controls, indicating that desulfation may actually enhance the response of MSCs to soluble chondrogenic cues, such as TGF-β1. Thus, desulfated chondroitin materials present a promising biomaterial tool to further investigate electrostatic GAG/growth factor interactions, especially for repair of cartilaginous tissues. Copyright © 2013 Elsevier Ltd. All rights reserved.

On the Proper Calculation of Electrostatic Interactions in Solid-Supported Bilayer Systems

DTIC Science & Technology

2011-01-01

the effects of im- plementing different electrostatic boundary conditions on the structural and electrostatic properties of a quartz/water/vacuum...interface and a similar quartz-supported hydrated lipid bilayer exposed to vacuum. Since these interfacial systems have a net polarization, implementing the...implemented electrostatic boundary condition removed these inconsistencies. This formulation is generally applicable to similar interfacial systems in bulk

On the role of electrostatics in protein-protein interactions

NASA Astrophysics Data System (ADS)

Zhang, Zhe; Witham, Shawn; Alexov, Emil

2011-06-01

The role of electrostatics in protein-protein interactions and binding is reviewed in this paper. A brief outline of the computational modeling, in the framework of continuum electrostatics, is presented and the basic electrostatic effects occurring upon the formation of the complex are discussed. The effect of the salt concentration and pH of the water phase on protein-protein binding free energy is demonstrated which indicates that the increase of the salt concentration tends to weaken the binding, an observation that is attributed to the optimization of the charge-charge interactions across the interface. It is pointed out that the pH-optimum (pH of optimal binding affinity) varies among the protein-protein complexes, and perhaps is a result of their adaptation to particular subcellular compartments. The similarities and differences between hetero- and homo-complexes are outlined and discussed with respect to the binding mode and charge complementarity.

On the role of electrostatics on protein-protein interactions

PubMed Central

Zhang, Zhe; Witham, Shawn; Alexov, Emil

2011-01-01

The role of electrostatics on protein-protein interactions and binding is reviewed in this article. A brief outline of the computational modeling, in the framework of continuum electrostatics, is presented and basic electrostatic effects occurring upon the formation of the complex are discussed. The role of the salt concentration and pH of the water phase on protein-protein binding free energy is demonstrated and indicates that the increase of the salt concentration tends to weaken the binding, an observation that is attributed to the optimization of the charge-charge interactions across the interface. It is pointed out that the pH-optimum (pH of optimal binding affinity) varies among the protein-protein complexes, and perhaps is a result of their adaptation to particular subcellular compartment. At the end, the similarities and differences between hetero- and homo-complexes are outlined and discussed with respect to the binding mode and charge complementarity. PMID:21572182

Interaction between stray electrostatic fields and a charged free-falling test mass.

PubMed

Antonucci, F; Cavalleri, A; Dolesi, R; Hueller, M; Nicolodi, D; Tu, H B; Vitale, S; Weber, W J

2012-05-04

We present an experimental analysis of force noise caused by stray electrostatic fields acting on a charged test mass inside a conducting enclosure, a key problem for precise gravitational experiments. Measurement of the average field that couples to the test mass charge, and its fluctuations, is performed with two independent torsion pendulum techniques, including direct measurement of the forces caused by a change in electrostatic charge. We analyze the problem with an improved electrostatic model that, coupled with the experimental data, also indicates how to correctly measure and null the stray field that interacts with the test mass charge. Our measurements allow a conservative upper limit on acceleration noise, of 2  (fm/s2)/Hz(1/2) for frequencies above 0.1 mHz, for the interaction between stray fields and charge in the LISA gravitational wave mission.

A First-Principles Approach to the Dynamics and Electronic Properties of p-Nitroaniline in Water.

PubMed

Cabral, Benedito J Costa; Coutinho, Kaline; Canuto, Sylvio

2016-06-09

Born-Oppenheimer molecular dynamics of p-nitroaniline (PNA) in water was carried out and the electronic structure was investigated by time-dependent density functional theory. Hydrogen bonding involving the PNA nitro and amine groups and the water molecules leads to an ∼160 cm(-1) red shift of the ν(N-O) and ν(N-H) stretching frequencies relative to the gas phase species. Our estimate for the peak position of the charge transfer (CT) band in the absorption spectrum of PNA in water (∼3.5 eV) is in good agreement with experimental data (3.3 eV). We have investigated the specific role played by local hydrogen bonding and electrostatic interactions on the electronic absorption spectrum. It is shown that although electrostatic interactions play a major role for explaining the structure of the PNA CT band in water, the theoretical prediction of the observed red shift is improved by the explicit consideration of local hydrogen bonding of PNA to water. For isolated PNA, we predict that the dipole moment of the second excited state (S2) is 9.6 D greater than ground state (S0) dipole, which is in good agreement with experimental information (8.2-9.3 D). Calculation of charge transfer indexes for the two first excitations of PNA in water indicates that despite the feature that a small fraction of S1 states (<5%) may exhibit some CT character, CT states in solution are mainly associated with S2 ← S0 transitions.

Electrostatic networks control plug stabilization in the PapC usher.

PubMed

Pham, Thieng; Henderson, Nadine S; Werneburg, Glenn T; Thanassi, David G; Delcour, Anne H

2015-01-01

The PapC usher, a β-barrel pore in the outer membrane of uropathogenic Escherichia coli, is used for assembly of the P pilus, a key virulence factor in bacterial colonization of human kidney cells. Each PapC protein is composed of a 24-stranded β-barrel channel, flanked by N- and C-terminal globular domains protruding into the periplasm, and occluded by a plug domain (PD). The PD is displaced from the channel towards the periplasm during pilus biogenesis, but the molecular mechanism for PD displacement remains unclear. Two structural features within the β-barrel, an α-helix and β5-6 hairpin loop, may play roles in controlling plug stabilization. Here we have tested clusters of residues at the interface of the plug, barrel, α-helix and hairpin, which participate in electrostatic networks. To assess the roles of these residues in plug stabilization, we used patch-clamp electrophysiology to compare the activity of wild-type and mutant PapC channels containing alanine substitutions at these sites. Mutations interrupting each of two salt bridge networks were relatively ineffective in disrupting plug stabilization. However, mutation of two pairs of arginines located at the inner and the outer surfaces of the PD resulted in an enhanced propensity for plug displacement. One arginine pair involved in a repulsive interaction between the linkers that tether the plug to the β-barrel was particularly sensitive to mutation. These results suggest that plug displacement, which is necessary for pilus assembly and translocation, may require a weakening of key electrostatic interactions between the plug linkers, and the plug and the α-helix.

Subunit assembly of hemoglobin: an important determinant of hematologic phenotype.

PubMed

Bunn, H F

1987-01-01

Hemoglobin's physiologic properties depend on the orderly assembly of its subunits in erythropoietic cells. The biosynthesis of alpha- and beta-globin polypeptide chains is normally balanced. Heme rapidly binds to the globin subunit, either during translation or shortly thereafter. The formation of the alpha beta-dimer is facilitated by electrostatic attraction of a positively charged alpha-subunit to a negatively charged beta-subunit. The alpha beta-dimer dissociates extremely slowly. The difference between the rate of dissociation of alpha beta- and alpha gamma-dimers with increasing pH explains the well-known alkaline resistance of Hb F. Two dimers combine to form the functioning alpha 2 beta 2-tetramer. This model of hemoglobin assembly explains the different levels of positively charged and negatively charged mutant hemoglobins that are encountered in heterozygotes and the effect of alpha-thalassemia and heme deficiency states in modifying the level of the variant hemoglobin as well as Hb A2. Electrostatic interactions also affect the binding of hemoglobin to the cytoplasmic surface of the red cell membrane and may underlie the formation of target cells. Enhanced binding of positively charged variants such as S and C trigger a normally dormant pathway for potassium and water loss. Thus, the positive charge on beta c is responsible for the two major contributors to the pathogenesis of Hb SC disease: increased proportion of Hb S and increased intracellular hemoglobin concentration. It is likely that electrostatic interactions play an important role in the assembly of a number of other multisubunit macromolecules, including membrane receptors, cytoskeletal proteins, and DNA binding proteins.

Emphasizing the Significance of Electrostatic Interactions in Chemical Bonding

ERIC Educational Resources Information Center

Venkataraman, Bhawani

2017-01-01

This paper describes a pedagogical approach to help students understand chemical bonding by emphasizing the importance of electrostatic interactions between atoms. The approach draws on prior studies that have indicated many misconceptions among students in understanding the nature of the chemical bond and energetics associated with bond formation…

PBEQ-Solver for online visualization of electrostatic potential of biomolecules.

PubMed

Jo, Sunhwan; Vargyas, Miklos; Vasko-Szedlar, Judit; Roux, Benoît; Im, Wonpil

2008-07-01

PBEQ-Solver provides a web-based graphical user interface to read biomolecular structures, solve the Poisson-Boltzmann (PB) equations and interactively visualize the electrostatic potential. PBEQ-Solver calculates (i) electrostatic potential and solvation free energy, (ii) protein-protein (DNA or RNA) electrostatic interaction energy and (iii) pKa of a selected titratable residue. All the calculations can be performed in both aqueous solvent and membrane environments (with a cylindrical pore in the case of membrane). PBEQ-Solver uses the PBEQ module in the biomolecular simulation program CHARMM to solve the finite-difference PB equation of molecules specified by users. Users can interactively inspect the calculated electrostatic potential on the solvent-accessible surface as well as iso-electrostatic potential contours using a novel online visualization tool based on MarvinSpace molecular visualization software, a Java applet integrated within CHARMM-GUI (http://www.charmm-gui.org). To reduce the computational time on the server, and to increase the efficiency in visualization, all the PB calculations are performed with coarse grid spacing (1.5 A before and 1 A after focusing). PBEQ-Solver suggests various physical parameters for PB calculations and users can modify them if necessary. PBEQ-Solver is available at http://www.charmm-gui.org/input/pbeqsolver.

Osmotic Pressure of Aqueous Chondroitin Sulfate Solution: A Molecular Modeling Investigation

PubMed Central

Bathe, Mark; Rutledge, Gregory C.; Grodzinsky, Alan J.; Tidor, Bruce

2005-01-01

The osmotic pressure of chondroitin sulfate (CS) solution in contact with an aqueous 1:1 salt reservoir of fixed ionic strength is studied using a recently developed coarse-grained molecular model. The effects of sulfation type (4- vs. 6-sulfation), sulfation pattern (statistical distribution of sulfate groups along a chain), ionic strength, CS intrinsic stiffness, and steric interactions on CS osmotic pressure are investigated. At physiological ionic strength (0.15 M NaCl), the sulfation type and pattern, as measured by a standard statistical description of copolymerization, are found to have a negligible influence on CS osmotic pressure, which depends principally on the mean volumetric fixed charge density. The intrinsic backbone stiffness characteristic of polysaccharides such as CS, however, is demonstrated to contribute significantly to its osmotic pressure behavior, which is similar to that of a solution of charged rods for the 20-disaccharide chains considered. Steric excluded volume is found to play a negligible role in determining CS osmotic pressure at physiological ionic strength due to the dominance of repulsive intermolecular electrostatic interactions that maintain chains maximally spaced in that regime, whereas at high ionic-strength steric interactions become dominant due to electrostatic screening. Osmotic pressure predictions are compared to experimental data and to well-established theoretical models including the Donnan theory and the Poisson-Boltzmann cylindrical cell model. PMID:16055525

Molecular Basis for Phosphorylation-dependent SUMO Recognition by the DNA Repair Protein RAP80.

PubMed

Anamika; Spyracopoulos, Leo

2016-02-26

Recognition and repair of double-stranded DNA breaks (DSB) involves the targeted recruitment of BRCA tumor suppressors to damage foci through binding of both ubiquitin (Ub) and the Ub-like modifier SUMO. RAP80 is a component of the BRCA1 A complex, and plays a key role in the recruitment process through the binding of Lys(63)-linked poly-Ub chains by tandem Ub interacting motifs (UIM). RAP80 also contains a SUMO interacting motif (SIM) just upstream of the tandem UIMs that has been shown to specifically bind the SUMO-2 isoform. The RAP80 tandem UIMs and SIM function collectively for optimal recruitment of BRCA1 to DSBs, although the molecular basis of this process is not well understood. Using NMR spectroscopy, we demonstrate that the RAP80 SIM binds SUMO-2, and that both specificity and affinity are enhanced through phosphorylation of the canonical CK2 site within the SIM. The affinity increase results from an enhancement of electrostatic interactions between the phosphoserines of RAP80 and the SIM recognition module within SUMO-2. The NMR structure of the SUMO-2·phospho-RAP80 complex reveals that the molecular basis for SUMO-2 specificity is due to isoform-specific sequence differences in electrostatic SIM recognition modules. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Insights into the Membrane Interactions of the Saposin-Like Proteins Na-SLP-1 and Ac-SLP-1 from Human and Dog Hookworm

PubMed Central

Willis, Charlene; Wang, Conan K.; Osman, Asiah; Simon, Anne; Pickering, Darren; Mulvenna, Jason; Riboldi-Tunicliffe, Alan; Jones, Malcolm K.; Loukas, Alex; Hofmann, Andreas

2011-01-01

Saposin-like proteins (SAPLIPs) from soil-transmitted helminths play pivotal roles in host-pathogen interactions and have a high potential as targets for vaccination against parasitic diseases. We have identified two non-orthologous SAPLIPs from human and dog hookworm, Na-SLP-1 and Ac-SLP-1, and solved their three-dimensional crystal structures. Both proteins share the property of membrane binding as monitored by liposome co-pelleting assays and monolayer adsorption. Neither SAPLIP displayed any significant haemolytic or bactericidal activity. Based on the structural information, as well as the results from monolayer adsorption, we propose models of membrane interactions for both SAPLIPs. Initial membrane contact of the monomeric Na-SLP-1 is most likely by electrostatic interactions between the membrane surface and a prominent basic surface patch. In case of the dimeric Ac-SLP-1, membrane interactions are most likely initiated by a unique tryptophan residue that has previously been implicated in membrane interactions in other SAPLIPs. PMID:21991310

Insights into the membrane interactions of the saposin-like proteins Na-SLP-1 and Ac-SLP-1 from human and dog hookworm.

PubMed

Willis, Charlene; Wang, Conan K; Osman, Asiah; Simon, Anne; Pickering, Darren; Mulvenna, Jason; Riboldi-Tunicliffe, Alan; Jones, Malcolm K; Loukas, Alex; Hofmann, Andreas

2011-01-01

Saposin-like proteins (SAPLIPs) from soil-transmitted helminths play pivotal roles in host-pathogen interactions and have a high potential as targets for vaccination against parasitic diseases. We have identified two non-orthologous SAPLIPs from human and dog hookworm, Na-SLP-1 and Ac-SLP-1, and solved their three-dimensional crystal structures. Both proteins share the property of membrane binding as monitored by liposome co-pelleting assays and monolayer adsorption. Neither SAPLIP displayed any significant haemolytic or bactericidal activity. Based on the structural information, as well as the results from monolayer adsorption, we propose models of membrane interactions for both SAPLIPs. Initial membrane contact of the monomeric Na-SLP-1 is most likely by electrostatic interactions between the membrane surface and a prominent basic surface patch. In case of the dimeric Ac-SLP-1, membrane interactions are most likely initiated by a unique tryptophan residue that has previously been implicated in membrane interactions in other SAPLIPs.

Probe diffusion of labeled polymers inside polyacrylic acid solutions: A polyelectrolyte effect

NASA Astrophysics Data System (ADS)

Mishra, Banani; Mithra, K.; Khandai, Santripti; Jena, Sidhartha S.

2018-05-01

Probe diffusion of fluorescently labeled Dextran 40 inside polyelectrolyte solution of polyacrylic acid (PAA) was investigated using Fluorescence Recovery After Photobleaching technique. The crowding and interaction effects on probe diffusion were controlled by tuning background polymer and added external electrolyte concentration. For all the salt concentration, an overall decrease in diffusion coefficient is observed with rise in polymer concentration. The diffusion coefficient decreases with decrease in salt concentration whereas the solution viscosity increases, indicating a competition between viscous drag and electrostatic interaction. A large positive deviation from the ideal Stokes-Einstein relation is observed for high polymer and low salt concentration, which reduces markedly with addition of salt confirming polyelectrolyte effects, plays a major role in deciding the probe diffusion.

Schottky barrier at graphene/metal oxide interfaces: insight from first-principles calculations

NASA Astrophysics Data System (ADS)

Cheng, Kai; Han, Nannan; Su, Yan; Zhang, Junfeng; Zhao, Jijun

2017-02-01

Anode materials play an important role in determining the performance of lithium ion batteries. In experiment, graphene (GR)/metal oxide (MO) composites possess excellent electrochemical properties and are promising anode materials. Here we perform density functional theory calculations to explore the interfacial interaction between GR and MO. Our result reveals generally weak physical interactions between GR and several MOs (including Cu2O, NiO). The Schottky barrier height (SBH) in these metal/semiconductor heterostructures are computed using the macroscopically averaged electrostatic potential method, and the role of interfacial dipole is discussed. The calculated SBHs below 1 eV suggest low contact resistance; thus these GR/MO composites are favorable anode materials for better lithium ion batteries.

Schottky barrier at graphene/metal oxide interfaces: insight from first-principles calculations.

PubMed

Cheng, Kai; Han, Nannan; Su, Yan; Zhang, Junfeng; Zhao, Jijun

2017-02-06

Anode materials play an important role in determining the performance of lithium ion batteries. In experiment, graphene (GR)/metal oxide (MO) composites possess excellent electrochemical properties and are promising anode materials. Here we perform density functional theory calculations to explore the interfacial interaction between GR and MO. Our result reveals generally weak physical interactions between GR and several MOs (including Cu2O, NiO). The Schottky barrier height (SBH) in these metal/semiconductor heterostructures are computed using the macroscopically averaged electrostatic potential method, and the role of interfacial dipole is discussed. The calculated SBHs below 1 eV suggest low contact resistance; thus these GR/MO composites are favorable anode materials for better lithium ion batteries.

Positive Charges on the Surface of Thaumatin Are Crucial for the Multi-Point Interaction with the Sweet Receptor.

PubMed

Masuda, Tetsuya; Kigo, Satomi; Mitsumoto, Mayuko; Ohta, Keisuke; Suzuki, Mamoru; Mikami, Bunzo; Kitabatake, Naofumi; Tani, Fumito

2018-01-01

Thaumatin, an intensely sweet-tasting protein, elicits sweet taste with a threshold of only 50 nM. Previous studies from our laboratory suggested that the complex model between the T1R2-T1R3 sweet receptor and thaumatin depends critically on the complementarity of electrostatic potentials. In order to further validate this model, we focused on three lysine residues (Lys78, Lys106, and Lys137), which were expected to be part of the interaction sites. Three thaumatin mutants (K78A, K106A, and K137A) were prepared and their threshold values of sweetness were examined. The results showed that the sweetness of K106A was reduced by about three times and those of K78A and K137A were reduced by about five times when compared to wild-type thaumatin. The three-dimensional structures of these mutants were also determined by X-ray crystallographic analyses at atomic resolutions. The overall structures of mutant proteins were similar to that of wild-type but the electrostatic potentials around the mutated sites became more negative. Since the three lysine residues are located in 20-40 Å apart each other on the surface of thaumatin molecule, these results suggest the positive charges on the surface of thaumatin play a crucial role in the interaction with the sweet receptor, and are consistent with a large surface is required for interaction with the sweet receptor, as proposed by the multipoint interaction model named wedge model.

Prospective Teachers' Difficulties in Interpreting Elementary Phenomena of Electrostatic Interactions: Indicators of the Status of Their Intuitive Ideas

ERIC Educational Resources Information Center

Criado, Ana Maria; Garcia-Carmona, Antonio

2010-01-01

Student teachers were tested before and after a teaching unit on electrostatic interactions in an attempt to consider their intuitive ideas and concept development. A study was made of students' explanations of basic interactions: those between two charged bodies, and those between a charged body and a neutral body. Two indicators of the cognitive…

Course 1: Physics of Protein-DNA Interaction

NASA Astrophysics Data System (ADS)

Bruinsma, R. F.

1 Introduction 1.1 The central dogma and bacterial gene expression 1.2 Molecular structure 2 Thermodynamics and kinetics of repressor-DNA interaction 2.1 Thermodynamics and the lac repressor 2.2 Kinetics of repressor-DNA interaction 3 DNA deformability and protein-DNA interaction 3.1 Introduction 3.2 The worm-like chain 3.3 The RST model 4 Electrostatics in water and protein-DNA interaction 4.1 Macro-ions and aqueous electrostatics 4.2 The primitive model 4.3 Manning condensation 4.4 Counter-ion release and non-specific protein-DNA interaction

Role of the Cationic C-Terminal Segment of Melittin on Membrane Fragmentation.

PubMed

Therrien, Alexandre; Fournier, Alain; Lafleur, Michel

2016-05-05

The widespread distribution of cationic antimicrobial peptides capable of membrane fragmentation in nature underlines their importance to living organisms. In the present work, we determined the impact of the electrostatic interactions associated with the cationic C-terminal segment of melittin, a 26-amino acid peptide from bee venom (net charge +6), on its binding to model membranes and on the resulting fragmentation. In order to detail the role played by the C-terminal charges, we prepared a melittin analogue for which the four cationic amino acids in positions 21-24 were substituted with the polar residue citrulline, providing a peptide with the same length and amphiphilicity but with a lower net charge (+2). We compared the peptide bilayer affinity and the membrane fragmentation for bilayers prepared from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/1,2-dipalmitoyl-sn-glycero-3-phospho-l-serine (DPPS) mixtures. It is shown that neutralization of the C-terminal considerably increased melittin affinity for zwitterionic membranes. The unfavorable contribution associated with transferring the cationic C-terminal in a less polar environment was reduced, leaving the hydrophobic interactions, which drive the peptide insertion in bilayers, with limited counterbalancing interactions. The presence of negatively charged lipids (DPPS) in bilayers increased melittin binding by introducing attractive electrostatic interactions, the augmentation being, as expected, greater for native melittin than for its citrullinated analogue. The membrane fragmentation power of the peptide was shown to be controlled by electrostatic interactions and could be modulated by the charge carried by both the membrane and the lytic peptide. The analysis of the lipid composition of the extracted fragments from DPPC/DPPS bilayers revealed no lipid specificity. It is proposed that extended phase separations are more susceptible to lead to the extraction of a lipid species in a specific manner than a specific lipid-peptide affinity. The present work on the lipid extraction by melittin and citrullinated melittin with model membranes emphasizes the complex relation between the affinity, the lipid extraction/membrane fragmentation, and the lipid specificity.

A Role for Weak Electrostatic Interactions in Peripheral Membrane Protein Binding

PubMed Central

Khan, Hanif M.; He, Tao; Fuglebakk, Edvin; Grauffel, Cédric; Yang, Boqian; Roberts, Mary F.; Gershenson, Anne; Reuter, Nathalie

2016-01-01

Bacillus thuringiensis phosphatidylinositol-specific phospholipase C (BtPI-PLC) is a secreted virulence factor that binds specifically to phosphatidylcholine (PC) bilayers containing negatively charged phospholipids. BtPI-PLC carries a negative net charge and its interfacial binding site has no obvious cluster of basic residues. Continuum electrostatic calculations show that, as expected, nonspecific electrostatic interactions between BtPI-PLC and membranes vary as a function of the fraction of anionic lipids present in the bilayers. Yet they are strikingly weak, with a calculated ΔGel below 1 kcal/mol, largely due to a single lysine (K44). When K44 is mutated to alanine, the equilibrium dissociation constant for small unilamellar vesicles increases more than 50 times (∼2.4 kcal/mol), suggesting that interactions between K44 and lipids are not merely electrostatic. Comparisons of molecular-dynamics simulations performed using different lipid compositions reveal that the bilayer composition does not affect either hydrogen bonds or hydrophobic contacts between the protein interfacial binding site and bilayers. However, the occupancies of cation-π interactions between PC choline headgroups and protein tyrosines vary as a function of PC content. The overall contribution of basic residues to binding affinity is also context dependent and cannot be approximated by a rule-of-thumb value because these residues can contribute to both nonspecific electrostatic and short-range protein-lipid interactions. Additionally, statistics on the distribution of basic amino acids in a data set of membrane-binding domains reveal that weak electrostatics, as observed for BtPI-PLC, might be a less unusual mechanism for peripheral membrane binding than is generally thought. PMID:27028646

An expanded genetic code for probing the role of electrostatics in enzyme catalysis by vibrational Stark spectroscopy.

PubMed

Völler, Jan-Stefan; Biava, Hernan; Hildebrandt, Peter; Budisa, Nediljko

2017-11-01

To find experimental validation for electrostatic interactions essential for catalytic reactions represents a challenge due to practical limitations in assessing electric fields within protein structures. This review examines the applications of non-canonical amino acids (ncAAs) as genetically encoded probes for studying the role of electrostatic interactions in enzyme catalysis. ncAAs constitute sensitive spectroscopic probes to detect local electric fields by exploiting the vibrational Stark effect (VSE) and thus have the potential to map the protein electrostatics. Mapping the electrostatics in proteins will improve our understanding of natural catalytic processes and, in beyond, will be helpful for biocatalyst engineering. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier B.V. All rights reserved.

Long Range Debye-Hückel Correction for Computation of Grid-based Electrostatic Forces Between Biomacromolecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mereghetti, Paolo; Martinez, M.; Wade, Rebecca C.

Brownian dynamics (BD) simulations can be used to study very large molecular systems, such as models of the intracellular environment, using atomic-detail structures. Such simulations require strategies to contain the computational costs, especially for the computation of interaction forces and energies. A common approach is to compute interaction forces between macromolecules by precomputing their interaction potentials on three-dimensional discretized grids. For long-range interactions, such as electrostatics, grid-based methods are subject to finite size errors. We describe here the implementation of a Debye-Hückel correction to the grid-based electrostatic potential used in the SDA BD simulation software that was applied to simulatemore » solutions of bovine serum albumin and of hen egg white lysozyme.« less

Structure evolution of gelatin particles induced by pH and ionic strength.

PubMed

Xu, Jing; Li, Tianduo; Tao, Furong; Cui, Yuezhi; Xia, Yongmei

2013-03-01

Microstructure of gelatin particles played a key role in determining the physicochemical properties of gelatin. Ionic strength and pH as systematic manners were considered to affect gelatin particles structure on the micrometer scale. Scanning electron microscopy was used for depicting the morphologies of gelatin particles. Increasing pH to 10.0 or decreasing pH to 4.0, spherical, spindle, and irregular aggregates of gelatin particles at 2, 6, 10, and 14% solution (w/w) were all transformed to spindle aggregates. When NaCl was added to the system, the molecular chains of gelatin possibly rearranged themselves in a stretched state, and the ribbon aggregates was observed. The structural transitions of gelatin aggregates were strongly depended on the electrostatic repulsion. In the gelatin-sodium dodecyl sulfate (SDS) case, the micrometer scale of aggregates was larger and the different degrees of cross-links were induced through hydrophobic interaction and electrostatic repulsion. Copyright © 2012 Wiley Periodicals, Inc.

Role of electrostatic interactions during protein ultrafiltration.

PubMed

Rohani, Mahsa M; Zydney, Andrew L

2010-10-15

A number of studies over the last decade have clearly demonstrated the importance of electrostatic interactions on the transport of charged proteins through semipermeable ultrafiltration membranes. This paper provides a review of recent developments in this field with a focus on the role of both protein and membrane charge on the rate of protein transport. Experimental results are analyzed using available theoretical models developed from the solution of the Poisson-Boltzmann equation for the partitioning of a charged particle into a charged pore. The potential of exploiting these electrostatic interactions for selective protein separations and for the development of ultrafiltration membranes with enhanced performance characteristics is also examined. Copyright © 2010 Elsevier B.V. All rights reserved.

Contribution of Electrostatics to the Kinetics of Electron Transfer from NADH-Cytochrome b5 Reductase to Fe(III)-Cytochrome b5.

PubMed

Kollipara, Sireesha; Tatireddy, Shivakishore; Pathirathne, Thusitha; Rathnayake, Lasantha K; Northrup, Scott H

2016-08-25

Brownian dynamics (BD) simulations provide here a theoretical atomic-level treatment of the reduction of human ferric cytochrome b5 (cyt b5) by NADH-cytochrome b5 reductaste (cyt b5r) and several of its mutants. BD is used to calculate the second-order rate constant of electron transfer (ET) between the proteins for direct correlation with experiments. Interestingly, the inclusion of electrostatic forces dramatically increases the reaction rate of the native proteins despite the overall negative charge of both proteins. The role played by electrostatic charge distribution in stabilizing the ET complexes and the role of mutations of several amino acid residues in stabilizing or destabilizing the complexes are analyzed. The complex with the shortest ET reaction distance (d = 6.58 Å) from rigid body BD is further subjected to 1 ns of molecular dynamics (MD) in a periodic box of TIP3P water to produce a more stable complex allowed by flexibility and with a shorter average reaction distance d = 6.02 Å. We predict a docking model in which the following ion-ion interactions are dominant (cyt b5r/cyt b5): Lys162-Heme O1D/Lys163-Asp64/Arg91-Heme O1A/Lys125-Asp70.

Swelling of biological and semiflexible polyelectrolytes.

PubMed

Dobrynin, Andrey V; Carrillo, Jan-Michael Y

2009-10-21

We have developed a theoretical model of swelling of semiflexible (biological) polyelectrolytes in salt solutions. Our approach is based on separation of length scales which allowed us to split a chain's electrostatic energy into two parts that describe local and remote electrostatic interactions along the polymer backbone. The local part takes into account interactions between charged monomers that are separated by distances along the polymer backbone shorter than the chain's persistence length. These electrostatic interactions renormalize chain persistence length. The second part includes electrostatic interactions between remote charged pairs along the polymer backbone located at distances larger than the chain persistence length. These interactions are responsible for chain swelling. In the framework of this approach we calculated effective chain persistence length and chain size as a function of the Debye screening length, chain degree of ionization, bare persistence length and chain degree of polymerization. Our crossover expression for the effective chain's persistence length is in good quantitative agreement with the experimental data on DNA. We have been able to fit experimental datasets by using two adjustable parameters: DNA ionization degree (α = 0.15-0.17) and a bare persistence length (l(p) = 40-44 nm).

Electrostatic complementarity between proteins and ligands. 1. Charge disposition, dielectric and interface effects

NASA Astrophysics Data System (ADS)

Chau, P.-L.; Dean, P. M.

1994-10-01

Electrostatic interactions have always been considered an important factor governing ligand-receptor interactions. Previous work in this field has established the existence of electrostatic complementarity between the ligand and its receptor site. However, this property has not been treated rigorously, and the description remains largely qualitative. In this work, 34 data sets of high quality were chosen from the Brookhaven Protein Databank. The electrostatic complementarity has been calculated between the surface potentials; complementarity is absent between adjacent or neighbouring atoms of the ligand and the receptor. There is little difference between complementarities on the total ligand surface and the interfacial region. Altering the homogeneous dielectric to distance-dependent dielectrics reduces the complementarity slightly, but does not affect the pattern of complementarity.

Electrostatic complementarity between proteins and ligands. 1. Charge disposition, dielectric and interface effects.

PubMed

Chau, P L; Dean, P M

1994-10-01

Electrostatic interactions have always been considered an important factor governing ligand-receptor interactions. Previous work in this field has established the existence of electrostatic complementarity between the ligand and its receptor site. However, this property has not been treated rigorously, and the description remains largely qualitative. In this work, 34 data sets of high quality were chosen from the Brookhaven Protein Databank. The electrostatic complementary has been calculated between the surface potentials; complementarity is absent between adjacent or neighbouring atoms of the ligand and the receptor. There is little difference between complementarities on the total ligand surface and the interfacial region. Altering the homogeneous dielectric to distance-dependent dielectrics reduces the complementarity slightly, but does not affect the pattern of complementarity.

Protonmotive force: development of electrostatic drivers for synthetic molecular motors.

PubMed

Crowley, James D; Steele, Ian M; Bosnich, Brice

2006-12-04

Ferrocene has been investigated as a platform for developing protonmotive electrostatic drivers for molecular motors. When two 3-pyridine groups are substituted to the (rapidly rotating) cyclopentadienyl (Cp) rings of ferrocene, one on each Cp, it is shown that the (Cp) eclipsed, pi-stacked rotameric conformation is preferred both in solution and in the solid state. Upon quaternization of both of the pyridines substituents, either by protonation or by alkylation, it is shown that the preferred rotameric conformation is one where the pyridinium groups are rotated away from the fully pi-stacked conformation. Electrostatic calculations indicate that the rotation is caused by the electrostatic repulsion between the charges. Consistently, when the pi-stacking energy is increased pi-stacked population increases, and conversely when the electrostatic repulsion is increased pi-stacked population is decreased. This work serves to provide an approximate estimate of the amount of torque that the electrostatically driven ferrocene platform can generate when incorporated into a molecular motor. The overall conclusion is that the electrostatic interaction energy between dicationic ferrocene dipyridyl systems is similar to the pi-stacking interaction energy and, consequently, at least tricationic systems are required to fully uncouple the pi-stacked pyridine substituents.

Material Science Smart Coatings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rubinstein, A. I.; Sabirianov, R. F.; Namavar, Fereydoon

2014-07-01

The contribution of electrostatic interactions to the free energy of binding between model protein and a ceramic implant surface in the aqueous solvent, considered in the framework of the nonlocal electrostatic model, is calculated as a function of the implant low-frequency dielectric constant. We show that the existence of a dynamically ordered (low-dielectric) interfacial solvent layer at the protein-solvent and ceramic-solvent interface markedly increases charging energy of the protein and ceramic implant, and consequently makes the electrostatic contribution to the protein-ceramic binding energy more favorable (attractive). Our analysis shows that the corresponding electrostatic energy between protein and oxide ceramics dependsmore » nonmonotonically on the dielectric constant of ceramic, ε C. Obtained results indicate that protein can attract electrostatically to the surface if ceramic material has a moderate ε C below or about 35 (in particularly ZrO 2 or Ta 2O 5). This is in contrast to classical (local) consideration of the solvent, which demonstrates an unfavorable electrostatic interaction of protein with typical metal oxide ceramic materials (ε C>10). Thus, a solid implant coated by combining oxide ceramic with a reduced dielectric constant can be beneficial to strengthen the electrostatic binding of the protein-implant complex.« less

Passive membrane penetration by ZnO nanoparticles is driven by the interplay of electrostatic and phase boundary conditions.

PubMed

Tiwari, Anuj; Prince, Ashutosh; Arakha, Manoranjan; Jha, Suman; Saleem, Mohammed

2018-02-15

The internalization of nanoparticles through the biological membrane is of immense importance for biomedical applications. A fundamental understanding of the lipid specificity and the role of the membrane biochemical and physical forces at play in modulating penetration are lacking. The current understanding of nanoparticle-membrane interaction is drawn mostly from computational studies and lacks sufficient experimental evidence. Herein, using confocal fluorescence imaging and potentiometric dye-based fluorimetry, we first investigated the interaction of ZnONP in both multi-component and individual lipid membranes using cell-like giant unilamellar vesicles to dissect the lipid specificity; also, we investigated the changes in membrane order, anisotropy and hydrophobicity. ZnONP was found to interact with phosphatidylinositol and phosphatidylcholine head-group-containing lipids specifically. We further investigated the interaction of ZnONP with three physiologically relevant membrane conditions varying in composition and dipole potential. We found that ZnONP interaction leads to a photoinduced enhancement of the partial-to-complete phase separation depending upon the membrane composition and cholesterol content. Interestingly, while the lipid order of a partially-phase-separated membrane remained unchanged upon ZnONP crowding, a fully-phase-separated membrane showed an increase in the lipid order. Strikingly, ZnONP crowding induced a contrasting effect on the fluorescence anisotropy of the membrane upon binding to the two membrane conditions, in line with the measured diffusion coefficient. ZnONP seems to preferentially penetrate through the liquid disordered areas of the membrane and the boundaries of the phase-separated regions driven by the interplay between the electrostatics and phase boundary conditions, which are collectively dictated by the composition and ZnONP-induced lipid reorganization. The results may lead to a greater understanding of the interplay of membrane parameters and ZnONP interaction in driving passive penetration.

Kinetic recognition of the retinoblastoma tumor suppressor by a specific protein target.

PubMed

Chemes, Lucía B; Sánchez, Ignacio E; de Prat-Gay, Gonzalo

2011-09-16

The retinoblastoma tumor suppressor (Rb) plays a key role in cell cycle control and is linked to various types of human cancer. Rb binds to the LxCxE motif, present in a number of cellular and viral proteins such as AdE1A, SV40 large T-antigen and human papillomavirus (HPV) E7, all instrumental in revealing fundamental mechanisms of tumor suppression, cell cycle control and gene expression. A detailed kinetic study of RbAB binding to the HPV E7 oncoprotein shows that an LxCxE-containing E7 fragment binds through a fast two-state reaction strongly favored by electrostatic interactions. Conversely, full-length E7 binds through a multistep process involving a pre-equilibrium between E7 conformers, a fast electrostatically driven association step guided by the LxCxE motif and a slow conformational rearrangement. This kinetic complexity arises from the conformational plasticity and intrinsically disordered nature of E7 and from multiple interaction surfaces present in both proteins. Affinity differences between E7N domains from high- and low-risk types are explained by their dissociation rates. In fact, since Rb is at the center of a large protein interaction network, fast and tight recognition provides an advantage for disruption by the viral proteins, where the balance of physiological and pathological interactions is dictated by kinetic ligand competition. The localization of the LxCxE motif within an intrinsically disordered domain provides the fast, diffusion-controlled interaction that allows viral proteins to outcompete physiological targets. We describe the interaction mechanism of Rb with a protein ligand, at the same time an LxCxE-containing model target, and a paradigmatic intrinsically disordered viral oncoprotein. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structural investigation on the adsorption of the MARCKS peptide on anionic lipid monolayers - effects beyond electrostatic.

PubMed

Dietrich, Undine; Krüger, Peter; Käs, Josef A

2011-05-01

The presence of charged lipids in the cell membrane constitutes the background for the interaction with numerous membrane proteins. As a result, the valence of the lipids plays an important role concerning their lateral organization in the membrane and therefore the very manner of this interaction. This present study examines this aspect, particularly regarding to the interaction of the anionic lipid DPPS with the highly basic charged effector domain of the MARCKS protein, examined in monolayer model systems. Film balance, fluorescence microscopy and X-ray reflection/diffraction measurements were used to study the behavior of DPPS in a mixture with DPPC for its dependance on the presence of MARCKS (151-175). In the mixed monolayer, both lipids are completely miscible therefore DPPS is incorporated in the ordered crystalline DPPC domains as well. The interaction of MARCKS peptide with the mixed monolayer leads to the formation of lipid/peptide clusters causing an elongation of the serine group of the DPPS up to 7Å in direction to surface normal into the subphase. The large cationic charge of the peptide pulls out the serine group of the interface which simultaneously causes an elongation of the phosphodiester group of the lipid fraction too. The obtained results were used to compare the interaction of MARCKS peptide with the polyvalent PIP(2) in mixed monolayers. On this way we surprisingly find out, that the relative small charge difference of the anionic lipids causes a significant different interaction with MARCKS (151-175). The lateral arrangement of the anionic lipids depends on their charge values and determines the diffusion of the electrostatic binding clusters within the membrane. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

A Printing-Centric Approach to the Electrostatic Modification of Polymer/Clay Composites for use in 3D Direct-Ink Writing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rauzan, Brittany; Lehman, Sean; McCracken, Josell

Polymer/clay composite inks are exceptionally useful materials for fabrication processes based on 3D direct-ink writing, however, there remains an insufficient understanding of how their physiochemical dynamics impact printability. Using a model system, N-isopropylacrylamide/Laponite, the electrostatic interactions between Laponite platelets are modified to tune critical rheological properties in order to improve printability. Rheological measurements and X-ray scattering experiments are carried out to monitor the nano/micro-structural dynamics and complex physicochemical interactions of Laponite as it impacts complex modulus in the linear region, flow behavior, thixotropy, and yield stress of the composite ink. Modification of the electrostatic interactions between platelets reduces the yieldmore » stress of the material, while maintaining a complex microstructure that allows for sufficient recovery times upon removal of stress to form stable, and thus printable, filaments. A printing-centric approach is established based on a fundamental understanding of electrostatic inter-particle interactions, harnessing the innate microstructure of Laponite in 3D direct-ink writing of composites.« less

Vibrational spectroscopic determination of local solvent electric field, solute-solvent electrostatic interaction energy, and their fluctuation amplitudes.

PubMed

Lee, Hochan; Lee, Gayeon; Jeon, Jonggu; Cho, Minhaeng

2012-01-12

IR probes have been extensively used to monitor local electrostatic and solvation dynamics. Particularly, their vibrational frequencies are highly sensitive to local solvent electric field around an IR probe. Here, we show that the experimentally measured vibrational frequency shifts can be inversely used to determine local electric potential distribution and solute-solvent electrostatic interaction energy. In addition, the upper limits of their fluctuation amplitudes are estimated by using the vibrational bandwidths. Applying this method to fully deuterated N-methylacetamide (NMA) in D(2)O and examining the solvatochromic effects on the amide I' and II' mode frequencies, we found that the solvent electric potential difference between O(═C) and D(-N) atoms of the peptide bond is about 5.4 V, and thus, the approximate solvent electric field produced by surrounding water molecules on the NMA is 172 MV/cm on average if the molecular geometry is taken into account. The solute-solvent electrostatic interaction energy is estimated to be -137 kJ/mol, by considering electric dipole-electric field interaction. Furthermore, their root-mean-square fluctuation amplitudes are as large as 1.6 V, 52 MV/cm, and 41 kJ/mol, respectively. We found that the water electric potential on a peptide bond is spatially nonhomogeneous and that the fluctuation in the electrostatic peptide-water interaction energy is about 10 times larger than the thermal energy at room temperature. This indicates that the peptide-solvent interactions are indeed important for the activation of chemical reactions in aqueous solution.

Fluorescence turn-on responses of anionic and cationic conjugated polymers toward proteins: effect of electrostatic and hydrophobic interactions.

PubMed

Pu, Kan-Yi; Liu, Bin

2010-03-11

Cationic and anionic poly(fluorenyleneethynylene-alt-benzothiadiazole)s (PFEBTs) are designed and synthesized via Sonagashira coupling reaction to show light-up signatures toward proteins. Due to the charge transfer character of the excited states, the fluorescence of PFEBTs is very weak in aqueous solution, while their yellow fluorescence can be enhanced by polymer aggregation. PFEBTs show fluorescence turn-on rather than fluorescence quenching upon complexation with proteins. Both electrostatic and hydrophobic interactions between PFEBTs and proteins are found to improve the polymer fluorescence, the extent of which is dependent on the nature of the polymer and the protein. Changes in solution pH adjust the net charges of proteins, providing an effective way to manipulate electrostatic interactions and in turn the increment in the polymer fluorescence. In addition, the effect of protein digestion on the fluorescence of polymer/protein complexes is probed. The results indicate that electrostatic interaction induced polymer fluorescence increase cannot be substantially reduced through cleaving protein into peptide fragments. In contrast, hydrophobic interactions, mainly determined by the hydrophobicity of proteins, can be minimized by digestion, imparting a light-off signature for the polymer/protein complexes. This study thus not only highlights the opportunities of exerting nonspecific interactions for protein sensing but also reveals significant implications for biosensor design.

Self organization of exotic oil-in-oil phases driven by tunable electrohydrodynamics

PubMed Central

Varshney, Atul; Ghosh, Shankar; Bhattacharya, S.; Yethiraj, Anand

2012-01-01

Self organization of large-scale structures in nature - either coherent structures like crystals, or incoherent dynamic structures like clouds - is governed by long-range interactions. In many problems, hydrodynamics and electrostatics are the source of such long-range interactions. The tuning of electrostatic interactions has helped to elucidate when coherent crystalline structures or incoherent amorphous structures form in colloidal systems. However, there is little understanding of self organization in situations where both electrostatic and hydrodynamic interactions are present. We present a minimal two-component oil-in-oil model system where we can control the strength and lengthscale of the electrohydrodynamic interactions by tuning the amplitude and frequency of the imposed electric field. As a function of the hydrodynamic lengthscale, we observe a rich phenomenology of exotic structure and dynamics, from incoherent cloud-like structures and chaotic droplet dynamics, to polyhedral droplet phases, to coherent droplet arrays. PMID:23071902

Interference between Triplex and Protein Binding to Distal Sites on Supercoiled DNA.

PubMed

Noy, Agnes; Maxwell, Anthony; Harris, Sarah A

2017-02-07

We have explored the interdependence of the binding of a DNA triplex and a repressor protein to distal recognition sites on supercoiled DNA minicircles using MD simulations. We observe that the interaction between the two ligands through their influence on their DNA template is determined by a subtle interplay of DNA mechanics and electrostatics, that the changes in flexibility induced by ligand binding play an important role and that supercoiling can instigate additional ligand-DNA contacts that would not be possible in simple linear DNA sequences. Copyright © 2017. Published by Elsevier Inc.

Structural study of surfactant-dependent interaction with protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehan, Sumit; Aswal, Vinod K., E-mail: vkaswal@barc.gov.in; Kohlbrecher, Joachim

2015-06-24

Small-angle neutron scattering (SANS) has been used to study the complex structure of anionic BSA protein with three different (cationic DTAB, anionic SDS and non-ionic C12E10) surfactants. These systems form very different surfactant-dependent complexes. We show that the structure of protein-surfactant complex is initiated by the site-specific electrostatic interaction between the components, followed by the hydrophobic interaction at high surfactant concentrations. It is also found that hydrophobic interaction is preferred over the electrostatic interaction in deciding the resultant structure of protein-surfactant complexes.

Structural study of surfactant-dependent interaction with protein

NASA Astrophysics Data System (ADS)

Mehan, Sumit; Aswal, Vinod K.; Kohlbrecher, Joachim

2015-06-01

Small-angle neutron scattering (SANS) has been used to study the complex structure of anionic BSA protein with three different (cationic DTAB, anionic SDS and non-ionic C12E10) surfactants. These systems form very different surfactant-dependent complexes. We show that the structure of protein-surfactant complex is initiated by the site-specific electrostatic interaction between the components, followed by the hydrophobic interaction at high surfactant concentrations. It is also found that hydrophobic interaction is preferred over the electrostatic interaction in deciding the resultant structure of protein-surfactant complexes.

The role of electrostatic interactions in protease surface diffusion and the consequence for interfacial biocatalysis.

PubMed

Feller, Bob E; Kellis, James T; Cascão-Pereira, Luis G; Robertson, Channing R; Frank, Curtis W

2010-12-21

This study examines the influence of electrostatic interactions on enzyme surface diffusion and the contribution of diffusion to interfacial biocatalysis. Surface diffusion, adsorption, and reaction were investigated on an immobilized bovine serum albumin (BSA) multilayer substrate over a range of solution ionic strength values. Interfacial charge of the enzyme and substrate surface was maintained by performing the measurements at a fixed pH; therefore, electrostatic interactions were manipulated by changing the ionic strength. The interfacial processes were investigated using a combination of techniques: fluorescence recovery after photobleaching, surface plasmon resonance, and surface plasmon fluorescence spectroscopy. We used an enzyme charge ladder with a net charge ranging from -2 to +4 with respect to the parent to systematically probe the contribution of electrostatics in interfacial enzyme biocatalysis on a charged substrate. The correlation between reaction rate and adsorption was determined for each charge variant within the ladder, each of which displayed a maximum rate at an intermediate surface concentration. Both the maximum reaction rate and adsorption value at which this maximum rate occurs increased in magnitude for the more positive variants. In addition, the specific enzyme activity increased as the level of adsorption decreased, and for the lowest adsorption values, the specific enzyme activity was enhanced compared to the trend at higher surface concentrations. At a fixed level of adsorption, the specific enzyme activity increased with positive enzyme charge; however, this effect offers diminishing returns as the enzyme becomes more highly charged. We examined the effect of electrostatic interactions on surface diffusion. As the binding affinity was reduced by increasing the solution ionic strength, thus weakening electrostatic interaction, the rate of surface diffusion increased considerably. The enhancement in specific activity achieved at the lowest adsorption values is explained by the substantial rise in surface diffusion at high ionic strength due to decreased interactions with the surface. Overall, knowledge of the electrostatic interactions can be used to control surface parameters such as surface concentration and surface diffusion, which intimately correlate with surface biocatalysis. We propose that the maximum reaction rate results from a balance between adsorption and surface diffusion. The above finding suggests enzyme engineering and process design strategies for improving interfacial biocatalysis in industrial, pharmaceutical, and food applications.

Helping Lower Secondary Students Develop Conceptual Understanding of Electrostatic Forces

ERIC Educational Resources Information Center

Moynihan, Richard; van Kampen, Paul; Finlayson, Odilla; McLoughlin, Eilish

2016-01-01

This article describes the development of a lesson sequence that supports secondary-level students to construct an explanatory model for electrostatic attraction using a guided enquiry method. The students examine electrostatic interactions at a macro level and explain the phenomena at the atomic level. Pre-tests, post-tests, homework assignments…

Calorimetric and spectroscopic studies of the interaction between zidovudine and human serum albumin

NASA Astrophysics Data System (ADS)

Pîrnău, Adrian; Mic, Mihaela; Neamţu, Silvia; Floare, Călin G.; Bogdan, Mircea

2018-02-01

A quantitative analysis of the interaction between zidovudine (AZT) and human serum albumin (HSA) was achieved using Isothermal titration calorimetry (ITC) in combination with fluorescence and 1H NMR spectroscopy. ITC directly measure the heat during a biomolecular binding event and gave us thermodynamic parameters and the characteristic association constant. By fluorescence quenching, the binding parameters of AZT-HSA interaction was determined and location to binding site I of HSA was confirmed. Via T1 NMR selective relaxation time measurements the drug-protein binding extent was evaluated as dissociation constants Kd and the involvement of azido moiety of zidovudine in molecular complex formation was put in evidence. All three methods indicated a very weak binding interaction. The association constant determined by ITC (3.58 × 102 M- 1) is supported by fluorescence quenching data (2.74 × 102 M- 1). The thermodynamic signature indicates that at least hydrophobic and electrostatic type interactions played a main role in the binding process.

Investigation on the interaction between an antimicrobial in aquaculture, malachite green and hemocyanin from mud crab Scylla paramamosain.

PubMed

Li, Zhenxing; Tang, Boping; Zhang, Hongmei

2015-01-25

Interaction between malachite green and hemocyanin of crab plays a crucial role in the metabolism, distribution, and efficacy of toxic dyes in aquaculture. The mechanism of interaction between malachite green and Hc from mud crab was studied by using multi-spectral methods and molecular modeling in this work. The spectroscopic and thermodynamic data show that the interaction is a spontaneous process with the estimated enthalpy and entropy changes of -14.85(±1.86) kJ mol(-1) and 30.38(±5.21) J mol(-1) K(-1), respectively. The binding sites of malachite green in hemocyanin mainly locate in the interface of protein. The hydrophobic and electrostatic forces are the primary contributors to the interaction between hemocyanin and malachite green. The results of ultraviolet-vis absorbance, circular dichroism, and synchronous fluorescence spectroscopy suggest that the binding of malachite green to hemocyanin induces some conformational changes of protein. Copyright © 2014 Elsevier B.V. All rights reserved.

Kinetics and thermodynamics of interaction between sulfonamide antibiotics and humic acids: Surface plasmon resonance and isothermal titration microcalorimetry analysis.

PubMed

Xu, Juan; Yu, Han-Qing; Sheng, Guo-Ping

2016-01-25

The presence of sulfonamide antibiotics in the environments has been recognized as a crucial issue. Their migration and transformation in the environment is determined by natural organic matters that widely exist in natural water and soil. In this study, the kinetics and thermodynamics of interactions between humic acids (HA) and sulfamethazine (SMZ) were investigated by employing surface plasmon resonance (SPR) combined with isothermal titration microcalorimetry (ITC) technologies. Results show that SMZ could be effectively bound with HA. The binding strength could be enhanced by increasing ionic strength and decreasing temperature. High pH was not favorable for the interaction. Hydrogen bond and electrostatic interaction may play important roles in driving the binding process, with auxiliary contribution from hydrophobic interaction. The results implied that HA existed in the environment may have a significant influence on the migration and transformation of organic pollutants through the binding process. Copyright © 2015 Elsevier B.V. All rights reserved.

Phenylboronate chromatography selectively separates glycoproteins through the manipulation of electrostatic, charge transfer, and cis-diol interactions.

PubMed

Carvalho, Rimenys J; Woo, James; Aires-Barros, M Raquel; Cramer, Steven M; Azevedo, Ana M

2014-10-01

Phenylboronate chromatography (PBC) has been applied for several years, however details regarding the mechanisms of interactions between the ligand and biomolecules are still scarce. The goal of this work is to investigate the various chemical interactions between proteins and their ligands, using a protein library containing both glycosylated and nonglycosylated proteins. Differences in the adsorption of these proteins over a pH range from 4 to 9 were related to two main properties: charge and presence of glycans. Acidic or neutral proteins were strongly adsorbed below pH 8 although the uncharged trigonal form of phenylboronate (PB) is less susceptible to forming electrostatic and cis-diol interactions with proteins. The glycosylated proteins were only adsorbed above pH 8 when the electrostatic repulsion between the boronate anion and the protein surface was mitigated (at 200 mM NaCl). All basic proteins were highly adsorbed above pH 8 with PB also acting as a cation-exchanger with binding occurring through electrostatic interactions. Batch adsorption performed at acidic conditions in the presence of Lewis base showed that charge-transfer interactions are critical for protein retention. This study demonstrates the multimodal interaction of PBC, which can be a selective tool for separation of different classes of proteins. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of the influence of the internal aqueous solvent structure on electrostatic interactions at the protein-solvent interface by nonlocal continuum electrostatic approach.

PubMed

Rubinstein, Alexander; Sherman, Simon

The dielectric properties of the polar solvent on the protein-solvent interface at small intercharge distances are still poorly explored. To deconvolute this problem and to evaluate the pair-wise electrostatic interaction (PEI) energies of the point charges located at the protein-solvent interface we used a nonlocal (NL) electrostatic approach along with a static NL dielectric response function of water. The influence of the aqueous solvent microstructure (determined by a strong nonelectrostatic correlation effect between water dipoles within the orientational Debye polarization mode) on electrostatic interactions at the interface was studied in our work. It was shown that the PEI energies can be significantly higher than the energies evaluated by the classical (local) consideration, treating water molecules as belonging to the bulk solvent with a high dielectric constant. Our analysis points to the existence of a rather extended, effective low-dielectric interfacial water shell on the protein surface. The main dielectric properties of this shell (effective thickness together with distance- and orientation-dependent dielectric permittivity function) were evaluated. The dramatic role of this shell was demonstrated when estimating the protein association rate constants.

Optimal charges in lead progression: a structure-based neuraminidase case study.

PubMed

Armstrong, Kathryn A; Tidor, Bruce; Cheng, Alan C

2006-04-20

Collective experience in structure-based lead progression has found electrostatic interactions to be more difficult to optimize than shape-based ones. A major reason for this is that the net electrostatic contribution observed includes a significant nonintuitive desolvation component in addition to the more intuitive intermolecular interaction component. To investigate whether knowledge of the ligand optimal charge distribution can facilitate more intuitive design of electrostatic interactions, we took a series of small-molecule influenza neuraminidase inhibitors with known protein cocrystal structures and calculated the difference between the optimal and actual charge distributions. This difference from the electrostatic optimum correlates with the calculated electrostatic contribution to binding (r(2) = 0.94) despite small changes in binding modes caused by chemical substitutions, suggesting that the optimal charge distribution is a useful design goal. Furthermore, detailed suggestions for chemical modification generated by this approach are in many cases consistent with observed improvements in binding affinity, and the method appears to be useful despite discrete chemical constraints. Taken together, these results suggest that charge optimization is useful in facilitating generation of compound ideas in lead optimization. Our results also provide insight into design of neuraminidase inhibitors.

Electrostatic interaction between stereocilia: II. Influence on the mechanical properties of the hair bundle.

PubMed

Dolgobrodov, S G; Lukashkin, A N; Russell, I J

2000-12-01

This paper is based on our model [Dolgobrodov et al., 2000. Hear. Res., submitted for publication] in which we examine the significance of the polyanionic surface layers of stereocilia for electrostatic interaction between them. We analyse how electrostatic forces modify the mechanical properties of the sensory hair bundle. Different charge distribution profiles within the glycocalyx are considered. When modelling a typical experiment on bundle stiffness measurements, applying an external force to the tallest row of stereocilia shows that the asymptotic stiffness of the hair bundle for negative displacements is always larger than the asymptotic stiffness for positive displacements. This increase in stiffness is monotonic for even charge distribution and shows local minima when the negative charge is concentrated in a thinner layer within the cell coat. The minima can also originate from the co-operative effect of electrostatic repulsion and inter-ciliary links with non-linear mechanical properties. Existing experimental observations are compared with the predictions of the model. We conclude that the forces of electrostatic interaction between stereocilia may influence the mechanical properties of the hair bundle and, being strongly non-linear, contribute to the non-linear phenomena, which have been recorded from the auditory periphery.

PHEPS: web-based pH-dependent Protein Electrostatics Server

PubMed Central

Kantardjiev, Alexander A.; Atanasov, Boris P.

2006-01-01

PHEPS (pH-dependent Protein Electrostatics Server) is a web service for fast prediction and experiment planning support, as well as for correlation and analysis of experimentally obtained results, reflecting charge-dependent phenomena in globular proteins. Its implementation is based on long-term experience (PHEI package) and the need to explain measured physicochemical characteristics at the level of protein atomic structure. The approach is semi-empirical and based on a mean field scheme for description and evaluation of global and local pH-dependent electrostatic properties: protein proton binding; ionic sites proton population; free energy electrostatic term; ionic groups proton affinities (pKa,i) and their Coulomb interaction with whole charge multipole; electrostatic potential of whole molecule at fixed pH and pH-dependent local electrostatic potentials at user-defined set of points. The speed of calculation is based on fast determination of distance-dependent pair charge-charge interactions as empirical three exponential function that covers charge–charge, charge–dipole and dipole–dipole contributions. After atomic coordinates input, all standard parameters are used as defaults to facilitate non-experienced users. Special attention was given to interactive addition of non-polypeptide charges, extra ionizable groups with intrinsic pKas or fixed ions. The output information is given as plain-text, readable by ‘RasMol’, ‘Origin’ and the like. The PHEPS server is accessible at . PMID:16845042

Long-range electrostatic screening in ionic liquids

PubMed Central

Gebbie, Matthew A.; Dobbs, Howard A.; Valtiner, Markus; Israelachvili, Jacob N.

2015-01-01

Electrolyte solutions with high concentrations of ions are prevalent in biological systems and energy storage technologies. Nevertheless, the high interaction free energy and long-range nature of electrostatic interactions makes the development of a general conceptual picture of concentrated electrolytes a significant challenge. In this work, we study ionic liquids, single-component liquids composed solely of ions, in an attempt to provide a novel perspective on electrostatic screening in very high concentration (nonideal) electrolytes. We use temperature-dependent surface force measurements to demonstrate that the long-range, exponentially decaying diffuse double-layer forces observed across ionic liquids exhibit a pronounced temperature dependence: Increasing the temperature decreases the measured exponential (Debye) decay length, implying an increase in the thermally driven effective free-ion concentration in the bulk ionic liquids. We use our quantitative results to propose a general model of long-range electrostatic screening in ionic liquids, where thermally activated charge fluctuations, either free ions or correlated domains (quasiparticles), take on the role of ions in traditional dilute electrolyte solutions. This picture represents a crucial step toward resolving several inconsistencies surrounding electrostatic screening and charge transport in ionic liquids that have impeded progress within the interdisciplinary ionic liquids community. More broadly, our work provides a previously unidentified way of envisioning highly concentrated electrolytes, with implications for diverse areas of inquiry, ranging from designing electrochemical devices to rationalizing electrostatic interactions in biological systems. PMID:26040001

Origin of selenium–gold interaction in F{sub 2}CSe⋯AuY (Y = CN, F, Cl, Br, OH, and CH{sub 3}): Synergistic effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Xin; Yang, Yu-Ping; Li, Qing-Zhong, E-mail: liqingzhong1990@sina.com, E-mail: lihaibei@sdu.edu.cn

Selenium–gold interaction plays an important role in crystal materials, molecular self-assembly, and pharmacochemistry involving gold. In this paper, we unveiled the mechanism and nature of selenium–gold interaction by studying complexes F{sub 2}CSe⋯AuY (Y = CN, F, Cl, Br, OH, and CH{sub 3}). The results showed that the formation of selenium–gold interaction is mainly attributed to the charge transfer from the lone pair of Se atom to the Au—Y anti-bonding orbital. Energy decomposition analysis indicated that the polarization energy is nearly equivalent to or exceeds the electrostatic term in the selenium–gold interaction. Interestingly, the chalcogen–gold interaction becomes stronger with the increasemore » of chalcogen atomic mass in F{sub 2}CX⋯AuCN (X = O, S, Se, and Te). The cyclic ternary complexes are formed with the introduction of NH{sub 3} into F{sub 2}CSe⋯AuY, in which selenium–gold interaction is weakened and selenium–nitrogen interaction is strengthened due to the synergistic effects.« less

Time-resolved energy transfer in DNA sequence detection using water-soluble conjugated polymers: the role of electrostatic and hydrophobic interactions.

PubMed

Xu, Qing-Hua; Gaylord, Brent S; Wang, Shu; Bazan, Guillermo C; Moses, Daniel; Heeger, Alan J

2004-08-10

We have investigated the energy transfer processes in DNA sequence detection by using cationic conjugated polymers and peptide nucleic acid (PNA) probes with ultrafast pump-dump-emission spectroscopy. Pump-dump-emission spectroscopy provides femtosecond temporal resolution and high sensitivity and avoids interference from the solvent response. The energy transfer from donor (the conjugated polymer) to acceptor (a fluorescent molecule attached to a PNA terminus) has been time resolved. The results indicate that both electrostatic and hydrophobic interactions contribute to the formation of cationic conjugated polymers/PNA-C/DNA complexes. The two interactions result in two different binding conformations. This picture is supported by the average donor-acceptor separations as estimated from time-resolved and steady-state measurements. Electrostatic interactions dominate at low concentrations and in mixed solvents.

Time-resolved energy transfer in DNA sequence detection using water-soluble conjugated polymers: The role of electrostatic and hydrophobic interactions

PubMed Central

Xu, Qing-Hua; Gaylord, Brent S.; Wang, Shu; Bazan, Guillermo C.; Moses, Daniel; Heeger, Alan J.

2004-01-01

We have investigated the energy transfer processes in DNA sequence detection by using cationic conjugated polymers and peptide nucleic acid (PNA) probes with ultrafast pump-dump-emission spectroscopy. Pump-dump-emission spectroscopy provides femtosecond temporal resolution and high sensitivity and avoids interference from the solvent response. The energy transfer from donor (the conjugated polymer) to acceptor (a fluorescent molecule attached to a PNA terminus) has been time resolved. The results indicate that both electrostatic and hydrophobic interactions contribute to the formation of cationic conjugated polymers/PNA-C/DNA complexes. The two interactions result in two different binding conformations. This picture is supported by the average donor–acceptor separations as estimated from time-resolved and steady-state measurements. Electrostatic interactions dominate at low concentrations and in mixed solvents. PMID:15282375

Research and Development of Electrostatic Accelerometers for Space Science Missions at HUST.

PubMed

Bai, Yanzheng; Li, Zhuxi; Hu, Ming; Liu, Li; Qu, Shaobo; Tan, Dingyin; Tu, Haibo; Wu, Shuchao; Yin, Hang; Li, Hongyin; Zhou, Zebing

2017-08-23

High-precision electrostatic accelerometers have achieved remarkable success in satellite Earth gravity field recovery missions. Ultralow-noise inertial sensors play important roles in space gravitational wave detection missions such as the Laser Interferometer Space Antenna (LISA) mission, and key technologies have been verified in the LISA Pathfinder mission. Meanwhile, at Huazhong University of Science and Technology (HUST, China), a space accelerometer and inertial sensor based on capacitive sensors and the electrostatic control technique have also been studied and developed independently for more than 16 years. In this paper, we review the operational principle, application, and requirements of the electrostatic accelerometer and inertial sensor in different space missions. The development and progress of a space electrostatic accelerometer at HUST, including ground investigation and space verification are presented.

Research and Development of Electrostatic Accelerometers for Space Science Missions at HUST

PubMed Central

Bai, Yanzheng; Li, Zhuxi; Hu, Ming; Liu, Li; Qu, Shaobo; Tan, Dingyin; Tu, Haibo; Wu, Shuchao; Yin, Hang; Li, Hongyin; Zhou, Zebing

2017-01-01

High-precision electrostatic accelerometers have achieved remarkable success in satellite Earth gravity field recovery missions. Ultralow-noise inertial sensors play important roles in space gravitational wave detection missions such as the Laser Interferometer Space Antenna (LISA) mission, and key technologies have been verified in the LISA Pathfinder mission. Meanwhile, at Huazhong University of Science and Technology (HUST, China), a space accelerometer and inertial sensor based on capacitive sensors and the electrostatic control technique have also been studied and developed independently for more than 16 years. In this paper, we review the operational principle, application, and requirements of the electrostatic accelerometer and inertial sensor in different space missions. The development and progress of a space electrostatic accelerometer at HUST, including ground investigation and space verification are presented. PMID:28832538

Protein-membrane electrostatic interactions: Application of the Lekner summation technique

NASA Astrophysics Data System (ADS)

Juffer, André H.; Shepherd, Craig M.; Vogel, Hans J.

2001-01-01

A model has been developed to calculate the electrostatic interaction between biomolecules and lipid bilayers. The effect of ionic strength is included by means of explicit ions, while water is described as a background continuum. The bilayer is considered at the atomic level. The Lekner summation technique is employed to calculate the long-range electrostatic interactions. The new method is employed to estimate the electrostatic contribution to the free energy of binding of sandostatin, a cyclic eight-residue analogue of the peptide hormone somatostatin, to lipid bilayers with thermodynamic integration. Monte Carlo simulation techniques were employed to determine ion distributions and peptide orientations. Both neutral as well as negatively charged lipid bilayers were used. An error analysis to judge the quality of the computation is also presented. The applicability of the Lekner summation technique to combine it with computer simulation models that simulate the adsorption of peptides (and proteins) into the interfacial region of lipid bilayers is discussed.

The ‘non-Coulombic’ character of classical electrostatic interaction between charges near interfaces

NASA Astrophysics Data System (ADS)

Gabovich, A. M.; Voitenko, A. I.

2018-07-01

The textbook problem of classical electrostatics concerning the charge–charge interaction energy W in a two-layer system is revisited. In particular, the actual dependence of W on the horizontal distance L between the charges located at the same distance x from the interface is shown to substantially differ from the original Coulomb law due to image charges. The deviations are governed by the ratio L/x and the ratio between the dielectric constants of adjacent media. Thus, the dependence W(L) is never conventionally Coulombic (∼L ‑1) and may even be close to a dipole–dipole one (∼L ‑3). Although these results are implicitly contained in the well-known formulas, they are often overlooked while teaching electrostatics. The results are of interest not only from a purely academic viewpoint but are important for modern surface science, where the electrostatic contribution to the ion–ion interaction is often treated as Coulombic without any reservations.

Inductive and electrostatic acceleration in relativistic jet-plasma interactions.

PubMed

Ng, Johnny S T; Noble, Robert J

2006-03-24

We report on the observation of rapid particle acceleration in numerical simulations of relativistic jet-plasma interactions and discuss the underlying mechanisms. The dynamics of a charge-neutral, narrow, electron-positron jet propagating through an unmagnetized electron-ion plasma was investigated using a three-dimensional, electromagnetic, particle-in-cell computer code. The interaction excited magnetic filamentation as well as electrostatic plasma instabilities. In some cases, the longitudinal electric fields generated inductively and electrostatically reached the cold plasma-wave-breaking limit, and the longitudinal momentum of about half the positrons increased by 50% with a maximum gain exceeding a factor of 2 during the simulation period. Particle acceleration via these mechanisms occurred when the criteria for Weibel instability were satisfied.

Effect of open metal sites on adsorption of polar and nonpolar molecules in metal-organic framework Cu-BTC.

PubMed

Karra, Jagadeswara R; Walton, Krista S

2008-08-19

Atomistic grand canonical Monte Carlo simulations were performed in this work to investigate the role of open copper sites of Cu-BTC in affecting the separation of carbon monoxide from binary mixtures containing methane, nitrogen, or hydrogen. Mixtures containing 5%, 50%, or 95% CO were examined. The simulations show that electrostatic interactions between the CO dipole and the partial charges on the metal-organic framework (MOF) atoms dominate the adsorption mechanism. The binary simulations show that Cu-BTC is quite selective for CO over hydrogen and nitrogen for all three mixture compositions at 298 K. The removal of CO from a 5% mixture with methane is slightly enhanced by the electrostatic interactions of CO with the copper sites. However, the pore space of Cu-BTC is large enough to accommodate both molecules at their pure-component loadings, and in general, Cu-BTC exhibits no significant selectivity for CO over methane for the equimolar and 95% mixtures. On the basis of the pure-component and low-concentration behavior of CO, the results indicate that MOFs with open metal sites have the potential for enhancing adsorption separations of molecules of differing polarities, but the pore size relative to the sorbate size will also play a significant role.

Role of electrostatic interactions in the toxicity of titanium dioxide nanoparticles toward Escherichia coli.

PubMed

Pagnout, Christophe; Jomini, Stéphane; Dadhwal, Mandeep; Caillet, Céline; Thomas, Fabien; Bauda, Pascale

2012-04-01

The increasing production and use of titanium dioxide nanoparticles (NP-TiO(2)) has led to concerns about their possible impact on the environment. Bacteria play crucial roles in ecosystem processes and may be subject to the toxicity of these nanoparticles. In this study, we showed that at low ionic strength, the cell viability of Escherichia coli was more severely affected at pH 5.5 than at pH 7.0 and pH 9.5. At pH 5.5, nanoparticles (positively charged) strongly interacted with the bacterial cells (negatively charged) and accumulated on their surfaces. This phenomenon was observed in a much lower degree at pH 7.0 (NP-TiO(2) neutrally charged and cells negatively charged) and pH 9.5 (both NP-TiO(2) and cells negatively charged). It was also shown that the addition of electrolytes (NaCl, CaCl(2), Na(2)SO(4)) resulted in a gradual reduction of the NP-TiO(2) toxicity at pH 5.5 and an increase in this toxicity at pH 9.5, which was closely related to the reduction of the NP-TiO(2) and bacterial cell electrostatic charges. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Model Dependency of TMAO's Counteracting Effect Against Action of Urea: Kast Model versus Osmotic Model of TMAO.

PubMed

Borgohain, Gargi; Paul, Sandip

2016-03-10

Classical molecular dynamics simulation of GB1 peptide (a 16-residue β-hairpin) in different osmotic environments is studied. Urea is used for denaturation of the peptide, and trimethylamine-N-oxide (TMAO) is used to offset the effect of urea. Protein-urea electrostatic interactions are found to play a major role in protein-denaturation. To emphasize on protein protecting action of TMAO against urea, two different models of TMAO are used, viz., the Kast model and the Osmotic model. We observe that the Osmotic model of TMAO gives the best protection to counteract urea's action when used in ratio 1:2 of urea:TMAO (i.e., reverse ratio). This is because the presence of TMAO makes urea-protein electrostatic interactions more unfavorable. Preferential solvation of TMAO molecules by urea (and water) molecules is also observed, which causes depletion in the number of urea molecules in the vicinity of the protein. The calculations of intraprotein hydrogen bonds between different residues of protein further reveal the breaking of backbone hydrogen bonds of residues 2 and 15 in the presence of urea, and the same is preserved in the presence of TMAO. Free energy landscapes show that the narrowest distribution is obtained for the osmotic TMAO model when used in reverse ratio.

Polarization Coupling in Ferroelectric Multilayers as a Function of Interface Charge Concentration

NASA Astrophysics Data System (ADS)

Okatan, Mahmut; Mantese, Joseph; Alpay, Pamir

2009-03-01

Intriguing properties of multilayered and graded ferroelectrics follow from the electrostatic and electromechanical interactions. The strength of the interlayer coupling depends on the concentration of interfacial defects with short-range local electrostatic fields. Defects may locally relax polarization differences and thus reduce the commensurate bound charge concentration at the interlayer interfaces. In this talk, we develop a theoretical analysis based on non-linear thermodynamics coupled with basic electrostatic relations to understand the role of charge compensation at the interlayer interfaces. The results show multilayered ferroelectrics with systematic variations in the composition may display a colossal dielectric response depending upon the interlayer electrostatic interactions. It is expected that other properties such as the pyroelectric and piezoelectric response will yield concomitant increases through the dielectric permittivity.

Electrostatic interactions between diffuse soft multi-layered (bio)particles: beyond Debye-Hückel approximation and Deryagin formulation.

PubMed

Duval, Jérôme F L; Merlin, Jenny; Narayana, Puranam A L

2011-01-21

We report a steady-state theory for the evaluation of electrostatic interactions between identical or dissimilar spherical soft multi-layered (bio)particles, e.g. microgels or microorganisms. These generally consist of a rigid core surrounded by concentric ion-permeable layers that may differ in thickness, soft material density, chemical composition and degree of dissociation for the ionogenic groups. The formalism allows the account of diffuse interphases where distributions of ionogenic groups from one layer to the other are position-dependent. The model is valid for any number of ion-permeable layers around the core of the interacting soft particles and covers all limiting situations in terms of nature of interacting particles, i.e. homo- and hetero-interactions between hard, soft or entirely porous colloids. The theory is based on a rigorous numerical solution of the non-linearized Poisson-Boltzmann equation including radial and angular distortions of the electric field distribution within and outside the interacting soft particles in approach. The Gibbs energy of electrostatic interaction is obtained from a general expression derived following the method by Verwey and Overbeek based on appropriate electric double layer charging mechanisms. Original analytical solutions are provided here for cases where interaction takes place between soft multi-layered particles whose size and charge density are in line with Deryagin treatment and Debye-Hückel approximation. These situations include interactions between hard and soft particles, hard plate and soft particle or soft plate and soft particle. The flexibility of the formalism is highlighted by the discussion of few situations which clearly illustrate that electrostatic interaction between multi-layered particles may be partly or predominantly governed by potential distribution within the most internal layers. A major consequence is that both amplitude and sign of Gibbs electrostatic interaction energy may dramatically change depending on the interplay between characteristic Debye length, thickness of ion-permeable layers and their respective protolytic features (e.g. location, magnitude and sign of charge density). This formalism extends a recent model by Ohshima which is strictly limited to interaction between soft mono-shell particles within Deryagin and Debye-Hückel approximations under conditions where ionizable sites are completely dissociated.

Insights into the selective binding and toxic mechanism of microcystin to catalase

NASA Astrophysics Data System (ADS)

Hu, Yuandong; Da, Liangjun

2014-03-01

Microcystin is a sort of cyclic nonribosomal peptides produced by cyanobacteria. It is cyanotoxin, which can be very toxic for plants and animals including humans. The present study evaluated the interaction of microcystin and catalase, under physiological conditions by means of fluorescence, three-dimensional (3D) fluorescence, circular dichroism (CD), Fourier Transform infrared (FT-IR) spectroscopy, and enzymatic reactionkinetic techniques. The fluorescence data showed that microcystin could bind to catalase to form a complex. The binding process was a spontaneous molecular interaction procedure, in which electrostatic interactions played a major role. Energy transfer and fluorescence studies proved the existence of a static binding process. Additionally, as shown by the three-dimensional fluorescence, CD and FT-IR results, microcystin could lead to conformational and microenvironmental changes of the protein, which may affect the physiological functions of catalase. The work provides important insights into the toxicity mechanism of microcystin in vivo.

Spectroscopic and molecular modeling studies of the interaction between cytidine and human serum albumin and its analytical application.

PubMed

Cui, Fengling; Wang, Junli; Yao, Xiaojun; Wang, Li; Zhang, Qiangzhai; Qu, Guirong

In this study, the interaction between cytidine and human serum albumin (HSA) was investigated for the first time by fluorescence spectroscopy in combination with UV absorption spectrum and molecular modeling under simulative physiological conditions. Experimental results indicated that cytidine had a strong ability to quench the intrinsic fluorescence of human serum albumin. The binding constants (K) at different temperatures, thermodynamic parameter enthalpy changes (DeltaH) and entropy changes (DeltaS) of HSA-cytidine had been calculated according to the relevant fluorescence data, which indicated that the hydrophobic and electrostatic interactions played a major role, which was in agreement with the results of molecular modeling study. In addition, the effects of other ions on the binding constants were also studied. Furthermore, synchronous fluorescence technology was successfully applied to the determination of human serum albumin added into the cytidine solution.

Molecular modeling and multispectroscopic studies of the interaction of mesalamine with bovine serum albumin

NASA Astrophysics Data System (ADS)

Shahabadi, Nahid; Fili, Soraya Moradi

2014-01-01

The interaction of mesalamine (5-aminosalicylic acid (5-ASA)) with bovine serum albumin (BSA) was investigated by fluorescence quenching, absorption spectroscopy, circular dichroism (CD) techniques, and molecular docking. Thermodynamic parameters (ΔH < 0 and ΔS 0) indicated that the hydrogen bond and electrostatic forces played the major role in the binding of 5-ASA to BSA. The results of CD and UV-vis spectroscopy showed that the binding of this drug to BSA induces some conformational changes in BSA. Displacement experiments predicted that the binding of 5-ASA to BSA is located within domain III, Sudlows site 2, that these observations were substantiated by molecular docking studies. In addition, the docking result shows that the 5-ASA in its anionic form mainly interacts with Gln-416 residue through one hydrogen bond between H atom of 5-ASA anion and the adjacent O atom of the hydroxyl group of Gln-416.

Conformational and stereoelectronic investigation in 1,2-difluoropropane: The gauche effect

NASA Astrophysics Data System (ADS)

Bitencourt, Michelle; Freitas, Matheus P.; Rittner, Roberto

2007-09-01

The effect of attaching an additional fluorine atom at C-2 in 1-fluoropropane (FP), giving 1,2-difluoropropane (DFP), on its conformational equilibrium, is theoretically evaluated. This substitution causes critical implications on the conformer stabilities of DFP (TG, GT and GG conformations) and the steric and electrostatic interactions should favor the conformer with fluorine atoms trans. However, the gauche effect plays a major role in describing the energies balance in DFP, shifting the equilibrium towards the conformation in which the two fluorine atoms are gauche. The origin of this effect is discussed through an NBO analysis, which allows the evaluation of both classical and non-classical (hyperconjugation and bent bonds) interactions as the prevailing factors governing the conformational equilibrium of molecules containing the 1,2-difluoroethane fragment.

Chemical bonding in silicon-carbene complexes.

PubMed

Liu, Z

2009-06-04

The bonding situations in the newly synthesized silicon-carbene complexes with formulas L:SiCl4, L:(Cl)Si-Si(Cl):L, and L:Si=Si:L (where L: is an N-heterocyclic carbene), are reported using density functional theory at the BP86/TZ2P level. The bonding analysis clearly shows that the bonding situation in the silicon-carbene complexes cannot be described in terms of donor-acceptor interactions depicted in the Dewar-Chatt-Duncanson model. The energy decomposition analysis (EDA) shows that the electrostatic attraction plays an important or even dominant role for the Si-C(carbene) binding interactions in the silicon-carbene complexes. That the molecular orbitals of the silicon-carbene complexes are lower in energy than the parent orbitals of carbenes indicates that these complexes are better described as stabilized carbene complexes.

Counting the ions surrounding nucleic acids

PubMed Central

2017-01-01

Abstract Nucleic acids are strongly negatively charged, and thus electrostatic interactions—screened by ions in solution—play an important role in governing their ability to fold and participate in biomolecular interactions. The negative charge creates a region, known as the ion atmosphere, in which cation and anion concentrations are perturbed from their bulk values. Ion counting experiments quantify the ion atmosphere by measuring the preferential ion interaction coefficient: the net total number of excess ions above, or below, the number expected due to the bulk concentration. The results of such studies provide important constraints on theories, which typically predict the full three-dimensional distribution of the screening cloud. This article reviews the state of nucleic acid ion counting measurements and critically analyzes their ability to test both analytical and simulation-based models. PMID:28034959

Insight into the binding mechanism of imipenem to human serum albumin by spectroscopic and computational approaches.

PubMed

Rehman, Md Tabish; Shamsi, Hira; Khan, Asad U

2014-06-02

The mechanism of interaction between imipenem and HSA was investigated by various techniques like fluorescence, UV.vis absorbance, FRET, circular dichroism, urea denaturation, enzyme kinetics, ITC, and molecular docking. We found that imipenem binds to HSA at a high affinity site located in subdomain IIIA (Sudlow's site I) and a low affinity site located in subdomain IIA.IIB. Electrostatic interactions played a vital role along with hydrogen bonding and hydrophobic interactions in stabilizing the imipenem.HSA complex at subdomain IIIA, while only electrostatic and hydrophobic interactions were present at subdomain IIA.IIB. The binding and thermodynamic parameters obtained by ITC showed that the binding of imipenem to HSA was a spontaneous process (ΔGD⁰(D)= -32.31 kJ mol(-1) for high affinity site and ΔGD⁰(D) = -23.02 kJ mol(-1) for low affinity site) with binding constants in the range of 10(4)-10(5) M(-1). Spectroscopic investigation revealed only one binding site of imipenem on HSA (Ka∼10(4) M(-1)). FRET analysis showed that the binding distance between imipenem and HSA (Trp-214) was optimal (r = 4.32 nm) for quenching to occur. Decrease in esterase-like activity of HSA in the presence of imipenem showed that Arg-410 and Tyr-411 of subdomain IIIA (Sudlow's site II) were directly involved in the binding process. CD spectral analysis showed altered conformation of HSA upon imipenem binding. Moreover, the binding of imipenem to subdomain IIIA (Sudlow's site II) of HSA also affected its folding pathway as clear from urea-induced denaturation studies.

The Correlation of Adsorption Behavior between Ciprofloxacin Hydrochloride and the Active Sites of Fe-doped MCM-41.

PubMed

Wu, Ying; Tang, Yiming; Li, Laisheng; Liu, Peihong; Li, Xukai; Chen, Weirui; Xue, Ying

2018-01-01

HIGHLIGHTS Fe incorporation significantly accelerated the adsorption of CPX on MCM-41.Fe leaching can be ignored when pH was higher than 4.0.pH played an important role in CPX adsorption on Fe-MCM-41.Co-effect of CPX and metal cations on Fe-MCM-41 was investigated. Fe-MCM-41s with various molar ratios of silicon to iron (20, 40, 80, and 160) were prepared to investigate adsorption properties of ciprofloxacin hydrochloride (CPX) in aqueous solutions. Fe-MCM-41s were characterized by transmission electron microscope (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), nitrogen adsorption/desorption isotherms, and infrared spectroscopy (FT-IR). Effects of silicon-iron ratio, adsorbent dosage, pH, and temperature were conducted to explore the adsorption mechanism of CPX on Fe-MCM-41. The results showed that the introduction of iron facilitated the absorption quantity for CPX from 20.04 to 83.33 mg g -1 at 120 min of reaction time, which was mainly attributed to surface complexation. The promotion of hydrophobic effect, electrostatic interactions, and π-π electron donor-acceptor interaction also played coordinate roles in the adsorption process. The experimental kinetic data followed both the pseudo-second-order and intra-particle diffusion models, while the adsorption isotherm data fit well to Freundlich model at high temperature. Thermodynamic study showed that the adsorption was spontaneous. Under the effect of electrostatic interaction, pH of the solution strongly affected CPX adsorption. Five representative metal cations (Ca, Cu, Ni, Pb, and Cd) were chosen to study the effects on CPX adsorption and their complexation. The inhibiting effect of metal cations on CPX adsorption was sequenced in the order of Cu > Ni > Pb > Cd > Ca, which followed the same order as the complexation stability constants between CPX and cations. The Fe-MCM-41 adsorbent possessed excellent reusability for 4 cycles use, suggesting a potential applicability of Fe-MCM-41 to remove CPX in water.

The Correlation of Adsorption Behavior between Ciprofloxacin Hydrochloride and the Active Sites of Fe-doped MCM-41

PubMed Central

Wu, Ying; Tang, Yiming; Li, Laisheng; Liu, Peihong; Li, Xukai; Chen, Weirui; Xue, Ying

2018-01-01

HIGHLIGHTS Fe incorporation significantly accelerated the adsorption of CPX on MCM-41.Fe leaching can be ignored when pH was higher than 4.0.pH played an important role in CPX adsorption on Fe-MCM-41.Co-effect of CPX and metal cations on Fe-MCM-41 was investigated. Fe-MCM-41s with various molar ratios of silicon to iron (20, 40, 80, and 160) were prepared to investigate adsorption properties of ciprofloxacin hydrochloride (CPX) in aqueous solutions. Fe-MCM-41s were characterized by transmission electron microscope (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), nitrogen adsorption/desorption isotherms, and infrared spectroscopy (FT-IR). Effects of silicon-iron ratio, adsorbent dosage, pH, and temperature were conducted to explore the adsorption mechanism of CPX on Fe-MCM-41. The results showed that the introduction of iron facilitated the absorption quantity for CPX from 20.04 to 83.33 mg g−1 at 120 min of reaction time, which was mainly attributed to surface complexation. The promotion of hydrophobic effect, electrostatic interactions, and π-π electron donor-acceptor interaction also played coordinate roles in the adsorption process. The experimental kinetic data followed both the pseudo-second-order and intra-particle diffusion models, while the adsorption isotherm data fit well to Freundlich model at high temperature. Thermodynamic study showed that the adsorption was spontaneous. Under the effect of electrostatic interaction, pH of the solution strongly affected CPX adsorption. Five representative metal cations (Ca, Cu, Ni, Pb, and Cd) were chosen to study the effects on CPX adsorption and their complexation. The inhibiting effect of metal cations on CPX adsorption was sequenced in the order of Cu > Ni > Pb > Cd > Ca, which followed the same order as the complexation stability constants between CPX and cations. The Fe-MCM-41 adsorbent possessed excellent reusability for 4 cycles use, suggesting a potential applicability of Fe-MCM-41 to remove CPX in water. PMID:29468153

Effect of the ordered interfacial water layer in protein complex formation: A nonlocal electrostatic approach

NASA Astrophysics Data System (ADS)

Rubinstein, A.; Sabirianov, R. F.; Mei, W. N.; Namavar, F.; Khoynezhad, A.

2010-08-01

Using a nonlocal electrostatic approach that incorporates the short-range structure of the contacting media, we evaluated the electrostatic contribution to the energy of the complex formation of two model proteins. In this study, we have demonstrated that the existence of an ordered interfacial water layer at the protein-solvent interface reduces the charging energy of the proteins in the aqueous solvent, and consequently increases the electrostatic contribution to the protein binding (change in free energy upon the complex formation of two proteins). This is in contrast with the finding of the continuum electrostatic model, which suggests that electrostatic interactions are not strong enough to compensate for the unfavorable desolvation effects.

Effect of the ordered interfacial water layer in protein complex formation: A nonlocal electrostatic approach.

PubMed

Rubinstein, A; Sabirianov, R F; Mei, W N; Namavar, F; Khoynezhad, A

2010-08-01

Using a nonlocal electrostatic approach that incorporates the short-range structure of the contacting media, we evaluated the electrostatic contribution to the energy of the complex formation of two model proteins. In this study, we have demonstrated that the existence of an ordered interfacial water layer at the protein-solvent interface reduces the charging energy of the proteins in the aqueous solvent, and consequently increases the electrostatic contribution to the protein binding (change in free energy upon the complex formation of two proteins). This is in contrast with the finding of the continuum electrostatic model, which suggests that electrostatic interactions are not strong enough to compensate for the unfavorable desolvation effects.

Aggregation in charged nanoparticles solutions induced by different interactions

NASA Astrophysics Data System (ADS)

Abbas, S.; Kumar, Sugam; Aswal, V. K.; Kohlbrecher, J.

2016-05-01

Small-angle neutron scattering (SANS) has been used to study the aggregation of anionic silica nanoparticles as induced through different interactions. The nanoparticle aggregation is induced by addition of salt (NaCl), cationic protein (lysozyme) and non-ionic surfactant (C12E10) employing different kind of interactions. The results show that the interaction in presence of salt can be explained using DLVO theory whereas non-DLVO forces play important role for interaction of nanoparticles with protein and surfactant. The presence of salt screens the repulsion between charged nanoparticles giving rise to a net attraction in the DLVO potential. On the other hand, strong electrostatic attraction between nanoparticle and oppositely charged protein leads to protein-mediated nanoparticle aggregation. In case of non-ionic surfactant, the relatively long-range attractive depletion interaction is found to be responsible for the particle aggregation. Interestingly, the completely different interactions lead to similar kind of aggregate morphology. The nanoparticle aggregates formed are found to have mass fractal nature having a fractal dimension (~2.5) consistent with diffusion limited type of fractal morphology in all three cases.

Aggregation in charged nanoparticles solutions induced by different interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abbas, S.; Kumar, Sugam; Aswal, V. K., E-mail: vkaswal@barc.gov.in

2016-05-23

Small-angle neutron scattering (SANS) has been used to study the aggregation of anionic silica nanoparticles as induced through different interactions. The nanoparticle aggregation is induced by addition of salt (NaCl), cationic protein (lysozyme) and non-ionic surfactant (C12E10) employing different kind of interactions. The results show that the interaction in presence of salt can be explained using DLVO theory whereas non-DLVO forces play important role for interaction of nanoparticles with protein and surfactant. The presence of salt screens the repulsion between charged nanoparticles giving rise to a net attraction in the DLVO potential. On the other hand, strong electrostatic attraction betweenmore » nanoparticle and oppositely charged protein leads to protein-mediated nanoparticle aggregation. In case of non-ionic surfactant, the relatively long-range attractive depletion interaction is found to be responsible for the particle aggregation. Interestingly, the completely different interactions lead to similar kind of aggregate morphology. The nanoparticle aggregates formed are found to have mass fractal nature having a fractal dimension (~2.5) consistent with diffusion limited type of fractal morphology in all three cases.« less

Effect of humic acid on the sorption of perfluorooctane sulfonate (PFOS) and perfluorobutane sulfonate (PFBS) on boehmite.

PubMed

Wang, Fei; Shih, Kaimin; Leckie, James O

2015-01-01

The sorption of PFOS and PFBS on boehmite was significantly retarded by the competitive sorption of humic acid (HA), implying that PFOS and PFBS are likely more mobile in water and groundwater systems enriched with HA. The sorption behavior of PFOS and PFBS on the HA-modified boehmite surface were also found to differ due to their different chain lengths. For a partially HA-modified boehmite surface, the isotherm study showed that PFOS had a much higher maximum sorption capacity than PFBS and that PFOS might possess additional surface interactions besides electrostatic interaction. For a HA-saturated boehmite, a linear sorption isotherm was found for PFOS while nearly no PFBS sorption was observed. This indicates that sorption behavior between PFOS and the sorbed HA on boehmite was dominated by hydrophobic interactions, instead of electrostatic interaction. In addition, a conceptual model combining hydrophobic and electrostatic interaction was established to explain the sorption behavior of PFOS and PFBS on HA-modified boehmite. Finally, the results revealed that the sorption of PFOS and PFBS on HA-modified boehmite is pH-dependent. The neutralization of negative sites on HA-modified boehmite reduced the electrostatic repulsion and enhanced the partitioning of PFBS on the sorbed HA. Copyright © 2014 Elsevier Ltd. All rights reserved.

Experimentally biased model structure of the Hsc70/auxilin complex: Substrate transfer and interdomain structural change

PubMed Central

Gruschus, James M.; Greene, Lois E.; Eisenberg, Evan; Ferretti, James A.

2004-01-01

A model structure of the Hsc70/auxilin complex has been constructed to gain insight into interprotein substrate transfer and ATP hydrolysis induced conformational changes in the multidomain Hsc70 structure. The Hsc70/auxilin system, which is a member of the Hsp70/Hsp40 chaperone system family, uncoats clathrin-coated vesicles in an ATP hydrolysis-driven process. Incorporating previous results from NMR and mutant binding studies, the auxilin J-domain was docked into the Hsc70 ATPase domain lower cleft using rigid backbone/flexible side chain molecular dynamics, and the Hsc70 substrate binding domain was docked by a similar procedure. For comparison, J-domain and substrate binding domain docking sites were obtained by the rigid-body docking programs DOT and ZDOCK, filtered and ranked by the program ClusPro, and relaxed using the same rigid backbone/flexible side chain dynamics. The substrate binding domain sites were assessed in terms of conserved surface complementarity and feasibility in the context of substrate transfer, both for auxilin and another Hsp40 protein, Hsc20. This assessment favors placement of the substrate binding domain near D152 on the ATPase domain surface adjacent to the J-domain invariant HPD segment, with the Hsc70 interdomain linker in the lower cleft. Examining Hsc70 interdomain energetics, we propose that long-range electrostatic interactions, perhaps due to a difference in the pKa values of bound ATP and ADP, could play a major role in the structural change induced by ATP hydrolysis. Interdomain electrostatic interactions also appear to play a role in stimulation of ATPase activity due to J-domain binding and substrate binding by Hsc70. PMID:15273304

Using Grand Canonical Monte Carlo Simulations to Understand the Role of Interfacial Fluctuations on Solvation at the Water-Vapor Interface.

PubMed

Rane, Kaustubh; van der Vegt, Nico F A

2016-09-15

The present work investigates the effect of interfacial fluctuations (predominantly capillary wave-like fluctuations) on the solvation free energy (Δμ) of a monatomic solute at the water-vapor interface. We introduce a grand-canonical-ensemble-based simulation approach that quantifies the contribution of interfacial fluctuations to Δμ. This approach is used to understand how the above contribution depends on the strength of dispersive and electrostatic solute-water interactions at the temperature of 400 K. At this temperature, we observe that interfacial fluctuations do play a role in the variation of Δμ with the strength of the electrostatic solute-water interaction. We also use grand canonical simulations to further investigate how interfacial fluctuations affect the propensity of the solute toward the water-vapor interface. To this end, we track a quantity called the interface potential (surface excess free energy) with the number of water molecules. With increasing number of water molecules, the liquid-vapor interface moves across a solute, which is kept at a fixed position in the simulation. Hence, the dependence of the interface potential on the number of waters models the process of moving the solute through the water-vapor interface. We analyze the change of the interface potential with the number of water molecules to explain that solute-induced changes in the interfacial fluctuations, like the pinning of capillary-wave-like undulations, do not play any role in the propensity of solutes toward water-vapor interfaces. The above analysis also shows that the dampening of interfacial fluctuations accompanies the adsorption of any solute at the liquid-vapor interface, irrespective of the chemical nature of the solute and solvent. However, such a correlation does not imply that dampening of fluctuations causes adsorption.

Polyelectrolytes and Their Biological Interactions

PubMed Central

Katchalsky, A.

1964-01-01

Polyelectrolytes are water-soluble electrically charged polymers. Their properties are determined by the interplay of the electrical forces, the Brownian motion of the macromolecular chain, and intermolecular Van der Waals forces. Charged polyacids or polybases are stretched by the electrostatic forces, as evidenced by increase in solution viscosity, or by the stretching of polyelectrolyte gels. The electrical field of the polyions is neutralized by a dense atmosphere of counter-ions. The counter-ion attraction to the polyions is expressed by a reduction of the osmotic activity of the polyion—the osmotic pressure being only 15 to 20 per cent of the ideal in highly charged polyelectrolytes neutralized by monovalent counter-ions, and as low as 1 to 3 per cent of the ideal for polyvalent counter-ions. Since the ionic atmosphere is only slightly dependent on added low molecular salt, the osmotic pressure of polyelectrolyte salt mixtures is approximately equal to the sum of the osmotic pressure of polyelectrolyte and salt alone. Acidic and basic polyelectrolytes interact electrostatically with precipitation at the point of polymeric electroneutrality. At higher salt concentrations the interaction is inhibited by the screening of polymeric fixed charges. The importance of these interactions in enzymatic processes is discussed. The electrical double layer is polarizable as may be deduced from dielectric and conductometric studies. The polarizability leads to strong dipole formation in an electrical field. These macromolecular dipoles may play a role in the adsorption of polyelectrolytes on charged surfaces. The final part of the paper is devoted to interactions of polyelectrolytes with cell membranes and the gluing of cells to higher aggregates by charged biocolloids. ImagesFigure 17Figure 18Figure 19Figure 20 PMID:14104085

Optimizing pH response of affinity between protein G and IgG Fc: how electrostatic modulations affect protein-protein interactions.

PubMed

Watanabe, Hideki; Matsumaru, Hiroyuki; Ooishi, Ayako; Feng, Yanwen; Odahara, Takayuki; Suto, Kyoko; Honda, Shinya

2009-05-01

Protein-protein interaction in response to environmental conditions enables sophisticated biological and biotechnological processes. Aiming toward the rational design of a pH-sensitive protein-protein interaction, we engineered pH-sensitive mutants of streptococcal protein G B1, a binder to the IgG constant region. We systematically introduced histidine residues into the binding interface to cause electrostatic repulsion on the basis of a rigid body model. Exquisite pH sensitivity of this interaction was confirmed by surface plasmon resonance and affinity chromatography employing a clinically used human IgG. The pH-sensitive mechanism of the interaction was analyzed and evaluated from kinetic, thermodynamic, and structural viewpoints. Histidine-mediated electrostatic repulsion resulted in significant loss of exothermic heat of the binding that decreased the affinity only at acidic conditions, thereby improving the pH sensitivity. The reduced binding energy was partly recovered by "enthalpy-entropy compensation." Crystal structures of the designed mutants confirmed the validity of the rigid body model on which the effective electrostatic repulsion was based. Moreover, our data suggested that the entropy gain involved exclusion of water molecules solvated in a space formed by the introduced histidine and adjacent tryptophan residue. Our findings concerning the mechanism of histidine-introduced interactions will provide a guideline for the rational design of pH-sensitive protein-protein recognition.

Role of electrostatic interaction on surfactant induced protein unfolding

NASA Astrophysics Data System (ADS)

Sumit, Kumar, Sugam; Aswal, V. K.

2013-02-01

Small Angle Neutron Scattering has been used to examine the effect of electrostatic interaction on surfactant induced protein unfolding. Measurements are carried out from 1 wt% Bovine Serum Albumin (BSA) protein with 1 wt% Sodium Dodecyl Sulphate (SDS) surfactant at pH 7 in presence of varying concentration of NaCl. It is found that both the components (protein and surfactant micelle which are likely charged) exist individually without any interaction in absence of salt, whereas their interaction and protein unfolding is enhanced with the increase in salt concentration. The structure of protein-surfactant interaction is characterized by fractal bead-necklace model.

Highly viscous antibody solutions are a consequence of network formation caused by domain-domain electrostatic complementarities: insights from coarse-grained simulations.

PubMed

Buck, Patrick M; Chaudhri, Anuj; Kumar, Sandeep; Singh, Satish K

2015-01-05

Therapeutic monoclonal antibody (mAb) candidates that form highly viscous solutions at concentrations above 100 mg/mL can lead to challenges in bioprocessing, formulation development, and subcutaneous drug delivery. Earlier studies of mAbs with concentration-dependent high viscosity have indicated that mAbs with negatively charged Fv regions have a dipole-like quality that increases the likelihood of reversible self-association. This suggests that weak electrostatic intermolecular interactions can form transient antibody networks that participate in resistance to solution deformation under shear stress. Here this hypothesis is explored by parametrizing a coarse-grained (CG) model of an antibody using the domain charges from four different mAbs that have had their concentration-dependent viscosity behaviors previously determined. Multicopy molecular dynamics simulations were performed for these four CG mAbs at several concentrations to understand the effect of surface charge on mass diffusivity, pairwise interactions, and electrostatic network formation. Diffusion coefficients computed from simulations were in qualitative agreement with experimentally determined viscosities for all four mAbs. Contact analysis revealed an overall greater number of pairwise interactions for the two mAbs in this study with high concentration viscosity issues. Further, using equilibrated solution trajectories, the two mAbs with high concentration viscosity issues quantitatively formed more features of an electrostatic network than the other mAbs. The change in the number of these network features as a function of concentration is related to the number of pairwise interactions formed by electrostatic complementarities between antibody domains. Thus, transient antibody network formation caused by domain-domain electrostatic complementarities is the most probable origin of high concentration viscosity for mAbs in this study.

Rational modification of protein stability by targeting surface sites leads to complicated results

PubMed Central

Xiao, Shifeng; Patsalo, Vadim; Shan, Bing; Bi, Yuan; Green, David F.; Raleigh, Daniel P.

2013-01-01

The rational modification of protein stability is an important goal of protein design. Protein surface electrostatic interactions are not evolutionarily optimized for stability and are an attractive target for the rational redesign of proteins. We show that surface charge mutants can exert stabilizing effects in distinct and unanticipated ways, including ones that are not predicted by existing methods, even when only solvent-exposed sites are targeted. Individual mutation of three solvent-exposed lysines in the villin headpiece subdomain significantly stabilizes the protein, but the mechanism of stabilization is very different in each case. One mutation destabilizes native-state electrostatic interactions but has a larger destabilizing effect on the denatured state, a second removes the desolvation penalty paid by the charged residue, whereas the third introduces unanticipated native-state interactions but does not alter electrostatics. Our results show that even seemingly intuitive mutations can exert their effects through unforeseen and complex interactions. PMID:23798426

Electrostatic interactions guide the active site face of a structure-specific ribonuclease to its RNA substrate.

PubMed

Plantinga, Matthew J; Korennykh, Alexei V; Piccirilli, Joseph A; Correll, Carl C

2008-08-26

Restrictocin, a member of the alpha-sarcin family of site-specific endoribonucleases, uses electrostatic interactions to bind to the ribosome and to RNA oligonucleotides, including the minimal specific substrate, the sarcin/ricin loop (SRL) of 23S-28S rRNA. Restrictocin binds to the SRL by forming a ground-state E:S complex that is stabilized predominantly by Coulomb interactions and depends on neither the sequence nor structure of the RNA, suggesting a nonspecific complex. The 22 cationic residues of restrictocin are dispersed throughout this protein surface, complicating a priori identification of a Coulomb interacting surface. Structural studies have identified an enzyme-substrate interface, which is expected to overlap with the electrostatic E:S interface. Here, we identified restrictocin residues that contribute to binding in the E:S complex by determining the salt dependence [partial differential log(k 2/ K 1/2)/ partial differential log[KCl

The role of electrostatics in protein-protein interactions of a monoclonal antibody.

PubMed

Roberts, D; Keeling, R; Tracka, M; van der Walle, C F; Uddin, S; Warwicker, J; Curtis, R

2014-07-07

Understanding how protein-protein interactions depend on the choice of buffer, salt, ionic strength, and pH is needed to have better control over protein solution behavior. Here, we have characterized the pH and ionic strength dependence of protein-protein interactions in terms of an interaction parameter kD obtained from dynamic light scattering and the osmotic second virial coefficient B22 measured by static light scattering. A simplified protein-protein interaction model based on a Baxter adhesive potential and an electric double layer force is used to separate out the contributions of longer-ranged electrostatic interactions from short-ranged attractive forces. The ionic strength dependence of protein-protein interactions for solutions at pH 6.5 and below can be accurately captured using a Deryaguin-Landau-Verwey-Overbeek (DLVO) potential to describe the double layer forces. In solutions at pH 9, attractive electrostatics occur over the ionic strength range of 5-275 mM. At intermediate pH values (7.25 to 8.5), there is a crossover effect characterized by a nonmonotonic ionic strength dependence of protein-protein interactions, which can be rationalized by the competing effects of long-ranged repulsive double layer forces at low ionic strength and a shorter ranged electrostatic attraction, which dominates above a critical ionic strength. The change of interactions from repulsive to attractive indicates a concomitant change in the angular dependence of protein-protein interaction from isotropic to anisotropic. In the second part of the paper, we show how the Baxter adhesive potential can be used to predict values of kD from fitting to B22 measurements, thus providing a molecular basis for the linear correlation between the two protein-protein interaction parameters.

A repertoire of pyridinium-phenyl-methyl cross-talk through a cascade of intramolecular electrostatic interactions.

PubMed

Acharya, P; Plashkevych, O; Morita, C; Yamada, S; Chattopadhyaya, J

2003-02-21

Direct intramolecular cation-pi interaction between phenyl and pyridinium moieties in 1a(+) has been experimentally evidenced through pH-dependent (1)H NMR titration. The basicity of the pyridinyl group (pK(a) 2.9) in 1a can be measured both from the pH-dependent chemical shifts of the pyridinyl protons as well as from the protons of the neighboring phenyl and methyl groups as a result of electrostatic interaction between the phenyl and the pyridinium ion in 1a(+) at the ground state. The net result of this nearest neighbor electrostatic interaction is that the pyridinium moiety in 1a becomes more basic (pK(a) 2.92) compared to that in the standard 2a (pK(a) 2.56) as a consequence of edge-to-face cation (pyridinium)-pi (phenyl) interaction, giving a free energy of stabilization (DeltaDeltaG(o)pKa) of -2.1 kJ mol(-1). The fact that the pH-dependent downfield shifts of the phenyl and methyl protons give the pK(a) of the pyridine moiety of 1a also suggests that the nearest neighbor cation (pyridinium)-pi (phenyl) interaction also steers the CH (methyl)-pi (phenyl) interaction in tandem. This means that the whole pyridine-phenyl-methyl system in 1a(+) is electronically coupled at the ground state, cross-modulating the physicochemical property of the next neighbor by using the electrostatics as the engine, and the origin of this electrostatics is a far away point in the molecule-the pyridinyl-nitrogen. The relative chemical shift changes and the pK(a) differences show that the cation (pyridinium)-pi (phenyl) interaction is indeed more stable (DeltaDeltaG(o)pKa = -2.1 kJ mol(-1)) than that of the CH (methyl)-pi (phenyl) interaction (DeltaDeltaG(o)pKa = -0.8 kJ mol(-1)). Since the pK(a) of the pyridine moiety in 1a is also obtained through the pH-dependent shifts of both phenyl and methyl protons, it suggests that the net electrostatic mediated charge transfer from the phenyl to the pyridinium and its effect on the CH (methyl)-pi (phenyl) interaction corresponds to DeltaG(o)pKa of the pyridinium ion (approximately 17.5 kJ mol(-1)), which means that the aromatic characters of the phenyl and the pyridinium rings in 1a(+) have been cross-modulated owing to the edge-to-face interaction proportional to this DeltaG(o)pKa change.

Adsorption of insulin peptide on charged single-walled carbon nanotubes: significant role of ordered water molecules.

PubMed

Shen, Jia-Wei; Wu, Tao; Wang, Qi; Kang, Yu; Chen, Xin

2009-06-02

Ordered hydration shells: The more ordered hydration shells outside the charged CNT surfaces prevent more compact adsorption of the peptide in the charged CNT systems [picture: see text], but peptide binding strengths on the charged CNT surfaces are stronger due to the electrostatic interaction.Studies of adsorption dynamics and stability for peptides/proteins on single-walled carbon nanotubes (SWNTs) are of great importance for a better understanding of the properties and nature of nanotube-based biosystems. Herein, the dynamics and mechanism of the adsorption of the insulin chain B peptide on different charged SWNTs are investigated by explicit solvent molecular dynamics simulations. The results show that all types of surfaces effectively attract the model peptide. Water molecules play a significant role in peptide adsorption on the surfaces of charged carbon nanotubes (CNTs). Compared to peptide adsorption on neutral CNT surfaces, the more ordered hydration shells outside the tube prevent more compact adsorption of the peptide in charged CNT systems. This shield effect leads to a smaller conformational change and van der Waals interaction between the peptide and surfaces, but peptide binding strengths on charged CNT surfaces are stronger than those on the neutral CNT surface due to the strong electrostatic interaction. The result of these simulations implies the possibility of improving the binding strength of peptides/proteins on CNT surfaces, as well as keeping the integrity of the peptide/protein conformation in peptide/protein-CNT complexes by charging the CNTs.

Size-controlled and redox-responsive supramolecular nanoparticles

PubMed Central

2015-01-01

Summary Control over the assembly and disassembly of nanoparticles is pivotal for their use as drug delivery vehicles. Here, we aim to form supramolecular nanoparticles (SNPs) by combining advantages of the reversible assembly properties of SNPs using host–guest interactions and of a stimulus-responsive moiety. The SNPs are composed of a core of positively charged poly(ethylene imine) grafted with β-cyclodextrin (CD) and a positively charged ferrocene (Fc)-terminated poly(amidoamine) dendrimer, with a monovalent stabilizer at the surface. Fc was chosen for its loss of CD-binding properties when oxidizing it to the ferrocenium cation. The ionic strength was shown to play an important role in controlling the aggregate growth. The attractive supramolecular and repulsive electrostatic interactions constitute a balance of forces in this system at low ionic strengths. At higher ionic strengths, the increased charge screening led to a loss of electrostatic repulsion and therefore to faster aggregate growth. A Job plot showed that a 1:1 stoichiometry of host and guest moieties gave the most efficient aggregate growth. Different stabilizers were used to find the optimal stopper to limit the growth. A weaker guest moiety was shown to be less efficient in stabilizing the SNPs. Also steric repulsion is important for achieving SNP stability. SNPs of controlled particle size and good stability (up to seven days) were prepared by fine-tuning the ratio of multivalent and monovalent interactions. Finally, reversibility of the SNPs was confirmed by oxidizing the Fc guest moieties in the core of the SNPs. PMID:26733345

Unveiling the stimulatory effects of tartrazine on human and bovine serum albumin fibrillogenesis: Spectroscopic and microscopic study

NASA Astrophysics Data System (ADS)

Al-Shabib, Nasser Abdulatif; Khan, Javed Masood; Alsenaidy, Mohammad A.; Alsenaidy, Abdulrahman M.; Khan, Mohd Shahnawaz; Husain, Fohad Mabood; Khan, Mohammad Rashid; Naseem, Mohammad; Sen, Priyankar; Alam, Parvez; Khan, Rizwan Hasan

2018-02-01

Amyloid fibrils are playing key role in the pathogenesis of various neurodegenerative diseases. Generally anionic molecules are known to induce amyloid fibril in several proteins. In this work, we have studied the effect of anionic food additive dye i.e., tartrazine (TZ) on the amyloid fibril formation of human serum albumins (HSA) and bovine serum albumin (BSA) at pHs 7.4 and 3.5. We have employed various biophysical methods like, turbidity measurements, Rayleigh Light Scattering (RLS), Dynamic Light Scattering (DLS), intrinsic fluorescence, Congo red assay, far-UV CD, transmission electron microscopy (TEM) and atomic force microscopy (AFM) to decipher the mechanism of TZ-induce amyloid fibril formation in both the serum albumins at pHs 7.4 and 3.5. The obtained results suggest that both the albumins forms amyloid-like aggregates in the presence of 1.0 to 15.0 mM of TZ at pH 3.5, but no amyloid fibril were seen at pH 7.4. The possible cause of TZ-induced amyloid fibril formation is electrostatic and hydrophobic interaction because sulfate group of TZ may have interacted electrostatically with positively charged amino acids of the albumins at pH 3.5 and increased protein-protein and protein-TZ interactions leading to amyloid fibril formation. The TEM, RLS and DLS results are suggesting that BSA forms bigger size amyloids compared to HSA, may be due to high surface hydrophobicity of BSA.

Electrostatic complementarity at protein/protein interfaces.

PubMed

McCoy, A J; Chandana Epa, V; Colman, P M

1997-05-02

Calculation of the electrostatic potential of protein-protein complexes has led to the general assertion that protein-protein interfaces display "charge complementarity" and "electrostatic complementarity". In this study, quantitative measures for these two terms are developed and used to investigate protein-protein interfaces in a rigorous manner. Charge complementarity (CC) was defined using the correlation of charges on nearest neighbour atoms at the interface. All 12 protein-protein interfaces studied had insignificantly small CC values. Therefore, the term charge complementarity is not appropriate for the description of protein-protein interfaces when used in the sense measured by CC. Electrostatic complementarity (EC) was defined using the correlation of surface electrostatic potential at protein-protein interfaces. All twelve protein-protein interfaces studied had significant EC values, and thus the assertion that protein-protein association involves surfaces with complementary electrostatic potential was substantially confirmed. The term electrostatic complementarity can therefore be used to describe protein-protein interfaces when used in the sense measured by EC. Taken together, the results for CC and EC demonstrate the relevance of the long-range effects of charges, as described by the electrostatic potential at the binding interface. The EC value did not partition the complexes by type such as antigen-antibody and proteinase-inhibitor, as measures of the geometrical complementarity at protein-protein interfaces have done. The EC value was also not directly related to the number of salt bridges in the interface, and neutralisation of these salt bridges showed that other charges also contributed significantly to electrostatic complementarity and electrostatic interactions between the proteins. Electrostatic complementarity as defined by EC was extended to investigate the electrostatic similarity at the surface of influenza virus neuraminidase where the epitopes of two monoclonal antibodies, NC10 and NC41, overlap. Although NC10 and NC41 both have quite high values of EC for their interaction with neuraminidase, the similarity in electrostatic potential generated by the two on the overlapping region of the epitopes is insignificant. Thus, it is possible for two antibodies to recognise the electrostatic surface of a protein in dissimilar ways.

Thermodynamics of binding interactions between extracellular polymeric substances and heavy metals by isothermal titration microcalorimetry.

PubMed

Yan, Peng; Xia, Jia-Shuai; Chen, You-Peng; Liu, Zhi-Ping; Guo, Jin-Song; Shen, Yu; Zhang, Cheng-Cheng; Wang, Jing

2017-05-01

Extracellular polymeric substances (EPS) play a crucial role in heavy metal bio-adsorption using activated sludge, but the interaction mechanism between heavy metals and EPS remains unclear. Isothermal titration calorimetry was employed to illuminate the mechanism in this study. The results indicate that binding between heavy metals and EPS is spontaneous and driven mainly by enthalpy change. Extracellular proteins in EPS are major participants in the binding process. Environmental conditions have significant impact on the adsorption performance. Divalent and trivalent cations severely impeded the binding of heavy metal ions to EPS. Electrostatic interaction mainly attributed to competition between divalent cations and heavy metal ions; trivalent cations directly competed with heavy metal ions for EPS binding sites. Trivalent cations were more competitive than divalent cations for heavy metal ion binding because they formed complexing bonds. This study facilitates a better understanding about the interaction between heavy metals and EPS in wastewater treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

The interaction of C.I. acid red 27 with human hemoglobin in solution.

PubMed

Wang, Yan-Qing; Zhang, Hong-Mei; Tang, Bo-Ping

2010-08-02

The nature of the interaction between human hemoglobin and C.I. acid red 27 was investigated systematically by ultraviolet-vis absorbance, circular dichroism, fluorescence, synchronous fluorescence, and three-dimensional fluorescence spectra techniques at pH 7.40. The quenching mechanism, binding constants, and the number of binding sites were determined by the quenching of human hemoglobin fluorescence in presence of C.I. acid red 27. The results showed that the nature of the quenching was of static type and the process of binding acid red 27 on human hemoglobin was a spontaneous molecular interaction procedure. The electrostatic and hydrophobic interactions played a major role in stabilizing the complex; The distance r between donor and acceptor was obtained to be 4.40 nm according to Förster's theory; The effect of acid red 27 on the conformation of human hemoglobin was analyzed using synchronous fluorescence, circular dichroism and three-dimensional fluorescence spectra. 2010 Elsevier B.V. All rights reserved.

Interaction between Pin1 and its natural product inhibitor epigallocatechin-3-gallate by spectroscopy and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Xi, Lei; Wang, Yu; He, Qing; Zhang, Qingyan; Du, Linfang

2016-12-01

The binding of epigallocatechin-3-gallate (EGCG) to wild type Pin1 in solution was studied by spectroscopic methods and molecular dynamics simulations in this research to explore the binding mode and inhibition mechanism. The binding constants and number of binding sites per Pin1 for EGCG were calculated through the Stern-Volmer equation. The values of binding free energy and thermodynamic parameters were calculated and indicated that hydrogen bonds, electrostatic interaction and Van der Waals interaction played the major role in the binding process. The alterations of Pin1 secondary structure in the presence of EGCG were confirmed by far-UV circular dichroism spectra. The binding model at atomic-level revealed that EGCG was bound to the Glu12, Lys13, Arg14, Met15 and Arg17 in WW domain. Furthermore, EGCG could also interact with Arg69, Asp112, Cys113 and Ser114 in PPIase domain.

Prediction of Protein-Protein Interaction Sites Using Electrostatic Desolvation Profiles

PubMed Central

Fiorucci, Sébastien; Zacharias, Martin

2010-01-01

Abstract Protein-protein complex formation involves removal of water from the interface region. Surface regions with a small free energy penalty for water removal or desolvation may correspond to preferred interaction sites. A method to calculate the electrostatic free energy of placing a neutral low-dielectric probe at various protein surface positions has been designed and applied to characterize putative interaction sites. Based on solutions of the finite-difference Poisson equation, this method also includes long-range electrostatic contributions and the protein solvent boundary shape in contrast to accessible-surface-area-based solvation energies. Calculations on a large set of proteins indicate that in many cases (>90%), the known binding site overlaps with one of the six regions of lowest electrostatic desolvation penalty (overlap with the lowest desolvation region for 48% of proteins). Since the onset of electrostatic desolvation occurs even before direct protein-protein contact formation, it may help guide proteins toward the binding region in the final stage of complex formation. It is interesting that the probe desolvation properties associated with residue types were found to depend to some degree on whether the residue was outside of or part of a binding site. The probe desolvation penalty was on average smaller if the residue was part of a binding site compared to other surface locations. Applications to several antigen-antibody complexes demonstrated that the approach might be useful not only to predict protein interaction sites in general but to map potential antigenic epitopes on protein surfaces. PMID:20441756

Effect of the ordered interfacial water layer in protein complex formation: a non-local electrostatic approach

NASA Astrophysics Data System (ADS)

Rubinstein, Alexander; Sabirianov, Renat

2011-03-01

Using a non-local electrostatic approach that incorporates the short-range structure of the contacting media, we evaluated the electrostatic contribution to the energy of the complex formation of two model proteins. In this study, we have demonstrated that the existence of an low-dielectric interfacial water layer at the protein-solvent interface reduces the charging energy of the proteins in the aqueous solvent, and consequently increases the electrostatic contribution to the protein binding (change in free energy upon the complex formation of two proteins). This is in contrast with the finding of the continuum electrostatic model, which suggests that electrostatic interactions are not strong enough to compensate for the unfavorable desolvation effects.

Model lipid bilayers mimic non-specific interactions of gold nanoparticles with macrophage plasma membranes.

PubMed

Montis, Costanza; Generini, Viola; Boccalini, Giulia; Bergese, Paolo; Bani, Daniele; Berti, Debora

2018-04-15

Understanding the interaction between nanomaterials and biological interfaces is a key unmet goal that still hampers clinical translation of nanomedicine. Here we investigate and compare non-specific interaction of gold nanoparticles (AuNPs) with synthetic lipid and wild type macrophage membranes. A comprehensive data set was generated by systematically varying the structural and physicochemical properties of the AuNPs (size, shape, charge, surface functionalization) and of the synthetic membranes (composition, fluidity, bending properties and surface charge), which allowed to unveil the matching conditions for the interaction of the AuNPs with macrophage plasma membranes in vitro. This effort directly proved for the first time that synthetic bilayers can be set to mimic and predict with high fidelity key aspects of nanoparticle interaction with macrophage eukaryotic plasma membranes. It then allowed to model the experimental observations according to classical interface thermodynamics and in turn determine the paramount role played by non-specific contributions, primarily electrostatic, Van der Waals and bending energy, in driving nanoparticle-plasma membrane interactions. Copyright © 2018 Elsevier Inc. All rights reserved.

PIP2-dependent coupling is prominent in Kv7.1 due to weakened interactions between S4-S5 and S6

NASA Astrophysics Data System (ADS)

Kasimova, Marina A.; Zaydman, Mark A.; Cui, Jianmin; Tarek, Mounir

2015-01-01

Among critical aspects of voltage-gated potassium (Kv) channels' functioning is the effective communication between their two composing domains, the voltage sensor (VSD) and the pore. This communication, called coupling, might be transmitted directly through interactions between these domains and, as recently proposed, indirectly through interactions with phosphatidylinositol-4,5-bisphosphate (PIP2), a minor lipid of the inner plasma membrane leaflet. Here, we show how the two components of coupling, mediated by protein-protein or protein-lipid interactions, both contribute in the Kv7.1 functioning. On the one hand, using molecular dynamics simulations, we identified a Kv7.1 PIP2 binding site that involves residues playing a key role in PIP2-dependent coupling. On the other hand, combined theoretical and experimental approaches have shown that the direct interaction between the segments of the VSD (S4-S5) and the pore (S6) is weakened by electrostatic repulsion. Finally, we conclude that due to weakened protein-protein interactions, the PIP2-dependent coupling is especially prominent in Kv7.1.

Electrostatic Functionalization and Passivation of Water-Exfoliated Few-Layer Black Phosphorus by Poly Dimethyldiallyl Ammonium Chloride and Its Ultrafast Laser Application.

PubMed

Feng, Qingliang; Liu, Hongyan; Zhu, Meijie; Shang, Jing; Liu, Dan; Cui, Xiaoqi; Shen, Diqin; Kou, Liangzhi; Mao, Dong; Zheng, Jianbang; Li, Chun; Zhang, Jin; Xu, Hua; Zhao, Jianlin

2018-03-21

Few-layer black phosphorus (BP) which exhibits excellent optical and electronic properties, has great potential applications in nanodevices. However, BP inevitably suffers from the rapid degradation in ambient air because of the high reactivity of P atoms with oxygen and water, which greatly hinders its wide applications. Herein, we demonstrate the electrostatic functionalization as an effective way to simultaneously enhance the stability and dispersity of aqueous phase exfoliated few-layer BP. The poly dimethyldiallyl ammonium chloride (PDDA) is selected to spontaneously and uniformly adsorb on the surface of few-layer BP via electrostatic interaction. The positive charge-center of the N atom of PDDA, which passivates the lone-pair electrons of P, plays a critical role in stabilizing the BP. Meanwhile, the PDDA could serve as hydrophilic ligands to improve the dispersity of exfoliated BP in water. The thinner PDDA-BP nanosheets can stabilize in both air and water even after 15 days of exposure. Finally, the uniform PDDA-BP-polymer film was used as a saturable absorber to realize passive mode-locking operations in a fiber laser, delivering a train of ultrafast pulses with the duration of 1.2 ps at 1557.8 nm. This work provides a new way to obtain highly stable few-layer BP, which shows great promise in ultrafast optics application.

Lack of Dependence of the Sizes of the Mesoscopic Protein Clusters on Electrostatics.

PubMed

Vorontsova, Maria A; Chan, Ho Yin; Lubchenko, Vassiliy; Vekilov, Peter G

2015-11-03

Protein-rich clusters of steady submicron size and narrow size distribution exist in protein solutions in apparent violation of the classical laws of phase equilibrium. Even though they contain a minor fraction of the total protein, evidence suggests that they may serve as essential precursors for the nucleation of ordered solids such as crystals, sickle-cell hemoglobin polymers, and amyloid fibrils. The cluster formation mechanism remains elusive. We use the highly basic protein lysozyme at nearly neutral and lower pH as a model and explore the response of the cluster population to the electrostatic forces, which govern numerous biophysical phenomena, including crystallization and fibrillization. We tune the strength of intermolecular electrostatic forces by varying the solution ionic strength I and pH and find that despite the weaker repulsion at higher I and pH, the cluster size remains constant. Cluster responses to the presence of urea and ethanol demonstrate that cluster formation is controlled by hydrophobic interactions between the peptide backbones, exposed to the solvent after partial protein unfolding that may lead to transient protein oligomers. These findings reveal that the mechanism of the mesoscopic clusters is fundamentally different from those underlying the two main classes of ordered protein solid phases, crystals and amyloid fibrils, and partial unfolding of the protein chain may play a significant role. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Tuning calcite morphology and growth acceleration by a rational design of highly stable protein-mimetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Chunlong; Qi, Jiahui; Tao, Jinhui

2014-09-05

In nature, proteins play a significant role in biomineral formation. One of the ultimate goals of bioinspired materials science is to develop highly stable synthetic molecules that mimic the function of these natural proteins by controlling crystal formation. Here, we demonstrate that both the morphology and the degree of acceleration or inhibition observed during growth of calcite in the presence of peptoids can be rationally tuned by balancing the electrostatic interactions (EI) and hydrophobic interactions (HI), with HI playing the dominant role. While either strong EI or HI inhibit growth and suppress (104) face expression, correlations between peptoid-crystal binding energiesmore » and observed changes in calcite growth indicate moderate EI allow peptoids to weakly adsorb while moderate HI cause disruption of surface-adsorbed water layers, leading to growth acceleration with retained expression of (104) faces. This study provides fundamental principles for designing peptoids as crystallization promoters, and offers a straightforward screening method based on macroscopic crystal morphology. Because peptoids are sequence-specific, highly stable, and easily synthesized, peptoid-enhanced crystallization offers a broad range of potential applications.« less

Carbene-aerogen bonds: an ab initio study

NASA Astrophysics Data System (ADS)

Esrafili, Mehdi D.; Sabouri, Ayda

2017-04-01

Through the use of ab initio calculations, the possibility of formation of σ-hole interaction between ZO3 (Z = Ar, Kr and Xe) and carbene species is investigated. Since singlet carbenes show a negative electrostatic potential on their divalent carbon atom, they can favourably interact with the positive electrostatic potential generated by the σ-hole of Z atom of ZO3. The characteristic of this interaction, termed as 'carbene-aerogen' bond, is analysed in terms of geometric, interaction energies and electronic features. The energy decomposition analysis indicates that for all complexes analysed here, the electrostatic energy is more negative than the polarisation or dispersion energy term. According to the electron density analysis, some partial covalent character can be ascribed to XeṡṡṡC interactions. In addition, the carbene-aerogen bond exhibits cooperative effects with the HṡṡṡO hydrogen-bonding interaction in ternary complexes where both interactions coexist. For a given carbene, the amount of these cooperative effects increases with the size of the Z atom. The results obtained in this work may be helpful for the extension and future application of σ-hole intermolecular interactions as well as coordination chemistry.

The thiocyanate anion is a primary driver of carbon dioxide capture by ionic liquids

NASA Astrophysics Data System (ADS)

Chaban, Vitaly

2015-01-01

Carbon dioxide, CO2, capture by room-temperature ionic liquids (RTILs) is a vivid research area featuring both accomplishments and frustrations. This work employs the PM7-MD method to simulate adsorption of CO2 by 1,3-dimethylimidazolium thiocyanate at 300 K. The obtained result evidences that the thiocyanate anion plays a key role in gas capture, whereas the impact of the 1,3-dimethylimidazolium cation is mediocre. Decomposition of the computed wave function on the individual molecular orbitals confirms that CO2-SCN binding extends beyond just expected electrostatic interactions in the ion-molecular system and involves partial sharing of valence orbitals.

Electrostatic interaction between stereocilia: I. Its role in supporting the structure of the hair bundle.

PubMed

Dolgobrodov, S G; Lukashkin, A N; Russell, I J

2000-12-01

This paper provides theoretical estimates for the forces of electrostatic interaction between adjacent stereocilia in auditory and vestibular hair cells. Estimates are given for parameters within the measured physiological range using constraints appropriate for the known geometry of the hair bundle. Stereocilia are assumed to possess an extended, negatively charged surface coat, the glycocalyx. Different charge distribution profiles within the glycocalyx are analysed. It is shown that charged glycocalices on the apical surface of the hair cells can support spatial separation between adjacent stereocilia in the hair bundles through electrostatic repulsion between stereocilia. The charge density profile within the glycocalyx is a crucial parameter. In fact, attraction instead of repulsion between adjacent stereocilia will be observed if the charge of the glycocalyx is concentrated near the membrane of the stereocilia, thereby making this type of charge distribution unlikely. The forces of electrostatic interaction between stereocilia may influence the mechanical properties of the hair bundle and, being strongly non-linear, contribute to the non-linear phenomena that have been recorded from the periphery of the auditory and vestibular systems.

Spectroscopic investigation of the effect of salt on binding of tartrazine with two homologous serum albumins: quantification by use of the Debye-Hückel limiting law and observation of enthalpy-entropy compensation.

PubMed

Bolel, Priyanka; Datta, Shubhashis; Mahapatra, Niharendu; Halder, Mintu

2012-08-30

Formation of ion pair between charged molecule and protein can lead to interesting biochemical phenomena. We report the evolution of thermodynamics of the binding of tartrazine, a negatively charged azo colorant, and serum albumins with salt. The dye binds predominantly electrostatically in low buffer strengths; however, on increasing salt concentration, affinity decreases considerably. The calculated thermodynamic parameters in high salt indicate manifestation of nonelectrostatic interactions, namely, van der Waals force and hydrogen bonding. Site-marker competitive binding studies and docking simulations indicate that the dye binds with HSA in the warfarin site and with BSA at the interface of warfarin and ibuprofen binding sites. The docked poses indicate nearby amino acid positive side chains, which are possibly responsible for electrostatic interaction. Using the Debye-Hückel interionic attraction theory for binding equilibria, it is shown that, for electrostatic binding the calculated free energy change increases linearly with square root of ionic strength. Also UV-vis, fluorescence, CD data indicate a decrease of interaction with salt concentration. This study quantitatively relates how ionic strength modulates the strength of the protein-ligand electrostatic interaction. The binding enthalpy and entropy have been found to compensate one another. The enthalpy-entropy compensation (EEC), general property of weak intermolecular interactions, has been discussed.

Role of electric fields in the MHD evolution of the kink instability

DOE PAGES

Lapenta, Giovanni; Skender, Marina

2017-02-17

Here, the discovery of electrostatic fields playing a crucial role in establishing plasma motion in the flux conversion and dynamo processes in reversed field pinches is revisited. In order to further elucidate the role of the electrostatic fields, a flux rope configuration susceptible to the kink instability is numerically studied with anMHDcode. Simulated nonlinear evolution of the kink instability is found to confirm the crucial role of the electrostatic fields. Anew insight is gained on the special function of the electrostatic fields: they lead the plasma towards the reconnection site at the mode resonant surface. Without this step the plasmamore » column could not relax to its nonlinear state, since no other agent is present to perform this role. While the inductive field generated directly by the kink instability is the dominant flow driver, the electrostatic field is found to allow the motion in the vicinity of the reconnection region.« less

Role of electric fields in the MHD evolution of the kink instability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lapenta, Giovanni; Skender, Marina

Here, the discovery of electrostatic fields playing a crucial role in establishing plasma motion in the flux conversion and dynamo processes in reversed field pinches is revisited. In order to further elucidate the role of the electrostatic fields, a flux rope configuration susceptible to the kink instability is numerically studied with anMHDcode. Simulated nonlinear evolution of the kink instability is found to confirm the crucial role of the electrostatic fields. Anew insight is gained on the special function of the electrostatic fields: they lead the plasma towards the reconnection site at the mode resonant surface. Without this step the plasmamore » column could not relax to its nonlinear state, since no other agent is present to perform this role. While the inductive field generated directly by the kink instability is the dominant flow driver, the electrostatic field is found to allow the motion in the vicinity of the reconnection region.« less

Ligand solvation in molecular docking.

PubMed

Shoichet, B K; Leach, A R; Kuntz, I D

1999-01-01

Solvation plays an important role in ligand-protein association and has a strong impact on comparisons of binding energies for dissimilar molecules. When databases of such molecules are screened for complementarity to receptors of known structure, as often occurs in structure-based inhibitor discovery, failure to consider ligand solvation often leads to putative ligands that are too highly charged or too large. To correct for the different charge states and sizes of the ligands, we calculated electrostatic and non-polar solvation free energies for molecules in a widely used molecular database, the Available Chemicals Directory (ACD). A modified Born equation treatment was used to calculate the electrostatic component of ligand solvation. The non-polar component of ligand solvation was calculated based on the surface area of the ligand and parameters derived from the hydration energies of apolar ligands. These solvation energies were subtracted from the ligand-receptor interaction energies. We tested the usefulness of these corrections by screening the ACD for molecules that complemented three proteins of known structure, using a molecular docking program. Correcting for ligand solvation improved the rankings of known ligands and discriminated against molecules with inappropriate charge states and sizes.

Short peptide-directed synthesis of one-dimensional platinum nanostructures with controllable morphologies

PubMed Central

Tao, Kai; Wang, Jiqian; Li, Yanpeng; Xia, Daohong; Shan, Honghong; Xu, Hai; Lu, Jian R.

2013-01-01

Although one dimensional (1D) Pt nanostructures with well-defined sizes and shapes have fascinating physiochemical properties, their preparation remains a great challenge. Here we report an easy and novel synthesis of 1D Pt nanostructures with controllable morphologies, through the combination of designer self-assembling I3K and phage-displayed P7A peptides. The nanofibrils formed via I3K self-assembly acted as template. Pt precursors ((PtCl4)2− and (PtCl6)2−) were immobilized by electrostatic interaction on the positively charged template surface and subsequent reduction led to the formation of 1D Pt nanostructures. P7A was applied to tune the continuity of the Pt nanostructures. Here, the electrostatic repulsion between the deprotonated C-terminal carboxyl groups of P7A molecules was demonstrated to play a key role. We finally showed that continuous and ordered 1D Pt morphology had a significantly improved electrochemical performance for the hydrogen and methanol electro-oxidation in comparison with either 1D discrete Pt nanoparticle assemblies or isolated Pt nanoparticles. PMID:23995118

Electrostatic and hydrodynamics effects in a sedimented magnetorheological suspension.

PubMed

Domínguez-García, P; Pastor, J M; Melle, Sonia; Rubio, Miguel A

2009-08-01

We present experimental results on the equilibrium microstructure of a sedimented magnetorheological suspension, namely, an aqueous suspension of micron-sized superparamagnetic particles. We develop a study of the electrical interactions on the suspension by processing video-microscopy images of the sedimented particles. We calculate the pair distribution function, g(r), which yields the electrostatic pair potential u(r), showing an anomalous attractive interaction for distances on the order of twice the particle diameter, with characteristic parameters whose values show a dependence with the two-dimensional concentration of particles. The repulsive body of the potential is adjusted to a DLVO expression in order to calculate the Debye screening length and the effective surface charge density. Influence of confinement and variations on the Boltzmann sedimentation profile because of the electrostatic interactions appear to be essential for the interpretation of experimental results.

The role of particle-to-cell interactions in dictating nanoparticle aided magnetophoretic separation of microalgal cells.

PubMed

Toh, Pey Yi; Ng, Bee Wah; Ahmad, Abdul Latif; Chieh, Derek Chan Juinn; Lim, JitKang

2014-11-07

Successful application of a magnetophoretic separation technique for harvesting biological cells often relies on the need to tag the cells with magnetic nanoparticles. This study investigates the underlying principle behind the attachment of iron oxide nanoparticles (IONPs) onto microalgal cells, Chlorella sp. and Nannochloropsis sp., in both freshwater and seawater, by taking into account the contributions of various colloidal forces involved. The complex interplay between van der Waals (vdW), electrostatic (ES) and Lewis acid-base interactions (AB) in dictating IONP attachment was studied under the framework of extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) analysis. Our results showed that ES interaction plays an important role in determining the net interaction between the Chlorella sp. cells and IONPs in freshwater, while the AB and vdW interactions play a more dominant role in dictating the net particle-to-cell interaction in high ionic strength media (≥100 mM NaCl), such as seawater. XDLVO predicted effective attachment between cells and surface functionalized IONPs (SF-IONPs) with an estimated secondary minimum of -3.12 kT in freshwater. This prediction is in accordance with the experimental observation in which 98.89% of cells can be magnetophoretically separated from freshwater with SF-IONPs. We have observed successful magnetophoretic separation of microalgal cells from freshwater and/or seawater for all the cases as long as XDLVO analysis predicts particle attachment. For both the conditions, no pH adjustment is required for particle-to-cell attachment.

Grain-grain interaction in stationary dusty plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lampe, Martin; Joyce, Glenn

We present a particle-in-cell simulation study of the steady-state interaction between two stationary dust grains in uniform stationary plasma. Both the electrostatic force and the shadowing force on the grains are calculated explicitly. The electrostatic force is always repulsive. For two grains of the same size, the electrostatic force is very nearly equal to the shielded electric field due to a single isolated grain, acting on the charge of the other grain. For two grains of unequal size, the electrostatic force on the smaller grain is smaller than the isolated-grain field, and the force on the larger grain is largermore » than the isolated-grain field. In all cases, the attractive shadowing force exceeds the repulsive electrostatic force when the grain separation d is greater than an equilibrium separation d{sub 0}. d{sub 0} is found to be between 6λ{sub D} and 9λ{sub D} in all cases. The binding energy is estimated to be between 19 eV and 900 eV for various cases.« less

Kinesin motor protein as an electrostatic ratchet machine

NASA Astrophysics Data System (ADS)

Tsironis, George; Ciudad, Aleix; Sancho, Jose Maria

2008-03-01

Kinesin and related motor proteins utilize ATP fuel to propel themselves along the external surface of microtubules in a processive and directional fashion. We show that the observed step-like motion is possible through time varying charge distributions furnished by the ATP hydrolysis circle while the static charge configuration on the microtuble provides the guide for motion. Thus, while the chemical hydrolysis energy induces appropriate local conformational changes, the motor translational energy is fundamentally electrostatic. Numerical simulations of the mechanical equations of motion show that processivity and directionality are direct consequences of the ATP-dependent electrostatic interaction between the different charge distributions of kinesin and microtubule. Treating proterins as continuous dielectric media and using a Green's function formalism we find analytical expressions for the electrostatic energy in the vicinity of the protein surfaces. We calculate the Bjerrum length in the interior of the protein and analyze its dependence on the charge proximity to the protein interface. We apply these results to kinesin and estimate the pure electrostatic ATP-ADP interaction to be larger than 2k T.

Correlating Nitrile IR Frequencies to Local Electrostatics Quantifies Noncovalent Interactions of Peptides and Proteins.

PubMed

Deb, Pranab; Haldar, Tapas; Kashid, Somnath M; Banerjee, Subhrashis; Chakrabarty, Suman; Bagchi, Sayan

2016-05-05

Noncovalent interactions, in particular the hydrogen bonds and nonspecific long-range electrostatic interactions are fundamental to biomolecular functions. A molecular understanding of the local electrostatic environment, consistently for both specific (hydrogen-bonding) and nonspecific electrostatic (local polarity) interactions, is essential for a detailed understanding of these processes. Vibrational Stark Effect (VSE) has proven to be an extremely useful method to measure the local electric field using infrared spectroscopy of carbonyl and nitrile based probes. The nitrile chemical group would be an ideal choice because of its absorption in an infrared spectral window transparent to biomolecules, ease of site-specific incorporation into proteins, and common occurrence as a substituent in various drug molecules. However, the inability of VSE to describe the dependence of IR frequency on electric field for hydrogen-bonded nitriles to date has severely limited nitrile's utility to probe the noncovalent interactions. In this work, using infrared spectroscopy and atomistic molecular dynamics simulations, we have reported for the first time a linear correlation between nitrile frequencies and electric fields in a wide range of hydrogen-bonding environments that may bridge the existing gap between VSE and H-bonding interactions. We have demonstrated the robustness of this field-frequency correlation for both aromatic nitriles and sulfur-based nitriles in a wide range of molecules of varying size and compactness, including small molecules in complex solvation environments, an amino acid, disordered peptides, and structured proteins. This correlation, when coupled to VSE, can be used to quantify noncovalent interactions, specific or nonspecific, in a consistent manner.

Electrostatic screening in classical Coulomb fluids: exponential or power-law decay or both? An investigation into the effect of dispersion interactions

NASA Astrophysics Data System (ADS)

Kjellander, Roland

2006-04-01

It is shown that the nature of the non-electrostatic part of the pair interaction potential in classical Coulomb fluids can have a profound influence on the screening behaviour. Two cases are compared: (i) when the non-electrostatic part equals an arbitrary finite-ranged interaction and (ii) when a dispersion r-6 interaction potential is included. A formal analysis is done in exact statistical mechanics, including an investigation of the bridge function. It is found that the Coulombic r-1 and the dispersion r-6 potentials are coupled in a very intricate manner as regards the screening behaviour. The classical one-component plasma (OCP) is a particularly clear example due to its simplicity and is investigated in detail. When the dispersion r-6 potential is turned on, the screened electrostatic potential from a particle goes from a monotonic exponential decay, exp(-κr)/r, to a power-law decay, r-8, for large r. The pair distribution function acquire, at the same time, an r-10 decay for large r instead of the exponential one. There still remains exponentially decaying contributions to both functions, but these contributions turn oscillatory when the r-6 interaction is switched on. When the Coulomb interaction is turned off but the dispersion r-6 pair potential is kept, the decay of the pair distribution function for large r goes over from the r-10 to an r-6 behaviour, which is the normal one for fluids of electroneutral particles with dispersion interactions. Differences and similarities compared to binary electrolytes are pointed out.

TEMPO Monolayers on Si(100) Electrodes: Electrostatic Effects by the Electrolyte and Semiconductor Space-Charge on the Electroactivity of a Persistent Radical.

PubMed

Zhang, Long; Vogel, Yan Boris; Noble, Benjamin B; Gonçales, Vinicius R; Darwish, Nadim; Brun, Anton Le; Gooding, J Justin; Wallace, Gordon G; Coote, Michelle L; Ciampi, Simone

2016-08-03

This work demonstrates the effect of electrostatic interactions on the electroactivity of a persistent organic free radical. This was achieved by chemisorption of molecules of 4-azido-2,2,6,6-tetramethyl-1-piperdinyloxy (4-azido-TEMPO) onto monolayer-modified Si(100) electrodes using a two-step chemical procedure to preserve the open-shell state and hence the electroactivity of the nitroxide radical. Kinetic and thermodynamic parameters for the surface electrochemical reaction are investigated experimentally and analyzed with the aid of electrochemical digital simulations and quantum-chemical calculations of a theoretical model of the tethered TEMPO system. Interactions between the electrolyte anions and the TEMPO grafted on highly doped, i.e., metallic, electrodes can be tuned to predictably manipulate the oxidizing power of surface nitroxide/oxoammonium redox couple, hence showing the practical importance of the electrostatics on the electrolyte side of the radical monolayer. Conversely, for monolayers prepared on the poorly doped electrodes, the electrostatic interactions between the tethered TEMPO units and the semiconductor-side, i.e., space-charge, become dominant and result in drastic kinetic changes to the electroactivity of the radical monolayer as well as electrochemical nonidealities that can be explained as an increase in the self-interaction "a" parameter that leads to the Frumkin isotherm.

Forces between Two Glass Surfaces with Adsorbed Hexadecyltrimethylammonium Salicylate.

PubMed

Imae, T; Kato, M; Rutland, M

2000-02-22

Forces have been measured for hexadecyltrimethylammonium salicylate (C(16)TASal) layers on glass beads. During the inward process, hydrophobic attraction occurred at lower adsorption of C(16)TASal and electrostatic repulsion interactions happened at higher adsorption. While the jump-in phenomenon was observed for solutions of concentrations below the critical micelle concentration (cmc = 0.15 mM), the step-in phenomenon was characteristic for solutions at the cmc and above the cmc, suggesting the push-out of adsorbed C(16)TASal layers and/or inserted micelles. The remarkable pull-off phenomenon on the outward process occurred for all solutions, indicating a strong interaction between C(16)TASal molecules. For aqueous 0.15 mM C(16)TASal solutions of various NaSal concentrations, on the inward process, the electrostatic repulsive interaction decreased with adding NaSal. This is due to the electrostatic shielding by salt excess. The height of the force wall on the inward process reached a maximum at 0.01 M NaSal, but the interlocking between molecules on two surfaces during the outward process was minimized at 0.1 M NaSal. These tendencies, which are different from that of the electrostatic repulsion interaction, imply the strong cohesion between adsorbed C(16)TASal layers.

Biofilm formation and local electrostatic force characteristics of Escherichia coli O157:H7 observed by electrostatic force microscopy

NASA Astrophysics Data System (ADS)

Oh, Y. J.; Jo, W.; Yang, Y.; Park, S.

2007-04-01

The authors report growth media dependence of electrostatic force characteristics in Escherichia coli O157:H7 biofilm through local measurement by electrostatic force microscopy (EFM). The difference values of electrostatic interaction between the bacterial surface and the abiotic surface show an exponential decay behavior during biofilm development. In the EFM data, the biofilm in the low nutrient media shows a faster decay than the biofilm in the rich media. The surface potential in the bacterial cells was changed from 957to149mV. Local characterization of extracellular materials extracted from the bacteria reveals the progress of the biofilm formation and functional complexities.

Computational investigation of non-covalent interactions in 1-butyl 3-methylimidazolium/bis(trifluoromethylsulfonyl)imide [bmim][Tf2N] in EMD and NEMD

NASA Astrophysics Data System (ADS)

Blanco-Díaz, Edgar G.; Vázquez-Montelongo, Erik A.; Cisneros, G. Andrés; Castrejón-González, Edgar Omar

2018-02-01

Non-covalent interactions (NCIs) play a crucial role in the behavior and properties of ionic liquids (ILs). These interactions are particularly important for non-equilibrium properties such as the change in viscosity due to shearing forces (shear viscosity). Therefore, a detailed understanding of these interactions can improve our understanding of these important classes of liquids. Here, we have employed quantum mechanical energy decomposition analysis (EDA) and NCI analysis to investigate a series of representative 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([bmim][Tf2N]) ion pairs extracted from classical equilibrium and non-equilibrium molecular dynamics simulations. EDA based on symmetry-adapted perturbation theory (SAPT) for the complete monomers, as well as fragment SAPT (FSAPT), for the functional fragments has been carried out. In general, the electrostatic component comprises ≈80% of the intermolecular interaction, and significant contributions from other components (induction and dispersion) are also observed, especially for interactions involving bifurcated hydrogen bonds. The FSAPT analysis suggests that caution is warranted when employing simplified assumptions for non-bonded interactions, e.g., focusing only on hydrogen bonds between functional fragments, since this view may not provide a complete picture of the complicated interactions between the ions. In non-equilibrium molecular dynamics, the total interaction energies of some fragments have a significant qualitative change as the shear rate increases. Our results indicate that the inter-fragment interactions play a fundamental role in the viscous behavior of ILs, suggesting that the exclusive use of geometric criteria to analyze inter-molecular interactions in these systems is not sufficient to investigate shear-thinning effects.

Prediction of protein-protein interaction sites using electrostatic desolvation profiles.

PubMed

Fiorucci, Sébastien; Zacharias, Martin

2010-05-19

Protein-protein complex formation involves removal of water from the interface region. Surface regions with a small free energy penalty for water removal or desolvation may correspond to preferred interaction sites. A method to calculate the electrostatic free energy of placing a neutral low-dielectric probe at various protein surface positions has been designed and applied to characterize putative interaction sites. Based on solutions of the finite-difference Poisson equation, this method also includes long-range electrostatic contributions and the protein solvent boundary shape in contrast to accessible-surface-area-based solvation energies. Calculations on a large set of proteins indicate that in many cases (>90%), the known binding site overlaps with one of the six regions of lowest electrostatic desolvation penalty (overlap with the lowest desolvation region for 48% of proteins). Since the onset of electrostatic desolvation occurs even before direct protein-protein contact formation, it may help guide proteins toward the binding region in the final stage of complex formation. It is interesting that the probe desolvation properties associated with residue types were found to depend to some degree on whether the residue was outside of or part of a binding site. The probe desolvation penalty was on average smaller if the residue was part of a binding site compared to other surface locations. Applications to several antigen-antibody complexes demonstrated that the approach might be useful not only to predict protein interaction sites in general but to map potential antigenic epitopes on protein surfaces. Copyright (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Nonlinear Electrostatic Steepening of Whistler Waves: The Guiding Factors and Dynamics in Inhomogeneous Systems

NASA Astrophysics Data System (ADS)

Agapitov, O.; Drake, J. F.; Vasko, I.; Mozer, F. S.; Artemyev, A.; Krasnoselskikh, V.; Angelopoulos, V.; Wygant, J.; Reeves, G. D.

2018-03-01

Whistler mode chorus waves are particularly important in outer radiation belt dynamics due to their key role in controlling the acceleration and scattering of electrons over a very wide energy range. The efficiency of wave-particle resonant interactions is defined by whistler wave properties which have been described by the approximation of plane linear waves propagating through the cold plasma of the inner magnetosphere. However, recent observations of extremely high-amplitude whistlers suggest the importance of nonlinear wave-particle interactions for the dynamics of the outer radiation belt. Oblique chorus waves observed in the inner magnetosphere often exhibit drastically nonsinusoidal (with significant power in the higher harmonics) waveforms of the parallel electric field, presumably due to the feedback from hot resonant electrons. We have considered the nature and properties of such nonlinear whistler waves observed by the Van Allen Probes and Time History of Events and Macroscale Interactions define during Substorms in the inner magnetosphere, and we show that the significant enhancement of the wave electrostatic component can result from whistler wave coupling with the beam-driven electrostatic mode through the resonant interaction with hot electron beams. Being modulated by a whistler wave, the electron beam generates a driven electrostatic mode significantly enhancing the parallel electric field of the initial whistler wave. We confirm this mechanism using a self-consistent particle-in-cell simulation. The nonlinear electrostatic component manifests properties of the beam-driven electron acoustic mode and can be responsible for effective electron acceleration in the inhomogeneous magnetic field.

Proteins feel more than they see: fine-tuning of binding affinity by properties of the non-interacting surface.

PubMed

Kastritis, Panagiotis L; Rodrigues, João P G L M; Folkers, Gert E; Boelens, Rolf; Bonvin, Alexandre M J J

2014-07-15

Protein-protein complexes orchestrate most cellular processes such as transcription, signal transduction and apoptosis. The factors governing their affinity remain elusive however, especially when it comes to describing dissociation rates (koff). Here we demonstrate that, next to direct contributions from the interface, the non-interacting surface (NIS) also plays an important role in binding affinity, especially polar and charged residues. Their percentage on the NIS is conserved over orthologous complexes indicating an evolutionary selection pressure. Their effect on binding affinity can be explained by long-range electrostatic contributions and surface-solvent interactions that are known to determine the local frustration of the protein complex surface. Including these in a simple model significantly improves the affinity prediction of protein complexes from structural models. The impact of mutations outside the interacting surface on binding affinity is supported by experimental alanine scanning mutagenesis data. These results enable the development of more sophisticated and integrated biophysical models of binding affinity and open new directions in experimental control and modulation of biomolecular interactions. Copyright © 2014. Published by Elsevier Ltd.

Calcium and protons affect the interaction of neurotransmitters and anesthetics with anionic lipid membranes.

PubMed

Pérez-Isidoro, Rosendo; Ruiz-Suárez, J C

2016-09-01

We study how zwitterionic and anionic biomembrane models interact with neurotransmitters (NTs) and anesthetics (ATs) in the presence of Ca(2+) and different pH conditions. As NTs we used acetylcholine (ACh), γ-aminobutyric acid (GABA), and l-glutamic acid (LGlu). As ATs, tetracaine (TC), and pentobarbital (PB) were employed. By using differential scanning calorimetry (DSC), we analyzed the changes such molecules produce in the thermal properties of the membranes. We found that calcium and pH play important roles in the interactions of NTs and ATs with the anionic lipid membranes. Changes in pH promote deprotonation of the phosphate groups in anionic phospholipids inducing electrostatic interactions between them and NTs; but if Ca(2+) ions are in the system, these act as bridges. Such interactions impact the physical properties of the membranes in a similar manner that anesthetics do. Beyond the usual biochemical approach, we claim that these effects should be taken into account to understand the excitatory-inhibitory orchestrated balance in the nervous system. Copyright © 2016 Elsevier B.V. All rights reserved.

Electrostatic contribution to the binding stability of protein-protein complexes.

PubMed

Dong, Feng; Zhou, Huan-Xiang

2006-10-01

To investigate roles of electrostatic interactions in protein binding stability, electrostatic calculations were carried out on a set of 64 mutations over six protein-protein complexes. These mutations alter polar interactions across the interface and were selected for putative dominance of electrostatic contributions to the binding stability. Three protocols of implementing the Poisson-Boltzmann model were tested. In vdW4 the dielectric boundary between the protein low dielectric and the solvent high dielectric is defined as the protein van der Waals surface and the protein dielectric constant is set to 4. In SE4 and SE20, the dielectric boundary is defined as the surface of the protein interior inaccessible to a 1.4-A solvent probe, and the protein dielectric constant is set to 4 and 20, respectively. In line with earlier studies on the barnase-barstar complex, the vdW4 results on the large set of mutations showed the closest agreement with experimental data. The agreement between vdW4 and experiment supports the contention of dominant electrostatic contributions for the mutations, but their differences also suggest van der Waals and hydrophobic contributions. The results presented here will serve as a guide for future refinement in electrostatic calculation and inclusion of nonelectrostatic effects. Proteins 2006. (c) 2006 Wiley-Liss, Inc.

Predicting the influence of long-range molecular interactions on macroscopic-scale diffusion by homogenization of the Smoluchowski equation

NASA Astrophysics Data System (ADS)

Kekenes-Huskey, P. M.; Gillette, A. K.; McCammon, J. A.

2014-05-01

The macroscopic diffusion constant for a charged diffuser is in part dependent on (1) the volume excluded by solute "obstacles" and (2) long-range interactions between those obstacles and the diffuser. Increasing excluded volume reduces transport of the diffuser, while long-range interactions can either increase or decrease diffusivity, depending on the nature of the potential. We previously demonstrated [P. M. Kekenes-Huskey et al., Biophys. J. 105, 2130 (2013)] using homogenization theory that the configuration of molecular-scale obstacles can both hinder diffusion and induce diffusional anisotropy for small ions. As the density of molecular obstacles increases, van der Waals (vdW) and electrostatic interactions between obstacle and a diffuser become significant and can strongly influence the latter's diffusivity, which was neglected in our original model. Here, we extend this methodology to include a fixed (time-independent) potential of mean force, through homogenization of the Smoluchowski equation. We consider the diffusion of ions in crowded, hydrophilic environments at physiological ionic strengths and find that electrostatic and vdW interactions can enhance or depress effective diffusion rates for attractive or repulsive forces, respectively. Additionally, we show that the observed diffusion rate may be reduced independent of non-specific electrostatic and vdW interactions by treating obstacles that exhibit specific binding interactions as "buffers" that absorb free diffusers. Finally, we demonstrate that effective diffusion rates are sensitive to distribution of surface charge on a globular protein, Troponin C, suggesting that the use of molecular structures with atomistic-scale resolution can account for electrostatic influences on substrate transport. This approach offers new insight into the influence of molecular-scale, long-range interactions on transport of charged species, particularly for diffusion-influenced signaling events occurring in crowded cellular environments.

A hybrid parallel architecture for electrostatic interactions in the simulation of dissipative particle dynamics

NASA Astrophysics Data System (ADS)

Yang, Sheng-Chun; Lu, Zhong-Yuan; Qian, Hu-Jun; Wang, Yong-Lei; Han, Jie-Ping

2017-11-01

In this work, we upgraded the electrostatic interaction method of CU-ENUF (Yang, et al., 2016) which first applied CUNFFT (nonequispaced Fourier transforms based on CUDA) to the reciprocal-space electrostatic computation and made the computation of electrostatic interaction done thoroughly in GPU. The upgraded edition of CU-ENUF runs concurrently in a hybrid parallel way that enables the computation parallelizing on multiple computer nodes firstly, then further on the installed GPU in each computer. By this parallel strategy, the size of simulation system will be never restricted to the throughput of a single CPU or GPU. The most critical technical problem is how to parallelize a CUNFFT in the parallel strategy, which is conquered effectively by deep-seated research of basic principles and some algorithm skills. Furthermore, the upgraded method is capable of computing electrostatic interactions for both the atomistic molecular dynamics (MD) and the dissipative particle dynamics (DPD). Finally, the benchmarks conducted for validation and performance indicate that the upgraded method is able to not only present a good precision when setting suitable parameters, but also give an efficient way to compute electrostatic interactions for huge simulation systems. Program Files doi:http://dx.doi.org/10.17632/zncf24fhpv.1 Licensing provisions: GNU General Public License 3 (GPL) Programming language: C, C++, and CUDA C Supplementary material: The program is designed for effective electrostatic interactions of large-scale simulation systems, which runs on particular computers equipped with NVIDIA GPUs. It has been tested on (a) single computer node with Intel(R) Core(TM) i7-3770@ 3.40 GHz (CPU) and GTX 980 Ti (GPU), and (b) MPI parallel computer nodes with the same configurations. Nature of problem: For molecular dynamics simulation, the electrostatic interaction is the most time-consuming computation because of its long-range feature and slow convergence in simulation space, which approximately take up most of the total simulation time. Although the parallel method CU-ENUF (Yang et al., 2016) based on GPU has achieved a qualitative leap compared with previous methods in electrostatic interactions computation, the computation capability is limited to the throughput capacity of a single GPU for super-scale simulation system. Therefore, we should look for an effective method to handle the calculation of electrostatic interactions efficiently for a simulation system with super-scale size. Solution method: We constructed a hybrid parallel architecture, in which CPU and GPU are combined to accelerate the electrostatic computation effectively. Firstly, the simulation system is divided into many subtasks via domain-decomposition method. Then MPI (Message Passing Interface) is used to implement the CPU-parallel computation with each computer node corresponding to a particular subtask, and furthermore each subtask in one computer node will be executed in GPU in parallel efficiently. In this hybrid parallel method, the most critical technical problem is how to parallelize a CUNFFT (nonequispaced fast Fourier transform based on CUDA) in the parallel strategy, which is conquered effectively by deep-seated research of basic principles and some algorithm skills. Restrictions: The HP-ENUF is mainly oriented to super-scale system simulations, in which the performance superiority is shown adequately. However, for a small simulation system containing less than 106 particles, the mode of multiple computer nodes has no apparent efficiency advantage or even lower efficiency due to the serious network delay among computer nodes, than the mode of single computer node. References: (1) S.-C. Yang, H.-J. Qian, Z.-Y. Lu, Appl. Comput. Harmon. Anal. 2016, http://dx.doi.org/10.1016/j.acha.2016.04.009. (2) S.-C. Yang, Y.-L. Wang, G.-S. Jiao, H.-J. Qian, Z.-Y. Lu, J. Comput. Chem. 37 (2016) 378. (3) S.-C. Yang, Y.-L. Zhu, H.-J. Qian, Z.-Y. Lu, Appl. Chem. Res. Chin. Univ., 2017, http://dx.doi.org/10.1007/s40242-016-6354-5. (4) Y.-L. Zhu, H. Liu, Z.-W. Li, H.-J. Qian, G. Milano, Z.-Y. Lu, J. Comput. Chem. 34 (2013) 2197.

Urea-mediated protein denaturation: a consensus view.

PubMed

Das, Atanu; Mukhopadhyay, Chaitali

2009-09-24

We have performed all-atom molecular dynamics simulations of three structurally similar small globular proteins in 8 M urea and compared the results with pure aqueous simulations. Protein denaturation is preceded by an initial loss of water from the first solvation shell and consequent in-flow of urea toward the protein. Urea reaches the first solvation shell of the protein mainly due to electrostatic interaction with a considerable contribution coming from the dispersion interaction. Urea shifts the equilibrium from the native to denatured ensemble by making the protein-protein contact less stable than protein-urea contact, which is just the reverse of the condition in pure water, where protein-protein contact is more stable than protein-water contact. We have also seen that water follows urea and reaches the protein interior at later stages of denaturation, while urea preferentially and efficiently solvates different parts of the protein. Solvation of the protein backbone via hydrogen bonding, favorable electrostatic interaction with hydrophilic residues, and dispersion interaction with hydrophobic residues are the key steps through which urea intrudes the core of the protein and denatures it. Why urea is preferred over water for binding to the protein backbone and how urea orients itself toward the protein backbone have been identified comprehensively. All the key components of intermolecular forces are found to play a significant part in urea-induced protein denaturation and also toward the stability of the denatured state ensemble. Changes in water network/structure and dynamical properties and higher degree of solvation of the hydrophobic residues validate the presence of "indirect mechanism" along with the "direct mechanism" and reinforce the effect of urea on protein.

Some improvements in DNA interaction calculations

NASA Technical Reports Server (NTRS)

Egan, J. T.; Swissler, T. J.; Rein, R.

1974-01-01

Calculations are made on specific DNA-type complexes using refined expressions for electrostatic and polarization energies. Dispersion and repulsive terms are included in the evaluation of the total interaction energy. It is shown that the expansion of the electrostatic potential to include multipole moments up to octopole is necessary to achieve convergence of first-order energies. Polarization energies are not as sensitive to this expansion. The calculations also support the usefulness of the hard sphere model for DNA hydrogen bonds and indicate how stacking interactions are influenced by second-order energies.

Packaging signals in single-stranded RNA viruses: nature's alternative to a purely electrostatic assembly mechanism.

PubMed

Stockley, Peter G; Twarock, Reidun; Bakker, Saskia E; Barker, Amy M; Borodavka, Alexander; Dykeman, Eric; Ford, Robert J; Pearson, Arwen R; Phillips, Simon E V; Ranson, Neil A; Tuma, Roman

2013-03-01

The formation of a protective protein container is an essential step in the life-cycle of most viruses. In the case of single-stranded (ss)RNA viruses, this step occurs in parallel with genome packaging in a co-assembly process. Previously, it had been thought that this process can be explained entirely by electrostatics. Inspired by recent single-molecule fluorescence experiments that recapitulate the RNA packaging specificity seen in vivo for two model viruses, we present an alternative theory, which recognizes the important cooperative roles played by RNA-coat protein interactions, at sites we have termed packaging signals. The hypothesis is that multiple copies of packaging signals, repeated according to capsid symmetry, aid formation of the required capsid protein conformers at defined positions, resulting in significantly enhanced assembly efficiency. The precise mechanistic roles of packaging signal interactions may vary between viruses, as we have demonstrated for MS2 and STNV. We quantify the impact of packaging signals on capsid assembly efficiency using a dodecahedral model system, showing that heterogeneous affinity distributions of packaging signals for capsid protein out-compete those of homogeneous affinities. These insights pave the way to a new anti-viral therapy, reducing capsid assembly efficiency by targeting of the vital roles of the packaging signals, and opens up new avenues for the efficient construction of protein nanocontainers in bionanotechnology.

Brownian Dynamics Simulations of Ion Transport through the VDAC

PubMed Central

Lee, Kyu Il; Rui, Huan; Pastor, Richard W.; Im, Wonpil

2011-01-01

It is important to gain a physical understanding of ion transport through the voltage-dependent anion channel (VDAC) because this channel provides primary permeation pathways for metabolites and electrolytes between the cytosol and mitochondria. We performed grand canonical Monte Carlo/Brownian dynamics (GCMC/BD) simulations to explore the ion transport properties of human VDAC isoform 1 (hVDAC1; PDB:2K4T) embedded in an implicit membrane. When the MD-derived, space-dependent diffusion constant was used in the GCMC/BD simulations, the current-voltage characteristics and ion number profiles inside the pore showed excellent agreement with those calculated from all-atom molecular-dynamics (MD) simulations, thereby validating the GCMC/BD approach. Of the 20 NMR models of hVDAC1 currently available, the third one (NMR03) best reproduces both experimental single-channel conductance and ion selectivity (i.e., the reversal potential). In addition, detailed analyses of the ion trajectories, one-dimensional multi-ion potential of mean force, and protein charge distribution reveal that electrostatic interactions play an important role in the channel structure and ion transport relationship. Finally, the GCMC/BD simulations of various mutants based on NMR03 show good agreement with experimental ion selectivity. The difference in ion selectivity between the wild-type and the mutants is the result of altered potential of mean force profiles that are dominated by the electrostatic interactions. PMID:21281575

Quantitative nanoscale electrostatics of viruses

NASA Astrophysics Data System (ADS)

Hernando-Pérez, M.; Cartagena-Rivera, A. X.; Lošdorfer Božič, A.; Carrillo, P. J. P.; San Martín, C.; Mateu, M. G.; Raman, A.; Podgornik, R.; de Pablo, P. J.

2015-10-01

Electrostatics is one of the fundamental driving forces of the interaction between biomolecules in solution. In particular, the recognition events between viruses and host cells are dominated by both specific and non-specific interactions and the electric charge of viral particles determines the electrostatic force component of the latter. Here we probe the charge of individual viruses in liquid milieu by measuring the electrostatic force between a viral particle and the Atomic Force Microscope tip. The force spectroscopy data of co-adsorbed φ29 bacteriophage proheads and mature virions, adenovirus and minute virus of mice capsids is utilized for obtaining the corresponding density of charge for each virus. The systematic differences of the density of charge between the viral particles are consistent with the theoretical predictions obtained from X-ray structural data. Our results show that the density of charge is a distinguishing characteristic of each virus, depending crucially on the nature of the viral capsid and the presence/absence of the genetic material.Electrostatics is one of the fundamental driving forces of the interaction between biomolecules in solution. In particular, the recognition events between viruses and host cells are dominated by both specific and non-specific interactions and the electric charge of viral particles determines the electrostatic force component of the latter. Here we probe the charge of individual viruses in liquid milieu by measuring the electrostatic force between a viral particle and the Atomic Force Microscope tip. The force spectroscopy data of co-adsorbed φ29 bacteriophage proheads and mature virions, adenovirus and minute virus of mice capsids is utilized for obtaining the corresponding density of charge for each virus. The systematic differences of the density of charge between the viral particles are consistent with the theoretical predictions obtained from X-ray structural data. Our results show that the density of charge is a distinguishing characteristic of each virus, depending crucially on the nature of the viral capsid and the presence/absence of the genetic material. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04274g

Electrostatic interactions of colicin E1 with the surface of Escherichia coli total lipid.

PubMed

Tian, Chunhong; Tétreault, Elaine; Huang, Christopher K; Dahms, Tanya E S

2006-06-01

The surface properties of colicin E1, a 522-amino acid protein, and its interaction with monolayers of Escherichia coli (E. coli) total lipid and 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DOPC) were studied using the Langmuir-Blodgett (LB) technique. Colicin E1 is amphiphilic, forming a protein monolayer at the air/buffer interface. The protein is thought to interact with the E. coli total lipid head groups through electrostatic interactions, followed by its insertion into the lipid monolayers. Supported lipid bilayers (SLBs) of E. coli total lipid and DOPC, deposited onto mica at the cell membrane equivalence pressure for E. coli and incubated with colicin E1, were imaged by contact mode atomic force microscopy (CM-AFM). Colicin E1 formed protein aggregates on DOPC SLBs, while E. coli total lipid SLB was deformed following its incubation with colicin E1. Corresponding lateral force images, along with electrostatic surface potentials for colicin E1 P190, imply a direct interaction of colicin E1 with lipid head groups facilitating their charge neutralization.

Charge conservation in electronegativity equalization and its implications for the electrostatic properties of fluctuating-charge models.

PubMed

Chen, Jiahao; Martínez, Todd J

2009-07-28

An analytical solution of fluctuating-charge models using Gaussian elimination allows us to isolate the contribution of charge conservation effects in determining the charge distribution. We use this analytical solution to calculate dipole moments and polarizabilities and show that charge conservation plays a critical role in maintaining the correct translational invariance of the electrostatic properties predicted by these models.

[Molecular dynamics of immune complex of photoadduct-containing DNA with Fab-Anti-DNA antibody fragment].

PubMed

Akberova, N I; Zhmurov, A A; Nevzorova, T A; Litvinov, R I

2016-01-01

Antibodies to DNA play an important role in the pathogenesis of autoimmune diseases. The elucidation of structural mechanisms of both the antigen recognition and the interaction of anti-DNA antibodies with DNA will help to understand the role of DNA-containing immune complexes in various pathologies and can provide a basis for new treatment modalities. Moreover, the DNA-antibody complex is an analog of specific intracellular DNA-protein interactions. In this work, we used in silico molecular dynamic simulations of bimolecular complexes of the dsDNA segment containing the Fab fragment of an anti-DNA antibody to obtain the detailed thermodynamic and structural characteristics of dynamic intermolecular interactions. Using computationally modified crystal structure of the Fab-DNA complex (PDB ID: 3VW3), we studied the equilibrium molecular dynamics of the 64M-5 antibody Fab fragment associated with the dsDNA fragment containing the thymine dimer, the product of DNA photodamage. Amino acid residues that constitute paratopes and the complementary nucleotide epitopes for the Fab-DNA construct were identified. Stacking and electrostatic interactions were found to play the main role in mediating the most specific antibody-dsDNA contacts, while hydrogen bonds were less significant. These findings may shed light on the formation and properties of pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus associated with skin photosensitivity and DNA photodamage.

Intrinsically Disordered Titin PEVK as a Molecular Velcro: Salt-Bridge Dynamics and Elasticity

NASA Astrophysics Data System (ADS)

Forbes, Jeffrey; Tsai, Wanxia; Wittebort, Richard; Wang, Kuan

2009-03-01

Titin is a giant modular protein (3-4 MDa) found in the muscle sarcomere, where the intrinsically disordered and elastic PEVK segment plays a major role in the passive tension of skeletal and heart tissues. We have proposed that salt-bridges play a central role in the elasticity of PEVK. The 50 kDa engineered PEVK polyprotein shows well-resolved NMR spectra at all concentrations. From long-range NOE's, we observed stable K to E salt-bridges. Simulated annealing with NMR restraints yielded a manifold of structures for an exon 172 trimer. Steered molecular dynamics simulations were done to study how the manifold of salt-bridges evolves during the stretching experiment. Repeated SMD simulations at slow velocity (0.0005 nm/ps) showed force spectra consistent with experimental AFM force spectra of the polyprotein. SMD shows that salt-bridges occur even at high degrees of stretch and that these short range interactions are in integral part of the mechanical properties of PEVK. We propose that the long-range, non-stereospecific nature of electrostatic interactions provide a facile mechanism to tether and untether the flexible chains, which in turn affect elasticity as well as control the accessibility of protein-protein interaction to these nanogel-like proteins.

Ab initio study of the electrostatic multipole nature of torsional potentials in CH3SSCH3, CH3SSH, and HOOH

NASA Technical Reports Server (NTRS)

Sokalski, W. A.; Lai, J.; Luo, N.; Sun, S.; Shibata, M.; Ornstein, R.; Rein, R.

1991-01-01

The origin of torsional potentials in H3CSSCH3, H3CSSH, and HOOH and the anisotropy of the local charge distribution has been analyzed in terms of atomic multipoles calculated from the ab initio LCAO-MO-SCF wave function in the 6-31G* basis set. The results indicate that for longer -S-S-bonds the major contribution to these torsional barriers are electrostatic interactions of the atomic multipoles located on two atoms forming the rotated bond. This finding demonstrates the important role of electrostatic 1-2 interatomic interactions, usually neglected in conformational studies. It also opens the possibility to derive directly from accurate ab initio wave functions a simple nonempirical torsional potential involving atomic multipoles of two bonded atoms defining the torsional angle. For shorter -O-O- bonds, use of more precise models and inclusion of 1-3 interactions seems to be necessary.

Local electrostatic interactions determine the diameter of fusion pores

PubMed Central

Guček, Alenka; Jorgačevski, Jernej; Górska, Urszula; Rituper, Boštjan; Kreft, Marko; Zorec, Robert

2015-01-01

In regulated exocytosis vesicular and plasma membranes merge to form a fusion pore in response to stimulation. The nonselective cation HCN channels are involved in the regulation of unitary exocytotic events by at least 2 mechanisms. They can affect SNARE-dependent exocytotic activity indirectly, via the modulation of free intracellular calcium; and/or directly, by altering local cation concentration, which affects fusion pore geometry likely via electrostatic interactions. By monitoring membrane capacitance, we investigated how extracellular cation concentration affects fusion pore diameter in pituitary cells and astrocytes. At low extracellular divalent cation levels predominantly transient fusion events with widely open fusion pores were detected. However, fusion events with predominately narrow fusion pores were present at elevated levels of extracellular trivalent cations. These results show that electrostatic interactions likely help determine the stability of discrete fusion pore states by affecting fusion pore membrane composition. PMID:25835258

AMOEBA 2.0: A physics-first approach to biomolecular simulations

NASA Astrophysics Data System (ADS)

Rackers, Joshua; Ponder, Jay

The goal of the AMOEBA force field project is to use classical physics to understand and predict the nature of interactions between biological molecules. While making significant advances over the past decade, the ultimate goal of predicting binding energies with ``chemical accuracy'' remains elusive. The primary source of this inaccuracy comes from the physics of how molecules interact at short range. For example, despite AMOEBA's advanced treatment of electrostatics, the force field dramatically overpredicts the electrostatic energy of DNA stacking interactions. AMOEBA 2.0 works to correct these errors by including simple, first principles physics-based terms to account for the quantum mechanical nature of these short-range molecular interactions. We have added a charge penetration term that considerably improves the description of electrostatic interactions at short range. We are reformulating the polarization term of AMOEBA in terms of basic physics assertions. And we are reevaluating the van der Waals term to match ab initio energy decompositions. These additions and changes promise to make AMOEBA more predictive. By including more physical detail of the important short-range interactions of biological molecules, we hope to move closer to the ultimate goal of true predictive power.

Cystoviral polymerase complex protein P7 uses its acidic C-terminal tail to regulate the RNA-directed RNA polymerase P2.

PubMed

Alphonse, Sébastien; Arnold, Jamie J; Bhattacharya, Shibani; Wang, Hsin; Kloss, Brian; Cameron, Craig E; Ghose, Ranajeet

2014-07-15

In bacteriophages of the cystovirus family, the polymerase complex (PX) encodes a 75-kDa RNA-directed RNA polymerase (P2) that transcribes the double-stranded RNA genome. Also a constituent of the PX is the essential protein P7 that, in addition to accelerating PX assembly and facilitating genome packaging, plays a regulatory role in transcription. Deletion of P7 from the PX leads to aberrant plus-strand synthesis suggesting its influence on the transcriptase activity of P2. Here, using solution NMR techniques and the P2 and P7 proteins from cystovirus ϕ12, we demonstrate their largely electrostatic interaction in vitro. Chemical shift perturbations on P7 in the presence of P2 suggest that this interaction involves the dynamic C-terminal tail of P7, more specifically an acidic cluster therein. Patterns of chemical shift changes induced on P2 by the P7 C-terminus resemble those seen in the presence of single-stranded RNA suggesting similarities in binding. This association between P2 and P7 reduces the affinity of the former toward template RNA and results in its decreased activity both in de novo RNA synthesis and in extending a short primer. Given the presence of C-terminal acidic tracts on all cystoviral P7 proteins, the electrostatic nature of the P2/P7 interaction is likely conserved within the family and could constitute a mechanism through which P7 regulates transcription in cystoviruses. Copyright © 2014 Elsevier Ltd. All rights reserved.

Binding of cationic pentapeptides with modified side chain lengths to negatively charged lipid membranes: Complex interplay of electrostatic and hydrophobic interactions.

PubMed

Hoernke, Maria; Schwieger, Christian; Kerth, Andreas; Blume, Alfred

2012-07-01

Basic amino acids play a key role in the binding of membrane associated proteins to negatively charged membranes. However, side chains of basic amino acids like lysine do not only provide a positive charge, but also a flexible hydrocarbon spacer that enables hydrophobic interactions. We studied the influence of hydrophobic contributions to the binding by varying the side chain length of pentapeptides with ammonium groups starting with lysine to lysine analogs with shorter side chains, namely omithine (Orn), alpha, gamma-diaminobutyric acid (Dab) and alpha, beta-diaminopropionic acid (Dap). The binding to negatively charged phosphatidylglycerol (PG) membranes was investigated by calorimetry, FT-infrared spectroscopy (FT-IR) and monolayer techniques. The binding was influenced by counteracting and sometimes compensating contributions. The influence of the bound peptides on the lipid phase behavior depends on the length of the peptide side chains. Isothermal titration calorimetry (ITC) experiments showed exothermic and endothermic effects compensating to a different extent as a function of side chain length. The increase in lipid phase transition temperature was more significant for peptides with shorter side chains. FTIR-spectroscopy revealed changes in hydration of the lipid bilayer interface after peptide binding. Using monolayer techniques, the contributions of electrostatic and hydrophobic effects could clearly be observed. Peptides with short side chains induced a pronounced decrease in surface pressure of PG monolayers whereas peptides with additional hydrophobic interactions decreased the surface pressure much less or even lead to an increase, indicating insertion of the hydrophobic part of the side chain into the lipid monolayer.

Theoretical insights into the π-hole interactions in the complexes containing triphosphorus hydride (P3H3) and its derivatives.

PubMed

Wang, Yuehong; Li, Xiaoyan; Zeng, Yanli; Meng, Lingpeng; Zhang, Xueying

2017-04-01

The π-hole of triphosphorus hydride (P 3 H 3 ) and its derivatives Z 3 X 3 (Z = P, As; X = H, F, Cl, Br) was discovered and analyzed. MP2/aug-cc-pVDZ calculations were performed on the π-hole interactions in the HCN...Z 3 X 3 complexes and the mutual influence between π-hole interactions and the hydrogen bond in the HCN...HCN...Z 3 X 3 and HCN...Z 3 X 3 ...HCN complexes studied. The π-hole interaction belongs to the typical closed-shell noncovalent interaction. The linear relationship was found between the most positive electrostatic potential of the π-hole (V S,max ) and the interaction energy. Moreover, the V S,max of the π-hole was also found to be linearly correlated to the electrostatic energy term, indicating the important contribution of the electrostatic energy term to the π-hole interaction. There is positive cooperativity between the π-hole interaction and the hydrogen bond in the termolecular complexes. The π-hole interaction has a greater influence on the hydrogen bond than vice versa. The mutual enhancing effect between the π-hole interaction and the hydrogen bond in the HCN...HCN...Z 3 X 3 complexes is greater than that in the HCN...Z 3 X 3 ...HCN complexes.

Modeling the formation of ordered nano-assemblies comprised by dendrimers and linear polyelectrolytes: The role of Coulombic interactions

NASA Astrophysics Data System (ADS)

Eleftheriou, E.; Karatasos, K.

2012-10-01

Models of mixtures of peripherally charged dendrimers with oppositely charged linear polyelectrolytes in the presence of explicit solvent are studied by means of molecular dynamics simulations. Under the influence of varying strength of electrostatic interactions, these systems appear to form dynamically arrested film-like interconnected structures in the polymer-rich phase. Acting like a pseudo-thermodynamic inverse temperature, the increase of the strength of the Coulombic interactions drive the polymeric constituents of the mixture to a gradual dynamic freezing-in. The timescale of the average density fluctuations of the formed complexes initially increases in the weak electrostatic regime reaching a finite limit as the strength of electrostatic interactions grow. Although the models are overall electrically neutral, during this process the dendrimer/linear complexes develop a polar character with an excess charge mainly close to the periphery of the dendrimers. The morphological characteristics of the resulted pattern are found to depend on the size of the polymer chains on account of the distinct conformational features assumed by the complexed linear polyelectrolytes of different length. In addition, the length of the polymer chain appears to affect the dynamics of the counterions, thus affecting the ionic transport properties of the system. It appears, therefore, that the strength of electrostatic interactions together with the length of the linear polyelectrolytes are parameters to which these systems are particularly responsive, offering thus the possibility for a better control of the resulted structure and the electric properties of these soft-colloidal systems.

Human Atg8-cardiolipin interactions in mitophagy: Specific properties of LC3B, GABARAPL2 and GABARAP.

PubMed

Antón, Zuriñe; Landajuela, Ane; Hervás, Javier H; Montes, L Ruth; Hernández-Tiedra, Sonia; Velasco, Guillermo; Goñi, Felix M; Alonso, Alicia

2016-12-01

The phospholipid cardiolipin (CL) has been proposed to play a role in selective mitochondrial autophagy, or mitophagy. CL externalization to the outer mitochondrial membrane would act as a signal for the human Atg8 ortholog subfamily, MAP1LC3 (LC3). The latter would mediate both mitochondrial recognition and autophagosome formation, ultimately leading to removal of damaged mitochondria. We have applied quantitative biophysical techniques to the study of CL interaction with various Atg8 human orthologs, namely LC3B, GABARAPL2 and GABARAP. We have found that LC3B interacts preferentially with CL over other di-anionic lipids, that CL-LC3B binding occurs with positive cooperativity, and that the CL-LC3B interaction relies only partially on electrostatic forces. CL-induced increased membrane fluidity appears also as an important factor helping LC3B to bind CL. The LC3B C terminus remains exposed to the hydrophilic environment after protein binding to CL-enriched membranes. In intact U87MG human glioblastoma cells rotenone-induced autophagy leads to LC3B translocation to mitochondria and subsequent delivery of mitochondria to lysosomes. We have also observed that GABARAP, but not GABARAPL2, interacts with CL in vitro. However neither GABARAP nor GABARAPL2 were translocated to mitochondria in rotenone-treated U87MG cells. Thus the various human Atg8 orthologs might play specific roles in different autophagic processes.

Bile Acid-Based Drug Delivery Systems for Enhanced Doxorubicin Encapsulation: Comparing Hydrophobic and Ionic Interactions in Drug Loading and Release.

PubMed

Cunningham, Alexander J; Robinson, Mattieu; Banquy, Xavier; Leblond, Jeanne; Zhu, X X

2018-03-05

Doxorubicin (Dox) is a drug of choice in the design of drug delivery systems directed toward breast cancers, but is often limited by loading and control over its release from polymer micelles. Bile acid-based block copolymers present certain advantages over traditional polymer-based systems for drug delivery purposes, since they can enable a higher drug loading via the formation of a reservoir through their aggregation process. In this study, hydrophobic and electrostatic interactions are compared for their influence on Dox loading inside cholic acid based block copolymers. Poly(allyl glycidyl ether) (PAGE) and poly(ethylene glycol) (PEG) were grafted from the cholic acid (CA) core yielding a star-shaped block copolymer with 4 arms (CA-(PAGE- b-PEG) 4 ) and then loaded with Dox via a nanoprecipitation technique. A high Dox loading of 14 wt % was achieved via electrostatic as opposed to hydrophobic interactions with or without oleic acid as a cosurfactant. The electrostatic interactions confer a pH responsiveness to the system. 50% of the loaded Dox was released at pH 5 in comparison to 12% at pH 7.4. The nanoparticles with Dox loaded via hydrophobic interactions did not show such a pH responsiveness. The systems with Dox loaded via electrostatic interactions showed the lowest IC 50 and highest cellular internalization, indicating the pre-eminence of this interaction in Dox loading. The blank formulations are biocompatible and did not show cytotoxicity up to 0.17 mg/mL. The new functionalized star block copolymers based on cholic acid show great potential as drug delivery carriers.

Electrostatic Phenomena on Planetary Surfaces

NASA Astrophysics Data System (ADS)

Calle, Carlos I.

2017-02-01

The diverse planetary environments in the solar system react in somewhat different ways to the encompassing influence of the Sun. These different interactions define the electrostatic phenomena that take place on and near planetary surfaces. The desire to understand the electrostatic environments of planetary surfaces goes beyond scientific inquiry. These environments have enormous implications for both human and robotic exploration of the solar system. This book describes in some detail what is known about the electrostatic environment of the solar system from early and current experiments on Earth as well as what is being learned from the instrumentation on the space exploration missions (NASA, European Space Agency, and the Japanese Space Agency) of the last few decades. It begins with a brief review of the basic principles of electrostatics.

Molecular modeling and multispectroscopic studies of the interaction of mesalamine with bovine serum albumin.

PubMed

Shahabadi, Nahid; Fili, Soraya Moradi

2014-01-24

The interaction of mesalamine (5-aminosalicylic acid (5-ASA)) with bovine serum albumin (BSA) was investigated by fluorescence quenching, absorption spectroscopy, circular dichroism (CD) techniques, and molecular docking. Thermodynamic parameters (ΔH<0 and ΔS 0) indicated that the hydrogen bond and electrostatic forces played the major role in the binding of 5-ASA to BSA. The results of CD and UV-vis spectroscopy showed that the binding of this drug to BSA induces some conformational changes in BSA. Displacement experiments predicted that the binding of 5-ASA to BSA is located within domain III, Sudlows site 2, that these observations were substantiated by molecular docking studies. In addition, the docking result shows that the 5-ASA in its anionic form mainly interacts with Gln-416 residue through one hydrogen bond between H atom of 5-ASA anion and the adjacent O atom of the hydroxyl group of Gln-416. Copyright © 2013 Elsevier B.V. All rights reserved.

Continuum Electrostatics Approaches to Calculating pKas and Ems in Proteins

PubMed Central

Gunner, MR; Baker, Nathan A.

2017-01-01

Proteins change their charge state through protonation and redox reactions as well as through binding charged ligands. The free energy of these reactions are dominated by solvation and electrostatic energies and modulated by protein conformational relaxation in response to the ionization state changes. Although computational methods for calculating these interactions can provide very powerful tools for predicting protein charge states, they include several critical approximations of which users should be aware. This chapter discusses the strengths, weaknesses, and approximations of popular computational methods for predicting charge states and understanding their underlying electrostatic interactions. The goal of this chapter is to inform users about applications and potential caveats of these methods as well as outline directions for future theoretical and computational research. PMID:27497160

Physical and mechanical properties of gelatin-CMC composite films under the influence of electrostatic interactions.

PubMed

Esteghlal, Sara; Niakousari, Mehrdad; Hosseini, Seyed Mohammad Hashem

2018-07-15

The objective of current study was to examine the electrostatic interactions between gelatin and carboxymethyl cellulose (CMC) as a function of pH and mixing ratio (MR) and to observe how the physical and mechanical properties of gelatin-CMC composite films are affected by these interactions. The interaction between biopolymers was studied using turbidometric analysis at different gelatin: CMC MRs and pH values. A reduction in pH and MR enhanced the electrostatic interactions; while, decreased the relative viscosity of mixed system. Physical and mechanical properties of resultant composite films were examined and compared with those of control gelatin films. Changes in the intensity of interactions between the two biopolymers resulted in films with different properties. Polymer complexation led to formation of resistant film networks of less solubility and swellability. Water vapor permeability (WVP) was not significantly (P≤0.05) influenced by incorporating CMC into continuous gelatin films. Composite films prepared at MR of 9:1 and pH opt (corresponding to the maximum amount of interaction) revealed different characteristics such as maximum amounts of WVP and swelling and minimum amounts of tensile strength and solubility. FTIR spectra of composite films confirmed that gelatin and CMC were not covalently bonded. Copyright © 2018 Elsevier B.V. All rights reserved.

Interactions regulating the head-to-tail directed assembly of biological Janus rods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greene, A. C.; Bachand, M.; Gomez, A.

We can generalize the directed, head-to-tail self-assembly of microtubule filaments in the context of Janus colloidal rods. Specifically, their assembly at the tens of micron-length scale involves a careful balance between long-range electrostatic repulsion and short-range attractive forces. We show that the addition of counterion salts increases the rate of directed assembly by screening the electrostatic forces and enhancing the effectiveness of short-range interactions at the microtubule ends.

Interactions regulating the head-to-tail directed assembly of biological Janus rods

DOE PAGES

Greene, A. C.; Bachand, M.; Gomez, A.; ...

2017-03-31

We can generalize the directed, head-to-tail self-assembly of microtubule filaments in the context of Janus colloidal rods. Specifically, their assembly at the tens of micron-length scale involves a careful balance between long-range electrostatic repulsion and short-range attractive forces. We show that the addition of counterion salts increases the rate of directed assembly by screening the electrostatic forces and enhancing the effectiveness of short-range interactions at the microtubule ends.

Coarse-grained electrostatic interactions of coronene: Towards the crystalline phase

NASA Astrophysics Data System (ADS)

Heinemann, Thomas; Palczynski, Karol; Dzubiella, Joachim; Klapp, Sabine H. L.

2015-11-01

In this article, we present and compare two different, coarse-grained approaches to model electrostatic interactions of disc-shaped aromatic molecules, specifically coronene. Our study builds on our previous work [T. Heinemann et al., J. Chem. Phys. 141, 214110 (2014)], where we proposed, based on a systematic coarse-graining procedure starting from the atomistic level, an anisotropic effective (Gay-Berne-like) potential capable of describing van der Waals contributions to the interaction energy. To take into account electrostatics, we introduce, first, a linear quadrupole moment along the symmetry axis of the coronene disc. The second approach takes into account the fact that the partial charges within the molecules are distributed in a ring-like fashion. We then reparametrize the effective Gay-Berne-like potential such that it matches, at short distances, the ring-ring potential. To investigate the validity of these two approaches, we perform many-particle molecular dynamics simulations, focusing on the crystalline phase (karpatite) where electrostatic interaction effects are expected to be particularly relevant for the formation of tilted stacked columns. Specifically, we investigate various structural parameters as well as the melting transition. We find that the second approach yields consistent results with those from experiments despite the fact that the underlying potential decays with the wrong distance dependence at large molecule separations. Our strategy can be transferred to a broader class of molecules, such as benzene or hexabenzocoronene.

Coarse-grained electrostatic interactions of coronene: Towards the crystalline phase.

PubMed

Heinemann, Thomas; Palczynski, Karol; Dzubiella, Joachim; Klapp, Sabine H L

2015-11-07

In this article, we present and compare two different, coarse-grained approaches to model electrostatic interactions of disc-shaped aromatic molecules, specifically coronene. Our study builds on our previous work [T. Heinemann et al., J. Chem. Phys. 141, 214110 (2014)], where we proposed, based on a systematic coarse-graining procedure starting from the atomistic level, an anisotropic effective (Gay-Berne-like) potential capable of describing van der Waals contributions to the interaction energy. To take into account electrostatics, we introduce, first, a linear quadrupole moment along the symmetry axis of the coronene disc. The second approach takes into account the fact that the partial charges within the molecules are distributed in a ring-like fashion. We then reparametrize the effective Gay-Berne-like potential such that it matches, at short distances, the ring-ring potential. To investigate the validity of these two approaches, we perform many-particle molecular dynamics simulations, focusing on the crystalline phase (karpatite) where electrostatic interaction effects are expected to be particularly relevant for the formation of tilted stacked columns. Specifically, we investigate various structural parameters as well as the melting transition. We find that the second approach yields consistent results with those from experiments despite the fact that the underlying potential decays with the wrong distance dependence at large molecule separations. Our strategy can be transferred to a broader class of molecules, such as benzene or hexabenzocoronene.

Electrostatic interaction of positive charges on the surface of Psb31 with photosystem II in the diatom Chaetoceros gracilis.

PubMed

Nagao, Ryo; Suzuki, Takehiro; Okumura, Akinori; Kihira, Tomohiro; Toda, Ayaka; Dohmae, Naoshi; Nakazato, Katsuyoshi; Tomo, Tatsuya

2017-09-01

Psb31, a novel extrinsic protein found in diatom photosystem II (PSII), directly binds to PSII core subunits, independent of the other extrinsic proteins, and functions to maintain optimum oxygen evolution. However, how Psb31 electrostatically interacts with PSII intrinsic proteins remains to be clarified. In this study, we examined electrostatic interaction of Psb31 with PSII complexes isolated from the diatom Chaetoceros gracilis. Positive or negative charges of isolated Psb31 proteins were modified with N-succinimidyl propionate (NSP) or glycine methyl ester (GME), respectively, resulting in formation of uncharged groups. NSP-modified Psb31 did not bind to PSII with a concomitant increase in NSP concentration, whereas GME-modified Psb31 clearly bound to PSII with retention of oxygen-evolving activity, indicating that positive charges of Lys residues and the N-terminus on the surface of Psb31 are involved in electrostatic interactions with PSII intrinsic proteins. Mass spectrometry analysis of NSP-modified Psb31 and sequence comparisons of Psb31 from C. gracilis with other chromophyte algae led to identification of three Lys residues as possible binding sites to PSII. Based on these findings, together with our previous cross-linking study in diatom PSII and a red algal PSII structure, we discuss binding properties of Psb31 with PSII core proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

Charged patchy particle models in explicit salt: Ion distributions, electrostatic potentials, and effective interactions.

PubMed

Yigit, Cemil; Heyda, Jan; Dzubiella, Joachim

2015-08-14

We introduce a set of charged patchy particle models (CPPMs) in order to systematically study the influence of electrostatic charge patchiness and multipolarity on macromolecular interactions by means of implicit-solvent, explicit-ion Langevin dynamics simulations employing the Gromacs software. We consider well-defined zero-, one-, and two-patched spherical globules each of the same net charge and (nanometer) size which are composed of discrete atoms. The studied mono- and multipole moments of the CPPMs are comparable to those of globular proteins with similar size. We first characterize ion distributions and electrostatic potentials around a single CPPM. Although angle-resolved radial distribution functions reveal the expected local accumulation and depletion of counter- and co-ions around the patches, respectively, the orientation-averaged electrostatic potential shows only a small variation among the various CPPMs due to space charge cancellations. Furthermore, we study the orientation-averaged potential of mean force (PMF), the number of accumulated ions on the patches, as well as the CPPM orientations along the center-to-center distance of a pair of CPPMs. We compare the PMFs to the classical Derjaguin-Verwey-Landau-Overbeek theory and previously introduced orientation-averaged Debye-Hückel pair potentials including dipolar interactions. Our simulations confirm the adequacy of the theories in their respective regimes of validity, while low salt concentrations and large multipolar interactions remain a challenge for tractable theoretical descriptions.

Is there a generalized anomeric effect? Analyses from energy components and information-theoretic quantities from density functional reactivity theory

NASA Astrophysics Data System (ADS)

Cao, Xiaofang; Liu, Shaoqian; Rong, Chunying; Lu, Tian; Liu, Shubin

2017-11-01

The nature and origin of the generalized anomeric effect is investigated with energy components and information-theoretic quantities from density functional reactivity theory. Forty-five systems with the general formula of R1-X-CH2-Y-R2 were examined, where R1 and R2 are functional groups and X and Y as electronegative heteroatoms. Our results show that in most cases the effect is valid, and the dominant contribution for the validity of the effect is from the electrostatic interaction. Other contributions such as steric and hyperconjugation play minor but indispensable roles. Its relationship with the conventional anomeric effect is compared and discussed.

Dynamical Generation of Quasi-Stationary Alfvenic Double Layers and Charge Holes and Unified Theory of Quasi-Static and Alfvenic Auroral Arc Formation

NASA Astrophysics Data System (ADS)

Song, Y.; Lysak, R. L.

2015-12-01

Parallel E-fields play a crucial role for the acceleration of charged particles, creating discrete aurorae. However, once the parallel electric fields are produced, they will disappear right away, unless the electric fields can be continuously generated and sustained for a fairly long time. Thus, the crucial question in auroral physics is how to generate such a powerful and self-sustained parallel electric fields which can effectively accelerate charge particles to high energy during a fairly long time. We propose that nonlinear interaction of incident and reflected Alfven wave packets in inhomogeneous auroral acceleration region can produce quasi-stationary non-propagating electromagnetic plasma structures, such as Alfvenic double layers (DLs) and Charge Holes. Such Alfvenic quasi-static structures often constitute powerful high energy particle accelerators. The Alfvenic DL consists of localized self-sustained powerful electrostatic electric fields nested in a low density cavity and surrounded by enhanced magnetic and mechanical stresses. The enhanced magnetic and velocity fields carrying the free energy serve as a local dynamo, which continuously create the electrostatic parallel electric field for a fairly long time. The generated parallel electric fields will deepen the seed low density cavity, which then further quickly boosts the stronger parallel electric fields creating both Alfvenic and quasi-static discrete aurorae. The parallel electrostatic electric field can also cause ion outflow, perpendicular ion acceleration and heating, and may excite Auroral Kilometric Radiation.

Electric-field-induced forces between two surfaces filled with an insulating liquid: the role of adsorbed water

NASA Astrophysics Data System (ADS)

Wang, Yong Jian; Xu, Zuli; Sheng, Ping; Tong, Penger

2014-06-01

A systematic study of the electric-field-induced forces between a solid glass sphere and a flat gold-plated substrate filled with an insulating liquid has been carried out. Using atomic force microscopy, we measure the electrostatic force f(s, V) between the sphere and substrate as a function of the surface separation s and applied voltage V. The measured f(s, V) is found to be well described by an equation for a conducting sphere. Further force measurements for the "wet" porous glass spheres filled with an aqueous solution of urea and the dried porous glass spheres filled with (dry) air suggest that there is a water layer of a few nanometers in thickness adsorbed on the hydrophilic glass surface under ambient conditions. This adsorbed water layer is more conductive than the dielectric core of the glass sphere, making the sphere surface to be at a potential close to that of the cantilever electrode. As a result, the electric field is strongly concentrated in the gap region between the glass sphere and gold-plate substrate and thus their electrostatic attraction is enhanced. This surface conductivity effect is further supported by the thermal gravimetric analysis (TGA) and force response measurements to a time-dependent electric field. The experiment clearly demonstrates that the adsorption of a conductive water layer on a hydrophilic surface plays a dominant role in determining the electrostatic interaction between the dielectric sphere and substrate.

Versatile organic (fullerene)-inorganic (CdTe nanoparticle) nanoensembles.

PubMed

Guldi, Dirk M; Zilbermann, Israel; Anderson, Greg; Kotov, Nicholas A; Tagmatarchis, Nikos; Prato, Maurizio

2004-11-10

Novel organic (positively charged fullerene)-inorganic (negatively charged CdTe nanoparticle) nanoensembles were devised through electrostatic interactions and probed as versatile donor-acceptor hybrids. Photoirradiation of their homogeneous solutions, containing the electrostatically packed components, let to very long-lived (1.3 ms) charge separated states.

Electrostatic 2D assembly of bionanoparticles on a cationic lipid monolayer.

NASA Astrophysics Data System (ADS)

Kewalramani, Sumit; Wang, Suntao; Fukuto, Masafumi; Yang, Lin; Niu, Zhongwei; Nguyen, Giang; Wang, Qian

2010-03-01

We present a grazing-incidence small-angle X-ray scattering (GISAXS) study on 2D assembly of cowpea mosaic virus (CPMV) under a mixed cationic-zwitterionic (DMTAP^+-DMPC) lipid monolayer at the air-water interface. The inter-particle and particle-lipid electrostatic interactions were varied by controlling the subphase pH and the membrane charge density. GISAXS data show that 2D crystals of CPMV are formed above a threshold membrane charge density and only in a narrow pH range just above CPMV's isoelectric point, where the charge on CPMV is expected to be weakly negative. The particle density for the 2D crystals is similar to that for the densest lattice plane in the 3D crystals of CPMV. The results show that the 2D crystallization is achieved in the part of the phase space where the electrostatic interactions are expected to maximize the adsorption of CPMV onto the lipid membrane. This electrostatics-based strategy for controlling interfacial nanoscale assembly should be generally applicable to other nanoparticles.

Quantitative nanoscale electrostatics of viruses.

PubMed

Hernando-Pérez, M; Cartagena-Rivera, A X; Lošdorfer Božič, A; Carrillo, P J P; San Martín, C; Mateu, M G; Raman, A; Podgornik, R; de Pablo, P J

2015-11-07

Electrostatics is one of the fundamental driving forces of the interaction between biomolecules in solution. In particular, the recognition events between viruses and host cells are dominated by both specific and non-specific interactions and the electric charge of viral particles determines the electrostatic force component of the latter. Here we probe the charge of individual viruses in liquid milieu by measuring the electrostatic force between a viral particle and the Atomic Force Microscope tip. The force spectroscopy data of co-adsorbed ϕ29 bacteriophage proheads and mature virions, adenovirus and minute virus of mice capsids is utilized for obtaining the corresponding density of charge for each virus. The systematic differences of the density of charge between the viral particles are consistent with the theoretical predictions obtained from X-ray structural data. Our results show that the density of charge is a distinguishing characteristic of each virus, depending crucially on the nature of the viral capsid and the presence/absence of the genetic material.

Electrostatic Similarities between Protein and Small Molecule Ligands Facilitate the Design of Protein-Protein Interaction Inhibitors

PubMed Central

Zhang, Kam Y. J.

2013-01-01

One of the underlying principles in drug discovery is that a biologically active compound is complimentary in shape and molecular recognition features to its receptor. This principle infers that molecules binding to the same receptor may share some common features. Here, we have investigated whether the electrostatic similarity can be used for the discovery of small molecule protein-protein interaction inhibitors (SMPPIIs). We have developed a method that can be used to evaluate the similarity of electrostatic potentials between small molecules and known protein ligands. This method was implemented in a software called EleKit. Analyses of all available (at the time of research) SMPPII structures indicate that SMPPIIs bear some similarities of electrostatic potential with the ligand proteins of the same receptor. This is especially true for the more polar SMPPIIs. Retrospective analysis of several successful SMPPIIs has shown the applicability of EleKit in the design of new SMPPIIs. PMID:24130741

Electromagnetic and electrostatic emissions at the cusp-magnetosphere interface during substorms

NASA Technical Reports Server (NTRS)

Curtis, S. A.; Fairfield, D. H.; Wu, C. S.

1979-01-01

Strongly peaked electrostatic emissions near 10.0 kHz and electromagnetic emissions near 0.56 kHz have been observed by the VLF wave detector on board Imp 6 on crossings from the earth's magnetosphere into the polar cusp during the occurrence of large magnetospheric substorms. The electrostatic emissions were observed to be closely confined to the cusp-magnetosphere interface. The electromagnetic emissions were of somewhat broader spatial extent and were seen on higher-latitude field lines within the cusp. Using these plasma wave observations and additional information provided by plasma, magnetometer and particle measurements made simultaneously on Imp 6, theories are constructed to explain each of the two classes of emission. The electromagnetic waves are modeled as whistlers, and the electrostatic waves as electron-cyclotron harmonics. The resulting growth rates predict power spectra similar to those observed for both emission classes. The electrostatic waves may play a significant role via enhanced diffusion in the relaxation of the sharp substorm time cusp-magnetosphere boundary to a more diffuse quiet time boundary.

Electrohydrodynamic deformation and interaction of a pair of emulsion drops

NASA Technical Reports Server (NTRS)

Baygents, James C.

1994-01-01

The response of a pair of emulsion drops to the imposition of a uniform electric field is examined. The case studied is that of equal-sized drops whose line of centers is parallel to the axis of the applied field. A new boundary integral solution to the governing equations of the leaky dielectric model is developed; the formulation accounts for the electrostatic and hydrodynamic interactions between the drops, as well as their deformations. Numerical calculations show that, after an initial transient during which the drops primarily deform, the pair drift slowly together due to their electrostatic interactions.

Electrostatic energy and screened charge interaction near the surface of metals with different Fermi surface shape

NASA Astrophysics Data System (ADS)

Gabovich, A. M.; Il'chenko, L. G.; Pashitskii, E. A.; Romanov, Yu. A.

1980-04-01

Using the Poisson equation Green function for a self-consistent field in a spatially inhomogeneous system, expressions for the electrostatic energy and screened charge interaction near the surface of a semi-infinite metal and a thin quantizing film are derived. It is shown that the decrease law and Friedel oscillation amplitude of adsorbed atom indirect interaction are determined by the electron spectrum character and the Fermi surface shape. The results obtained enable us to explain, in particular, the submonolayer adsorbed film structure on the W and Mo surfaces.

Adaptation Mechanism of the Aspartate Receptor: Electrostatics of the Adaptation Subdomain Play a Key Role in Modulating Kinase Activity†

PubMed Central

Starrett, Diane J.; Falke, Joseph J.

2010-01-01

The aspartate receptor of the Escherichia coli and Salmonella typhimurium chemotaxis pathway generates a transmembrane signal that regulates the activity of the cytoplasmic kinase CheA. Previous studies have identified a region of the cytoplasmic domain that is critical to receptor adaptation and kinase regulation. This region, termed the adaptation subdomain, contains a high density of acidic residues, including specific glutamate residues that serve as receptor adaptation sites. However, the mechanism of signal propagation through this region remains poorly understood. This study uses site-directed mutagenesis to neutralize each acidic residue within the subdomain to probe the hypothesis that electrostatics in this region play a significant role in the mechanism of kinase activation and modulation. Each point mutant was tested for its ability to regulate chemotaxis in vivo and kinase activity in vitro. Four point mutants (D273N, E281Q, D288N, and E477Q) were found to superactivate the kinase relative to the wild-type receptor, and all four of these kinase-activating substitutions are located along the same intersubunit interface as the adaptation sites. These activating substitutions retained the wild-type ability of the attractant-occupied receptor to inhibit kinase activity. When combined in a quadruple mutant (D273N/E281Q/D288N/E477Q), the four charge-neutralizing substitutions locked the receptor in a kinase-superactivating state that could not be fully inactivated by the attractant. Similar lock-on character was observed for a charge reversal substitution, D273R. Together, these results implicate the electrostatic interactions at the intersubunit interface as a major player in signal transduction and kinase regulation. The negative charge in this region destabilizes the local structure in a way that enhances conformational dynamics, as detected by disulfide trapping, and this effect is reversed by charge neutralization of the adaptation sites. Finally, two substitutions (E308Q and E463Q) preserved normal kinase activation in vitro but blocked cellular chemotaxis in vivo, suggesting that these sites lie within the docking site of an adaptation enzyme, CheR or CheB. Overall, this study highlights the importance of electrostatics in signal transduction and regulation of kinase activity by the cytoplasmic domain of the aspartate receptor. PMID:15683239

The “Electrostatic-Switch” Mechanism: Monte Carlo Study of MARCKS-Membrane Interaction

PubMed Central

Tzlil, Shelly; Murray, Diana; Ben-Shaul, Avinoam

2008-01-01

The binding of the myristoylated alanine-rich C kinase substrate (MARCKS) to mixed, fluid, phospholipid membranes is modeled with a recently developed Monte Carlo simulation scheme. The central domain of MARCKS is both basic (ζ = +13) and hydrophobic (five Phe residues), and is flanked with two long chains, one ending with the myristoylated N-terminus. This natively unfolded protein is modeled as a flexible chain of “beads” representing the amino acid residues. The membranes contain neutral (ζ = 0), monovalent (ζ = −1), and tetravalent (ζ = −4) lipids, all of which are laterally mobile. MARCKS-membrane interaction is modeled by Debye-Hückel electrostatic potentials and semiempirical hydrophobic energies. In agreement with experiment, we find that membrane binding is mediated by electrostatic attraction of the basic domain to acidic lipids and membrane penetration of its hydrophobic moieties. The binding is opposed by configurational entropy losses and electrostatic membrane repulsion of the two long chains, and by lipid demixing upon adsorption. The simulations provide a physical model for how membrane-adsorbed MARCKS attracts several PIP2 lipids (ζ = −4) to its vicinity, and how phosphorylation of the central domain (ζ = +13 to ζ = +7) triggers an “electrostatic switch”, which weakens both the membrane interaction and PIP2 sequestration. This scheme captures the essence of “discreteness of charge” at membrane surfaces and can examine the formation of membrane-mediated multicomponent macromolecular complexes that function in many cellular processes. PMID:18502797

Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics Study

PubMed Central

2015-01-01

A better understanding of protein aggregation is bound to translate into critical advances in several areas, including the treatment of misfolded protein disorders and the development of self-assembling biomaterials for novel commercial applications. Because of its ubiquity and clinical potential, albumin is one of the best-characterized models in protein aggregation research; but its properties in different conditions are not completely understood. Here, we carried out all-atom molecular dynamics simulations of albumin to understand how electrostatics can affect the conformation of a single albumin molecule just prior to self-assembly. We then analyzed the tertiary structure and solvent accessible surface area of albumin after electrostatically triggered partial denaturation. The data obtained from these single protein simulations allowed us to investigate the effect of electrostatic interactions between two proteins. The results of these simulations suggested that hydrophobic attractions and counterion binding may be strong enough to effectively overcome the electrostatic repulsions between the highly charged monomers. This work contributes to our general understanding of protein aggregation mechanisms, the importance of explicit consideration of free ions in protein solutions, provides critical new insights about the equilibrium conformation of albumin in its partially denatured state at low pH, and may spur significant progress in our efforts to develop biocompatible protein hydrogels driven by electrostatic partial denaturation. PMID:24393011

An anisotropic hydrogel with electrostatic repulsion between cofacially aligned nanosheets

NASA Astrophysics Data System (ADS)

Liu, Mingjie; Ishida, Yasuhiro; Ebina, Yasuo; Sasaki, Takayoshi; Hikima, Takaaki; Takata, Masaki; Aida, Takuzo

2015-01-01

Machine technology frequently puts magnetic or electrostatic repulsive forces to practical use, as in maglev trains, vehicle suspensions or non-contact bearings. In contrast, materials design overwhelmingly focuses on attractive interactions, such as in the many advanced polymer-based composites, where inorganic fillers interact with a polymer matrix to improve mechanical properties. However, articular cartilage strikingly illustrates how electrostatic repulsion can be harnessed to achieve unparalleled functional efficiency: it permits virtually frictionless mechanical motion within joints, even under high compression. Here we describe a composite hydrogel with anisotropic mechanical properties dominated by electrostatic repulsion between negatively charged unilamellar titanate nanosheets embedded within it. Crucial to the behaviour of this hydrogel is the serendipitous discovery of cofacial nanosheet alignment in aqueous colloidal dispersions subjected to a strong magnetic field, which maximizes electrostatic repulsion and thereby induces a quasi-crystalline structural ordering over macroscopic length scales and with uniformly large face-to-face nanosheet separation. We fix this transiently induced structural order by transforming the dispersion into a hydrogel using light-triggered in situ vinyl polymerization. The resultant hydrogel, containing charged inorganic structures that align cofacially in a magnetic flux, deforms easily under shear forces applied parallel to the embedded nanosheets yet resists compressive forces applied orthogonally. We anticipate that the concept of embedding anisotropic repulsive electrostatics within a composite material, inspired by articular cartilage, will open up new possibilities for developing soft materials with unusual functions.

An anisotropic hydrogel with electrostatic repulsion between cofacially aligned nanosheets.

PubMed

Liu, Mingjie; Ishida, Yasuhiro; Ebina, Yasuo; Sasaki, Takayoshi; Hikima, Takaaki; Takata, Masaki; Aida, Takuzo

2015-01-01

Machine technology frequently puts magnetic or electrostatic repulsive forces to practical use, as in maglev trains, vehicle suspensions or non-contact bearings. In contrast, materials design overwhelmingly focuses on attractive interactions, such as in the many advanced polymer-based composites, where inorganic fillers interact with a polymer matrix to improve mechanical properties. However, articular cartilage strikingly illustrates how electrostatic repulsion can be harnessed to achieve unparalleled functional efficiency: it permits virtually frictionless mechanical motion within joints, even under high compression. Here we describe a composite hydrogel with anisotropic mechanical properties dominated by electrostatic repulsion between negatively charged unilamellar titanate nanosheets embedded within it. Crucial to the behaviour of this hydrogel is the serendipitous discovery of cofacial nanosheet alignment in aqueous colloidal dispersions subjected to a strong magnetic field, which maximizes electrostatic repulsion and thereby induces a quasi-crystalline structural ordering over macroscopic length scales and with uniformly large face-to-face nanosheet separation. We fix this transiently induced structural order by transforming the dispersion into a hydrogel using light-triggered in situ vinyl polymerization. The resultant hydrogel, containing charged inorganic structures that align cofacially in a magnetic flux, deforms easily under shear forces applied parallel to the embedded nanosheets yet resists compressive forces applied orthogonally. We anticipate that the concept of embedding anisotropic repulsive electrostatics within a composite material, inspired by articular cartilage, will open up new possibilities for developing soft materials with unusual functions.

Zolpidem, a clinical hypnotic that affects electronic transfer, alters synaptic activity through potential GABA receptors in the nervous system without significant free radical generation.

PubMed

Kovacic, Peter; Somanathan, Ratnasamy

2009-01-01

Zolpidem (trade name Ambien) has attracted much interest as a sleep-inducing agent and also in research. Attention has been centered mainly on receptor binding and electrochemistry in the central nervous system which are briefly addressed herein. A novel integrated approach to mode of action is presented. The pathways to be discussed involve basicity, reduction potential, electrostatics, cell signaling, GABA receptor binding, electron transfer (ET), pharmacodynamics, structure activity relationships (SAR) and side effects. The highly conjugated pyridinium salt formed by protonation of the amidine moiety is proposed to be the active form acting as an ET agent. Extrapolation of reduction potentials for related compounds supports the premise that zolpidem may act as an ET species in vivo. From recent literature reports, electrostatics is believed to play a significant role in drug action. The pyridinium cation displays molecular electrostatic potential which may well play a role energetically or as a bridging mechanism. An SAR analysis points to analogy with other physiologically active xenobiotics, namely benzodiazepines and paraquat in the conjugated iminium category. Inactivity of metabolites indicates that the parent is the active form of zolpidem. Absence of reactive oxygen species and oxidative stress is in line with minor side effects. In contrast, generally, the prior literature contains essentially no discussion of these fundamental biochemical relationships. Pharmacodynamics may play an important role. Concerning behavior at the blood-brain barrier, useful insight can be gained from investigations of the related cationic anesthetics that are structurally related to acetyl choline. Evidently, the neutral form of the drug penetrates the neuronal membrane, with the salt form operating at the receptor. The pathways of zolpidem have several clinical implications since the agent affects sedation, electroencephalographic activity, oxidative metabolites and receptors in the central nervous system. The drug acts at the GABA(A) receptor benzodiazepine site, displaying high and intermediate affinities to various receptor regions. Structural features for tight binding were determined. The sedative and anticonvulsant activities are due to its action on the alpha-1-GABA(A) receptors. One of the common adverse responses to zolpidem is hallucinations. Proposed mechanisms comprise changes in the GABA(A) receptor, pharmacodynamic interactions involving serotonin and neuronal-weak photon emission processes entailing redox phenomena. Reports cite cases of abuse with cravings based on anxiolytic and stimulating actions. It is important to recognize that insight concerning processes at the fundamental, molecular level can translate into beneficial results involving both positive and adverse side effects. In order for this to occur, interdisciplinary interaction is necessary. Suggestions are made for future research aimed at testing the various hypotheses.

Peptide self-assembly: thermodynamics and kinetics.

PubMed

Wang, Juan; Liu, Kai; Xing, Ruirui; Yan, Xuehai

2016-10-21

Self-assembling systems play a significant role in physiological functions and have therefore attracted tremendous attention due to their great potential for applications in energy, biomedicine and nanotechnology. Peptides, consisting of amino acids, are among the most popular building blocks and programmable molecular motifs. Nanostructures and materials assembled using peptides exhibit important potential for green-life new technology and biomedical applications mostly because of their bio-friendliness and reversibility. The formation of these ordered nanostructures pertains to the synergistic effect of various intermolecular non-covalent interactions, including hydrogen-bonding, π-π stacking, electrostatic, hydrophobic, and van der Waals interactions. Therefore, the self-assembly process is mainly driven by thermodynamics; however, kinetics is also a critical factor in structural modulation and function integration. In this review, we focus on the influence of thermodynamic and kinetic factors on structural assembly and regulation based on different types of peptide building blocks, including aromatic dipeptides, amphiphilic peptides, polypeptides, and amyloid-relevant peptides.

Sequence-dependent nucleosome sliding in rotation-coupled and uncoupled modes revealed by molecular simulations

PubMed Central

Tan, Cheng; Takada, Shoji

2017-01-01

While nucleosome positioning on eukaryotic genome play important roles for genetic regulation, molecular mechanisms of nucleosome positioning and sliding along DNA are not well understood. Here we investigated thermally-activated spontaneous nucleosome sliding mechanisms developing and applying a coarse-grained molecular simulation method that incorporates both long-range electrostatic and short-range hydrogen-bond interactions between histone octamer and DNA. The simulations revealed two distinct sliding modes depending on the nucleosomal DNA sequence. A uniform DNA sequence showed frequent sliding with one base pair step in a rotation-coupled manner, akin to screw-like motions. On the contrary, a strong positioning sequence, the so-called 601 sequence, exhibits rare, abrupt transitions of five and ten base pair steps without rotation. Moreover, we evaluated the importance of hydrogen bond interactions on the sliding mode, finding that strong and weak bonds favor respectively the rotation-coupled and -uncoupled sliding movements. PMID:29194442

Explaining reaction mechanisms using the dual descriptor: a complementary tool to the molecular electrostatic potential.

PubMed

Martínez-Araya, Jorge Ignacio

2013-07-01

The intrinsic reactivity of cyanide when interacting with a silver cation was rationalized using the dual descriptor (DD) as a complement to the molecular electrostatic potential (MEP) in order to predict interactions at the local level. It was found that DD accurately explains covalent interactions that cannot be explained by MEP, which focuses on essentially ionic interactions. This allowed the rationalization of the reaction mechanism that yields silver cyanide in the gas phase. Other similar reaction mechanisms involving a silver cation interacting with water, ammonia, and thiosulfate were also explained by the combination of MEP and DD. This analysis provides another example of the usefulness of DD as a tool for gaining a deeper understanding of any reaction mechanism that is mainly governed by covalent interactions.

Electronic charge rearrangement at metal/organic interfaces induced by weak van der Waals interactions

NASA Astrophysics Data System (ADS)

Ferri, Nicola; Ambrosetti, Alberto; Tkatchenko, Alexandre

2017-07-01

Electronic charge rearrangements at interfaces between organic molecules and solid surfaces play a key role in a wide range of applications in catalysis, light-emitting diodes, single-molecule junctions, molecular sensors and switches, and photovoltaics. It is common to utilize electrostatics and Pauli pushback to control the interface electronic properties, while the ubiquitous van der Waals (vdW) interactions are often considered to have a negligible direct contribution (beyond the obvious structural relaxation). Here, we apply a fully self-consistent Tkatchenko-Scheffler vdW density functional to demonstrate that the weak vdW interactions can induce sizable charge rearrangements at hybrid metal/organic systems (HMOS). The complex vdW correlation potential smears out the interfacial electronic density, thereby reducing the charge transfer in HMOS, changes the interface work functions by up to 0.2 eV, and increases the interface dipole moment by up to 0.3 Debye. Our results suggest that vdW interactions should be considered as an additional control parameter in the design of hybrid interfaces with the desired electronic properties.

Hydrogen Bond Networks and Hydrophobic Effects in the Amyloid β30-35 Chain in Water: A Molecular Dynamics Study.

PubMed

Jong, KwangHyok; Grisanti, Luca; Hassanali, Ali

2017-07-24

We have studied the conformational landscape of the C-terminal fragment of the amyloid protein Aβ 30-35 in water using well-tempered metadynamics simulations and found that it resembles an intrinsically disordered protein. The conformational fluctuations of the protein are facilitated by a collective reorganization of both protein and water hydrogen bond networks, combined with electrostatic interactions between termini as well as hydrophobic interactions of the side chains. The stabilization of hydrophobic interactions in one of the conformers involves a collective collapse of the side chains along with a squeeze-out of water sandwiched between them. The charged N- and C-termini play a critical role in stabilizing different types of protein conformations, including those involving contact-ion salt bridges as well as solvent-mediated interactions of the termini and the amide backbone. We have examined this by probing the distribution of directed water wires forming the hydrogen bond network enveloping the polypeptide. Water wires and their fluctuations form an integral part of structural signature of the protein conformation.

Molecular Basis of the Membrane Interaction of the β2e Subunit of Voltage-Gated Ca2+ Channels

PubMed Central

Kim, Dong-Il; Kang, Mooseok; Kim, Sangyeol; Lee, Juhwan; Park, Yongsoo; Chang, Iksoo; Suh, Byung-Chang

2015-01-01

The auxiliary β subunit plays an important role in the regulation of voltage-gated calcium (CaV) channels. Recently, it was revealed that β2e associates with the plasma membrane through an electrostatic interaction between N-terminal basic residues and anionic phospholipids. However, a molecular-level understanding of β-subunit membrane recruitment in structural detail has remained elusive. In this study, using a combination of site-directed mutagenesis, liposome-binding assays, and multiscale molecular-dynamics (MD) simulation, we developed a physical model of how the β2e subunit is recruited electrostatically to the plasma membrane. In a fluorescence resonance energy transfer assay with liposomes, binding of the N-terminal peptide (23 residues) to liposome was significantly increased in the presence of phosphatidylserine (PS) and phosphatidylinositol 4,5-bisphosphate (PIP2). A mutagenesis analysis suggested that two basic residues proximal to Met-1, Lys-2 (K2) and Trp-5 (W5), are more important for membrane binding of the β2e subunit than distal residues from the N-terminus. Our MD simulations revealed that a stretched binding mode of the N-terminus to PS is required for stable membrane attachment through polar and nonpolar interactions. This mode obtained from MD simulations is consistent with experimental results showing that K2A, W5A, and K2A/W5A mutants failed to be targeted to the plasma membrane. We also investigated the effects of a mutated β2e subunit on inactivation kinetics and regulation of CaV channels by PIP2. In experiments with voltage-sensing phosphatase (VSP), a double mutation in the N-terminus of β2e (K2A/W5A) increased the PIP2 sensitivity of CaV2.2 and CaV1.3 channels by ∼3-fold compared with wild-type β2e subunit. Together, our results suggest that membrane targeting of the β2e subunit is initiated from the nonspecific electrostatic insertion of N-terminal K2 and W5 residues into the membrane. The PS-β2e interaction observed here provides a molecular insight into general principles for protein binding to the plasma membrane, as well as the regulatory roles of phospholipids in transporters and ion channels. PMID:26331250

Effects of the dielectric properties of the ceramic-solvent interface on the binding of proteins to oxide ceramics: a non-local electrostatic approach.

PubMed

Rubinstein, Alexander I; Sabirianov, Renat F; Namavar, Fereydoon

2016-10-14

The rapid development of nanoscience and nanotechnology has raised many fundamental questions that significantly impede progress in these fields. In particular, understanding the physicochemical processes at the interface in aqueous solvents requires the development and application of efficient and accurate methods. In the present work we evaluate the electrostatic contribution to the energy of model protein-ceramic complex formation in an aqueous solvent. We apply a non-local (NL) electrostatic approach that accounts for the effects of the short-range structure of the solvent on the electrostatic interactions of the interfacial systems. In this approach the aqueous solvent is considered as a non-ionic liquid, with the rigid and strongly correlated dipoles of the water molecules. We have found that an ordered interfacial aqueous solvent layer at the protein- and ceramic-solvent interfaces reduces the charging energy of both the ceramic and the protein in the solvent, and significantly increases the electrostatic contribution to their association into a complex. This contribution in the presented NL approach was found to be significantly shifted with respect to the classical model at any dielectric constant value of the ceramics. This implies a significant increase of the adsorption energy in the protein-ceramic complex formation for any ceramic material. We show that for several biocompatible ceramics (for example HfO2, ZrO2, and Ta2O5) the above effect predicts electrostatically induced protein-ceramic complex formation. However, in the framework of the classical continuum electrostatic model (the aqueous solvent as a uniform dielectric medium with a high dielectric constant ∼80) the above ceramics cannot be considered as suitable for electrostatically induced complex formation. Our results also show that the protein-ceramic electrostatic interactions can be strong enough to compensate for the unfavorable desolvation effect in the process of protein-ceramic complex formation.

Effects of the dielectric properties of the ceramic-solvent interface on the binding of proteins to oxide ceramics: a non-local electrostatic approach

NASA Astrophysics Data System (ADS)

Rubinstein, Alexander I.; Sabirianov, Renat F.; Namavar, Fereydoon

2016-10-01

The rapid development of nanoscience and nanotechnology has raised many fundamental questions that significantly impede progress in these fields. In particular, understanding the physicochemical processes at the interface in aqueous solvents requires the development and application of efficient and accurate methods. In the present work we evaluate the electrostatic contribution to the energy of model protein-ceramic complex formation in an aqueous solvent. We apply a non-local (NL) electrostatic approach that accounts for the effects of the short-range structure of the solvent on the electrostatic interactions of the interfacial systems. In this approach the aqueous solvent is considered as a non-ionic liquid, with the rigid and strongly correlated dipoles of the water molecules. We have found that an ordered interfacial aqueous solvent layer at the protein- and ceramic-solvent interfaces reduces the charging energy of both the ceramic and the protein in the solvent, and significantly increases the electrostatic contribution to their association into a complex. This contribution in the presented NL approach was found to be significantly shifted with respect to the classical model at any dielectric constant value of the ceramics. This implies a significant increase of the adsorption energy in the protein-ceramic complex formation for any ceramic material. We show that for several biocompatible ceramics (for example HfO2, ZrO2, and Ta2O5) the above effect predicts electrostatically induced protein-ceramic complex formation. However, in the framework of the classical continuum electrostatic model (the aqueous solvent as a uniform dielectric medium with a high dielectric constant ˜80) the above ceramics cannot be considered as suitable for electrostatically induced complex formation. Our results also show that the protein-ceramic electrostatic interactions can be strong enough to compensate for the unfavorable desolvation effect in the process of protein-ceramic complex formation.

DFT study of CO2 and H2O co-adsorption on carbon models of coal surface.

PubMed

Gao, Zhengyang; Ding, Yi

2017-06-01

The moisture content of coal affects the adsorption capacity of CO 2 on the coal surface. Since the hydrogen bonds are formed between H 2 O and oxygen functional group, the H 2 O cluster more easily adsorbs on the coal micropore than CO 2 molecule. The coal micropores are occupied by H 2 O molecules that cannot provide extra space for CO 2 adsorption, which may leads to the reduction of CO 2 adsorption capacity. However, without considering factors of micropore and oxygen functional groups, the co-adsorption mechanisms of CO 2 and adsorbed H 2 O molecule are not clear. Density functional theory (DFT) calculations were performed to elucidate the effect of adsorbed H 2 O to CO 2 adsorption. This study reports some typical coal-H 2 O···CO 2 complexes, along with a detailed analysis of the geometry, energy, electrostatic potential (ESP), atoms in molecules (AIM), reduced density gradient (RDG), and energy decomposition analysis (EDA). The results show that H 2 O molecule can more stably adsorb on the aromatic ring surface than CO 2 molecule, and the absolute values of local ESP maximum and minimum of H 2 O cluster are greater than CO 2 . AIM analysis shows a detailed interaction path and strength between atoms in CO 2 and H 2 O, and RDG analysis shows that the interactions among CO 2 , H 2 O, and coal model belong to weak van der Waals force. EDA indicates that electrostatic and long-range dispersion terms play a primary role in the co-adsorption of CO 2 and H 2 O. According to the DFT calculated results without considering micropore structure and functional group, it is shown that the adsorbed H 2 O can promote CO 2 adsorption on the coal surface. These results demonstrate that the micropore factor plays a dominant role in affecting CO 2 adsorption capacity, the attractive interaction of adsorbed H 2 O to CO 2 makes little contribution.

A "Reverse-Schur" Approach to Optimization With Linear PDE Constraints: Application to Biomolecule Analysis and Design.

PubMed

Bardhan, Jaydeep P; Altman, Michael D; Tidor, B; White, Jacob K

2009-01-01

We present a partial-differential-equation (PDE)-constrained approach for optimizing a molecule's electrostatic interactions with a target molecule. The approach, which we call reverse-Schur co-optimization, can be more than two orders of magnitude faster than the traditional approach to electrostatic optimization. The efficiency of the co-optimization approach may enhance the value of electrostatic optimization for ligand-design efforts-in such projects, it is often desirable to screen many candidate ligands for their viability, and the optimization of electrostatic interactions can improve ligand binding affinity and specificity. The theoretical basis for electrostatic optimization derives from linear-response theory, most commonly continuum models, and simple assumptions about molecular binding processes. Although the theory has been used successfully to study a wide variety of molecular binding events, its implications have not yet been fully explored, in part due to the computational expense associated with the optimization. The co-optimization algorithm achieves improved performance by solving the optimization and electrostatic simulation problems simultaneously, and is applicable to both unconstrained and constrained optimization problems. Reverse-Schur co-optimization resembles other well-known techniques for solving optimization problems with PDE constraints. Model problems as well as realistic examples validate the reverse-Schur method, and demonstrate that our technique and alternative PDE-constrained methods scale very favorably compared to the standard approach. Regularization, which ordinarily requires an explicit representation of the objective function, can be included using an approximate Hessian calculated using the new BIBEE/P (boundary-integral-based electrostatics estimation by preconditioning) method.

A “Reverse-Schur” Approach to Optimization With Linear PDE Constraints: Application to Biomolecule Analysis and Design

PubMed Central

Bardhan, Jaydeep P.; Altman, Michael D.

2009-01-01

We present a partial-differential-equation (PDE)-constrained approach for optimizing a molecule’s electrostatic interactions with a target molecule. The approach, which we call reverse-Schur co-optimization, can be more than two orders of magnitude faster than the traditional approach to electrostatic optimization. The efficiency of the co-optimization approach may enhance the value of electrostatic optimization for ligand-design efforts–in such projects, it is often desirable to screen many candidate ligands for their viability, and the optimization of electrostatic interactions can improve ligand binding affinity and specificity. The theoretical basis for electrostatic optimization derives from linear-response theory, most commonly continuum models, and simple assumptions about molecular binding processes. Although the theory has been used successfully to study a wide variety of molecular binding events, its implications have not yet been fully explored, in part due to the computational expense associated with the optimization. The co-optimization algorithm achieves improved performance by solving the optimization and electrostatic simulation problems simultaneously, and is applicable to both unconstrained and constrained optimization problems. Reverse-Schur co-optimization resembles other well-known techniques for solving optimization problems with PDE constraints. Model problems as well as realistic examples validate the reverse-Schur method, and demonstrate that our technique and alternative PDE-constrained methods scale very favorably compared to the standard approach. Regularization, which ordinarily requires an explicit representation of the objective function, can be included using an approximate Hessian calculated using the new BIBEE/P (boundary-integral-based electrostatics estimation by preconditioning) method. PMID:23055839

irGPU.proton.Net: Irregular strong charge interaction networks of protonatable groups in protein molecules--a GPU solver using the fast multipole method and statistical thermodynamics.

PubMed

Kantardjiev, Alexander A

2015-04-05

A cluster of strongly interacting ionization groups in protein molecules with irregular ionization behavior is suggestive for specific structure-function relationship. However, their computational treatment is unconventional (e.g., lack of convergence in naive self-consistent iterative algorithm). The stringent evaluation requires evaluation of Boltzmann averaged statistical mechanics sums and electrostatic energy estimation for each microstate. irGPU: Irregular strong interactions in proteins--a GPU solver is novel solution to a versatile problem in protein biophysics--atypical protonation behavior of coupled groups. The computational severity of the problem is alleviated by parallelization (via GPU kernels) which is applied for the electrostatic interaction evaluation (including explicit electrostatics via the fast multipole method) as well as statistical mechanics sums (partition function) estimation. Special attention is given to the ease of the service and encapsulation of theoretical details without sacrificing rigor of computational procedures. irGPU is not just a solution-in-principle but a promising practical application with potential to entice community into deeper understanding of principles governing biomolecule mechanisms. © 2015 Wiley Periodicals, Inc.

The bee, the flower, and the electric field: electric ecology and aerial electroreception.

PubMed

Clarke, Dominic; Morley, Erica; Robert, Daniel

2017-09-01

Bees and flowering plants have a long-standing and remarkable co-evolutionary history. Flowers and bees evolved traits that enable pollination, a process that is as important to plants as it is for pollinating insects. From the sensory ecological viewpoint, bee-flower interactions rely on senses such as vision, olfaction, humidity sensing, and touch. Recently, another sensory modality has been unveiled; the detection of the weak electrostatic field that arises between a flower and a bee. Here, we present our latest understanding of how these electric interactions arise and how they contribute to pollination and electroreception. Finite-element modelling and experimental evidence offer new insights into how these interactions are organised and how they can be further studied. Focussing on pollen transfer, we deconstruct some of the salient features of the three ingredients that enable electrostatic interactions, namely the atmospheric electric field, the capacity of bees to accumulate positive charge, and the propensity of plants to be relatively negatively charged. This article also aims at highlighting areas in need of further investigation, where more research is required to better understand the mechanisms of electrostatic interactions and aerial electroreception.

Study of a condition for the mode conversion from purely perpendicular electrostatic waves to electromagnetic waves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalaee, Mohammad Javad, E-mail: mjkalaee@ut.ac.ir; Katoh, Yuto, E-mail: yuto@stpp.gp.tohoku.ac.jp

One of the mechanisms for generating electromagnetic plasma waves (Z-mode and LO-mode) is mode conversion from electrostatic waves into electromagnetic waves in inhomogeneous plasma. Herein, we study a condition required for mode conversion of electrostatic waves propagating purely perpendicular to the ambient magnetic field, by numerically solving the full dispersion relation. An approximate model is derived describing the coupling between electrostatic waves (hot plasma Bernstein mode) and Z-mode waves at the upper hybrid frequency. The model is used to study conditions required for mode conversion from electrostatic waves (electrostatic electron cyclotron harmonic waves, including Bernstein mode) into electromagnetic plasma wavesmore » (LO-mode). It is shown that for mode conversion to occur in inhomogeneous plasma, the angle between the boundary surface and the magnetic field vector should be within a specific range. The range of the angle depends on the norm of the k vector of waves at the site of mode conversion in the inhomogeneous region. The present study reveals that inhomogeneity alone is not a sufficient condition for mode conversion from electrostatic waves to electromagnetic plasma waves and that the angle between the magnetic field and the density gradient plays an important role in the conversion process.« less

Continuum electromechanical modeling of protein-membrane interactions

NASA Astrophysics Data System (ADS)

Zhou, Y. C.; Lu, Benzhuo; Gorfe, Alemayehu A.

2010-10-01

A continuum electromechanical model is proposed to describe the membrane curvature induced by electrostatic interactions in a solvated protein-membrane system. The model couples the macroscopic strain energy of membrane and the electrostatic solvation energy of the system, and equilibrium membrane deformation is obtained by minimizing the electroelastic energy functional with respect to the dielectric interface. The model is illustrated with the systems with increasing geometry complexity and captures the sensitivity of membrane curvature to the permanent and mobile charge distributions.

Dependence of the Linker Histone and Chromatin Condensation on the Nucleosome Environment.

PubMed

Perišić, Ognjen; Schlick, Tamar

2017-08-24

The linker histone (LH), an auxiliary protein that can bind to chromatin and interact with the linker DNA to form stem motifs, is a key element of chromatin compaction. By affecting the chromatin condensation level, it also plays an active role in gene expression. However, the presence and variable concentration of LH in chromatin fibers with different DNA linker lengths indicate that its folding and condensation are highly adaptable and dependent on the immediate nucleosome environment. Recent experimental studies revealed that the behavior of LH in mononucleosomes markedly differs from that in small nucleosome arrays, but the associated mechanism is unknown. Here we report a structural analysis of the behavior of LH in mononucleosomes and oligonucleosomes (2-6 nucleosomes) using mesoscale chromatin simulations. We show that the adapted stem configuration heavily depends on the strength of electrostatic interactions between LH and its parental DNA linkers, and that those interactions tend to be asymmetric in small oligonucleosome systems. Namely, LH in oligonucleosomes dominantly interacts with one DNA linker only, as opposed to mononucleosomes where LH has similar interactions with both linkers and forms a highly stable nucleosome stem. Although we show that the LH condensation depends sensitively on the electrostatic interactions with entering and exiting DNA linkers, other interactions, especially by nonparental cores and nonparental linkers, modulate the structural condensation by softening LH and thus making oligonucleosomes more flexible, in comparison to to mono- and dinucleosomes. We also find that the overall LH/chromatin interactions sensitively depend on the linker length because the linker length determines the maximal nucleosome stem length. For mononucleosomes with DNA linkers shorter than LH, LH condenses fully, while for DNA linkers comparable or longer than LH, the LH extension in mononucleosomes strongly follows the length of DNA linkers, unhampered by neighboring linker histones. Thus, LH is more condensed for mononucleosomes with short linkers, compared to oligonucleosomes, and its orientation is variable and highly environment-dependent. More generally, the work underscores the agility of LH whose folding dynamics critically controls genomic packaging and gene expression.

Uncovering Specific Electrostatic Interactions in the Denatured States of Proteins

PubMed Central

Shen, Jana K.

2010-01-01

The stability and folding of proteins are modulated by energetically significant interactions in the denatured state that is in equilibrium with the native state. These interactions remain largely invisible to current experimental techniques, however, due to the sparse population and conformational heterogeneity of the denatured-state ensemble under folding conditions. Molecular dynamics simulations using physics-based force fields can in principle offer atomistic details of the denatured state. However, practical applications are plagued with the lack of rigorous means to validate microscopic information and deficiencies in force fields and solvent models. This study presents a method based on coupled titration and molecular dynamics sampling of the denatured state starting from the extended sequence under native conditions. The resulting denatured-state pKas allow for the prediction of experimental observables such as pH- and mutation-induced stability changes. I show the capability and use of the method by investigating the electrostatic interactions in the denatured states of wild-type and K12M mutant of NTL9 protein. This study shows that the major errors in electrostatics can be identified by validating the titration properties of the fragment peptides derived from the sequence of the intact protein. Consistent with experimental evidence, our simulations show a significantly depressed pKa for Asp8 in the denatured state of wild-type, which is due to a nonnative interaction between Asp8 and Lys12. Interestingly, the simulation also shows a nonnative interaction between Asp8 and Glu48 in the denatured state of the mutant. I believe the presented method is general and can be applied to extract and validate microscopic electrostatics of the entire folding energy landscape. PMID:20682271

Comparison of all atom, continuum, and linear fitting empirical models for charge screening effect of aqueous medium surrounding a protein molecule

NASA Astrophysics Data System (ADS)

Takahashi, Takuya; Sugiura, Junnnosuke; Nagayama, Kuniaki

2002-05-01

To investigate the role hydration plays in the electrostatic interactions of proteins, the time-averaged electrostatic potential of the B1 domain of protein G in an aqueous solution was calculated with full atomic molecular dynamics simulations that explicitly considers every atom (i.e., an all atom model). This all atom calculated potential was compared with the potential obtained from an electrostatic continuum model calculation. In both cases, the charge-screening effect was fairly well formulated with an effective relative dielectric constant which increased linearly with increasing charge-charge distance. This simulated linear dependence agrees with the experimentally determined linear relation proposed by Pickersgill. Cut-off approximations for Coulomb interactions failed to reproduce this linear relation. Correlation between the all atom model and the continuum models was found to be better than the respective correlation calculated for linear fitting to the two models. This confirms that the continuum model is better at treating the complicated shapes of protein conformations than the simple linear fitting empirical model. We have tried a sigmoid fitting empirical model in addition to the linear one. When weights of all data were treated equally, the sigmoid model, which requires two fitting parameters, fits results of both the all atom and the continuum models less accurately than the linear model which requires only one fitting parameter. When potential values are chosen as weighting factors, the fitting error of the sigmoid model became smaller, and the slope of both linear fitting curves became smaller. This suggests the screening effect of an aqueous medium within a short range, where potential values are relatively large, is smaller than that expected from the linear fitting curve whose slope is almost 4. To investigate the linear increase of the effective relative dielectric constant, the Poisson equation of a low-dielectric sphere in a high-dielectric medium was solved and charges distributed near the molecular surface were indicated as leading to the apparent linearity.

CH/π interactions in metal-porphyrin complexes with pyrrole and chelate rings as hydrogen acceptors.

PubMed

Medaković, Vesna B; Bogdanović, Goran A; Milčić, Miloš K; Janjić, Goran V; Zarić, Snežana D

2012-12-01

CH/π interactions in metal porphyrinato complexes were studied by analyzing data in crystal structures from the Cambridge Structural Database (CSD) and by quantum chemical calculations. The analysis of the data in the CSD shows that both five-membered pyrrole and six-membered chelate rings form CH/π interactions. The interactions occur more frequently with five-membered rings. The analysis of distances in crystal structures and calculated energies show stronger interactions with six-membered chelate rings, indicating that a larger number of interactions with five-membered rings are not the consequence of stronger interactions, but better accessibility of five-membered pyrrole rings. The calculated energies of the interactions with positions in six-membered rings are -2.09 to -2.83 kcal/mol, while the energies with five-membered rings are -2.05 to -2.26 kcal/mol. The results reveal that stronger interactions of six-membered rings are the consequence of stronger electrostatic interactions. Substituents on the porphyrin ring significantly strengthen the interactions. Substituents on the six-membered ring strengthen the interaction energy by about 20%. The results show that CH/π interactions play an important role in molecular recognition of metalloporphyrins. The significant influence of the substituents on interaction energies can be very important for the design of model systems in bioinorganic chemistry. Copyright © 2012 Elsevier Inc. All rights reserved.

Continuum Electrostatics Approaches to Calculating pKas and Ems in Proteins.

PubMed

Gunner, M R; Baker, N A

2016-01-01

Proteins change their charge state through protonation and redox reactions as well as through binding charged ligands. The free energy of these reactions is dominated by solvation and electrostatic energies and modulated by protein conformational relaxation in response to the ionization state changes. Although computational methods for calculating these interactions can provide very powerful tools for predicting protein charge states, they include several critical approximations of which users should be aware. This chapter discusses the strengths, weaknesses, and approximations of popular computational methods for predicting charge states and understanding the underlying electrostatic interactions. The goal of this chapter is to inform users about applications and potential caveats of these methods as well as outline directions for future theoretical and computational research. © 2016 Elsevier Inc. All rights reserved.

Electrostatic antenna space environment interaction study

NASA Technical Reports Server (NTRS)

Katz, I.

1981-01-01

The interactions of the electrostatic antenna with the space environment in both low Earth orbit and geosynchronous orbit are investigated. It is concluded that the electrostatically controlled membrane mirror is a viable concept for space applications. However, great care must be taken to enclose the high voltage electrodes in a Faraday cage structure to separate the high voltage region from the ambient plasma. For this reason, metallized cloth is not acceptable as a membrane material. Conventional spacecraft charging at geosynchronous orbit should not be a problem provided ancillary structures (such as booms) are given nonnegligible conductivity and adequate grounding. Power loss due to plasma electrons entering the high field region is a potentially serious problem. In low earth orbit any opening whatever in the Faraday cage is likely to produce an unacceptable power drain.

Long-range interaction between heterogeneously charged membranes.

PubMed

Jho, Y S; Brewster, R; Safran, S A; Pincus, P A

2011-04-19

Despite their neutrality, surfaces or membranes with equal amounts of positive and negative charge can exhibit long-range electrostatic interactions if the surface charge is heterogeneous; this can happen when the surface charges form finite-size domain structures. These domains can be formed in lipid membranes where the balance of the different ranges of strong but short-ranged hydrophobic interactions and longer-ranged electrostatic repulsion result in a finite, stable domain size. If the domain size is large enough, oppositely charged domains in two opposing surfaces or membranes can be strongly correlated by the electrostatic interactions; these correlations give rise to an attractive interaction of the two membranes or surfaces over separations on the order of the domain size. We use numerical simulations to demonstrate the existence of strong attractions at separations of tens of nanometers. Large line tensions result in larger domains but also increase the charge density within the domain. This promotes correlations and, as a result, increases the intermembrane attraction. On the other hand, increasing the salt concentration increases both the domain size and degree of domain anticorrelation, but the interactions are ultimately reduced due to increased screening. The result is a decrease in the net attraction as salt concentration is increased. © 2011 American Chemical Society

INTERACTIVE COMPUTER MODEL FOR CALCULATING V-I CURVES IN ESPS (ELECTROSTATIC PRECIPITATORS) VERSION 1.0

EPA Science Inventory

The manual describes two microcomputer programs written to estimate the performance of electrostatic precipitators (ESPs): the first, to estimate the electrical conditions for round discharge electrodes in the ESP; and the second, a modification of the EPA/SRI ESP model, to estim...

Structural insight into the role of Streptococcus parasanguinis Fap1 within oral biofilm formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garnett, James A.; Simpson, Peter J.; Taylor, Jonathan

2012-01-06

Highlights: Black-Right-Pointing-Pointer Crystal structure of Streptococcus parasanguinis Fap1-NR{sub {alpha}} at pH 5.0. Black-Right-Pointing-Pointer pH-dependent conformational changes mediated through electrostatic potential of Fap1-NR{sub {alpha}}. Black-Right-Pointing-Pointer Fap1 facilitates pH-dependent biofilms. Black-Right-Pointing-Pointer We model inter-Fap1 biofilm interactions. -- Abstract: The fimbriae-associated protein 1 (Fap1) is a major adhesin of Streptococcus parasanguinis, a primary colonizer of the oral cavity that plays an important role in the formation of dental plaque. Fap1 is an extracellular adhesive surface fibre belonging to the serine-rich repeat protein (SRRP) family, which plays a central role in the pathogenesis of streptococci and staphylococci. The N-terminal adhesive region of Fap1 (Fap1-NR)more » is composed of two domains (Fap1-NR{sub {alpha}} and Fap1-NR{sub {beta}}) and is projected away from the bacterial surface via the extensive serine-rich repeat region, for adhesion to the salivary pellicle. The adhesive properties of Fap1 are modulated through a pH switch in which a reduction in pH results in a rearrangement between the Fap1-NR{sub {alpha}} and Fap1-NR{sub {beta}} domains, which assists in the survival of S. parasanguinis in acidic environments. We have solved the structure of Fap1-NR{sub {alpha}} at pH 5.0 at 3.0 A resolution and reveal how subtle rearrangements of the 3-helix bundle combined with a change in electrostatic potential mediates 'opening' and activation of the adhesive region. Further, we show that pH-dependent changes are critical for biofilm formation and present an atomic model for the inter-Fap1-NR interactions which have been assigned an important role in the biofilm formation.« less

Insights into the Nature of Anesthetic-Protein Interactions: An ONIOM Study.

PubMed

Qiu, Ling; Lin, Jianguo; Bertaccini, Edward J

2015-10-08

Anesthetics have been employed widely to relieve surgical suffering, but their mechanism of action is not yet clear. For over a century, the mechanism of anesthesia was previously thought to be via lipid bilayer interactions. In the present work, a rigorous three-layer ONIOM(M06-2X/6-31+G*:PM6:AMBER) method was utilized to investigate the nature of interactions between several anesthetics and actual protein binding sites. According to the calculated structural features, interaction energies, atomic charges, and electrostatic potential surfaces, the amphiphilic nature of anesthetic-protein interactions was demonstrated for both inhalational and injectable anesthetics. The existence of hydrogen and halogen bonding interactions between anesthetics and proteins was clearly identified, and these interactions served to assist ligand recognition and binding by the protein. Within all complexes of inhalational or injectable anesthetics, the polarization effects play a dominant role over the steric effects and induce a significant asymmetry in the otherwise symmetric atomic charge distributions of the free ligands in vacuo. This study provides new insight into the mechanism of action of general anesthetics in a more rigorous way than previously described. Future rational design of safer anesthetics for an aging and more physiologically vulnerable population will be predicated on this greater understanding of such specific interactions.

Modeling electrostatic and heterogeneity effects on proton dissociation from humic substances

USGS Publications Warehouse

Tipping, E.; Reddy, M.M.; Hurley, M.A.

1990-01-01

The apparent acid dissociation constant of humic substances increases by 2-4 pK units as ionization of the humic carboxylate groups proceeds. This change in apparent acid strength is due in part to the increase in electrical charge on the humic molecules as protons are shed. In addition, proton dissociation reactions are complicated because humic substances are heterogeneous with respect to proton dissociating groups and molecular size. In this paper, we use the Debye-Hu??ckel theory to describe the effects of electrostatic interactions on proton dissociation of humic substances. Simulations show that, for a size-heterogeneous system of molecules, the weight-average molecular weight is preferable to the number-average value for averaging the effects of electrostatic interactions. Analysis of published data on the proton dissociation of fulvic acid from the Suwannee River shows that the electrostatic interactions can be satisfactorily described by a hypothetical homogeneous compound having a molecular weight of 1000 (similar to the experimentally determined weight-average value). Titration data at three ionic strengths, for several fulvic acid concentrations, and in the pH range from 2.9 to 6.4 can be fitted with three adjustable parameters (pK??int values), given information on molecular size and carboxylate group content. ?? 1990 American Chemical Society.

Emission shaping in fluorescent proteins: role of electrostatics and π-stacking.

PubMed

Park, Jae Woo; Rhee, Young Min

2016-02-07

For many decades, simulating the excited state properties of complex systems has been an intriguing but daunting task due to its high computational cost. Here, we apply molecular dynamics based techniques with interpolated potential energy surfaces toward calculating fluorescence spectra of the green fluorescent protein (GFP) and its variants in a statistically meaningful manner. With the GFP, we show that the diverse electrostatic tuning can shape the emission features in many different ways. By computationally modulating the electrostatic interactions between the chromophore phenoxy oxygen and its nearby residues, we demonstrate that we indeed can shift the emission to the blue or to the red side in a predictable manner. We rationalize the shifting effects of individual residues in the GFP based on the responses of both the adiabatic and the diabatic electronic states of the chromophore. We next exhibit that the yellow emitting variant, the Thr203Tyr mutant, generates changes in the electrostatic interactions and an additional π-stacking interaction. These combined effects indeed induce a red shift to emit the fluorescence into the yellow region. With the series of demonstrations, we suggest that our approach can provide sound rationales and useful insights in understanding different responses of various fluorescent complexes, which may be helpful in designing new light emitting proteins and other related systems in future studies.

Surface charge accumulation of particles containing radionuclides in open air

DOE PAGES

Kim, Yong-ha; Yiacoumi, Sotira; Tsouris, Costas

2015-05-01

Radioactivity can induce charge accumulation on radioactive particles. But, electrostatic interactions caused by radioactivity are typically neglected in transport modeling of radioactive plumes because it is assumed that ionizing radiation leads to charge neutralization. The assumption that electrostatic interactions caused by radioactivity are negligible is evaluated here by examining charge accumulation and neutralization on particles containing radionuclides in open air. Moreover, a charge-balance model is employed to predict charge accumulation on radioactive particles. It is shown that particles containing short-lived radionuclides can be charged with multiple elementary charges through radioactive decay. The presence of radioactive particles can significantly modify themore » particle charge distribution in open air and yield an asymmetric bimodal charge distribution, suggesting that strong electrostatic particle interactions may occur during short- and long-range transport of radioactive particles. Possible effects of transported radioactive particles on electrical properties of the local atmosphere are reported. Our study offers insight into transport characteristics of airborne radionuclides. Results are useful in atmospheric transport modeling of radioactive plumes.« less

Effect of cholesterol on electrostatics in lipid-protein films of a pulmonary surfactant.

PubMed

Finot, Eric; Leonenko, Yuri; Moores, Brad; Eng, Lukas; Amrein, Matthias; Leonenko, Zoya

2010-02-02

We report the changes in the electrical properties of the lipid-protein film of pulmonary surfactant produced by excess cholesterol. Pulmonary surfactant (PS) is a complex lipid-protein mixture that forms a molecular film at the interface of the lung's epithelia. The defined molecular arrangement of the lipids and proteins of the surfactant film gives rise to the locally highly variable electrical surface potential of the interface, which becomes considerably altered in the presence of cholesterol. With frequency modulation Kelvin probe force microscopy (FM-KPFM) and force measurements, complemented by theoretical analysis, we showed that excess cholesterol significantly changes the electric field around a PS film because of the presence of nanometer-sized electrostatic domains and affects the electrostatic interaction of an AFM probe with a PS film. These changes in the local electrical field would greatly alter the interaction of the surfactant film with charged species and would immediately impact the manner in which inhaled (often charged) airborne nanoparticles and fibers might interact with the lung interface.

Highly Efficient Computation of the Basal kon using Direct Simulation of Protein-Protein Association with Flexible Molecular Models.

PubMed

Saglam, Ali S; Chong, Lillian T

2016-01-14

An essential baseline for determining the extent to which electrostatic interactions enhance the kinetics of protein-protein association is the "basal" kon, which is the rate constant for association in the absence of electrostatic interactions. However, since such association events are beyond the milliseconds time scale, it has not been practical to compute the basal kon by directly simulating the association with flexible models. Here, we computed the basal kon for barnase and barstar, two of the most rapidly associating proteins, using highly efficient, flexible molecular simulations. These simulations involved (a) pseudoatomic protein models that reproduce the molecular shapes, electrostatic, and diffusion properties of all-atom models, and (b) application of the weighted ensemble path sampling strategy, which enhanced the efficiency of generating association events by >130-fold. We also examined the extent to which the computed basal kon is affected by inclusion of intermolecular hydrodynamic interactions in the simulations.

Sorption of poly(hexamethylenebiguanide) on cellulose: mechanism of binding and molecular recognition.

PubMed

Blackburn, Richard S; Harvey, Anna; Kettle, Lorna L; Payne, John D; Russell, Stephen J

2006-06-20

Antimicrobial agents such as poly(hexamethylene biguanide) (PHMB) find application in medical, apparel, and household textile sectors; although it is understood that certain concentrations need to be applied to achieve suitable performance, there has been very little work published concerning the interactions of the polymer and its adsorption mechanism on cellulose. In this paper, such physical chemistry parameters are examined and related to computational chemistry studies. Adsorption isotherms were constructed: at low concentrations, these were typical Langmuir isotherms; at higher concentrations, they were more indicative of Freundlich isotherms, attributed to a combination of electrostatic and hydrogen-bonding forces, which endorsed computational chemistry proposals. At lower concentrations, electrostatic interactions between PHMB and carboxylic acid groups in the cellulose dominate with a contribution to binding through hydrogen bonding; as the concentration of PHMB increases, hydrogen bonding with cellulose becomes increasingly dominant. At high PHMB concentrations, observations of increasing PHMB adsorption are attributed to monolayer aggregation and multilayer stacking of PHMB through electrostatic interactions with counterions and hydrogen bonding of biguanide groups.

Electrostatic effects on the folding stability of FKBP

NASA Astrophysics Data System (ADS)

Batra, Jyotica; Zhou, Huan-Xiang

2006-11-01

Charged residues play important roles in the folding of proteins and their interactions with biological targets. We have developed computational models for predicting electrostatic contributions to protein folding and binding stability. To rigorously test and further refine these models, we carried out experimental studies on the effects of charge mutations on the folding stability of FKBP. Two close homologues of FKBP, FKBP12 and FKBP12.6, differ in 18 of 107 positions, and 8 of which involve substitutions of charged residues. These 8 substitutions were introduced on FKBP12 and their effects on the folding stability were measured. The changes in unfolding free energy varied from -0.34 to 0.65 kcal/mol. A double and a triple mutation were introduced to accumulate the stabilization effect of individual substitutions, resulting an increase in stability of about 0.84 kcal/mol. On the other hand, neutralizing one or both partners of a conserved salt bridge reduced the stability by as much as 0.64 kcal/mol. These results suggest that charged residues can modulate the folding stability significantly. To further exploit stabilization effects of charged residues, experiments are now underway to introduce charge mutations that are modeled after a thermophilic FKBP.

Three-dimensional structure of the NLRP7 pyrin domain: insight into pyrin-pyrin-mediated effector domain signaling in innate immunity.

PubMed

Pinheiro, Anderson S; Proell, Martina; Eibl, Clarissa; Page, Rebecca; Schwarzenbacher, Robert; Peti, Wolfgang

2010-08-27

The innate immune system provides an initial line of defense against infection. Nucleotide-binding domain- and leucine-rich repeat-containing protein (NLR or (NOD-like)) receptors play a critical role in the innate immune response by surveying the cytoplasm for traces of intracellular invaders and endogenous stress signals. NLRs themselves are multi-domain proteins. Their N-terminal effector domains (typically a pyrin or caspase activation and recruitment domain) are responsible for driving downstream signaling and initiating the formation of inflammasomes, multi-component complexes necessary for cytokine activation. However, the currently available structures of NLR effector domains have not yet revealed the mechanism of their differential modes of interaction. Here, we report the structure and dynamics of the N-terminal pyrin domain of NLRP7 (NLRP7 PYD) obtained by NMR spectroscopy. The NLRP7 PYD adopts a six-alpha-helix bundle death domain fold. A comparison of conformational and dynamics features of the NLRP7 PYD with other PYDs showed distinct differences for helix alpha3 and loop alpha2-alpha3, which, in NLRP7, is stabilized by a strong hydrophobic cluster. Moreover, the NLRP7 and NLRP1 PYDs have different electrostatic surfaces. This is significant, because death domain signaling is driven by electrostatic contacts and stabilized by hydrophobic interactions. Thus, these results provide new insights into NLRP signaling and provide a first molecular understanding of inflammasome formation.

Molecular driving forces defining lipid positions around aquaporin-0

PubMed Central

Aponte-Santamaría, Camilo; Briones, Rodolfo; Schenk, Andreas D.; Walz, Thomas; de Groot, Bert L.

2012-01-01

Lipid–protein interactions play pivotal roles in biological membranes. Electron crystallographic studies of the lens-specific water channel aquaporin-0 (AQP0) revealed atomistic views of such interactions, by providing high-resolution structures of annular lipids surrounding AQP0. It remained unclear, however, whether these lipid structures are representative of the positions of unconstrained lipids surrounding an individual protein, and what molecular determinants define the lipid positions around AQP0. We addressed these questions by using molecular dynamics simulations and crystallographic refinement, and calculated time-averaged densities of dimyristoyl-phosphatidylcholine lipids around AQP0. Our simulations demonstrate that, although the experimentally determined crystallographic lipid positions are constrained by the crystal packing, they appropriately describe the behavior of unconstrained lipids around an individual AQP0 tetramer, and thus likely represent physiologically relevant lipid positions.While the acyl chains were well localized, the lipid head groups were not. Furthermore, in silico mutations showed that electrostatic interactions do not play a major role attracting these phospholipids towards AQP0. Instead, the mobility of the protein crucially modulates the lipid localization and explains the difference in lipid density between extracellular and cytoplasmic leaflets. Moreover, our simulations support a general mechanism in which membrane proteins laterally diffuse accompanied by several layers of localized lipids, with the positions of the annular lipids being influenced the most by the protein surface. We conclude that the acyl chains rather than the head groups define the positions of dimyristoyl-phosphatidylcholine lipids around AQP0. Lipid localization is largely determined by the mobility of the protein surface, whereas hydrogen bonds play an important but secondary role. PMID:22679286

Symmetry-adapted perturbation theory interaction energy decomposition for some noble gas complexes

NASA Astrophysics Data System (ADS)

Cukras, Janusz; Sadlej, Joanna

2008-06-01

This Letter contains a study of the interaction energy in HArF⋯N 2 and HArF⋯P 2 complexes. Symmetry-adapted perturbation theory (SAPT) has been applied to analyze the electrostatic, induction, dispersion and exchange contributions to the total interaction energy. The interaction energy has also been obtained by supermolecular method at the MP2, MP4, CCSD, CCSD(T) levels. The interaction energy for the studied complexes results from a partial cancelation of large attractive electrostatic, induction, dispersion terms by a strong repulsive exchange contribution. The induction and dispersion effects proved to be crucial in establishing the preference for the colinear HArF⋯N 2 and HArF⋯P 2 structures and shift direction of νHAr stretching vibrations.

Heteroaromatic π-Stacking Energy Landscapes

PubMed Central

2014-01-01

In this study we investigate π-stacking interactions of a variety of aromatic heterocycles with benzene using dispersion corrected density functional theory. We calculate extensive potential energy surfaces for parallel-displaced interaction geometries. We find that dispersion contributes significantly to the interaction energy and is complemented by a varying degree of electrostatic interactions. We identify geometric preferences and minimum interaction energies for a set of 13 5- and 6-membered aromatic heterocycles frequently encountered in small drug-like molecules. We demonstrate that the electrostatic properties of these systems are a key determinant for their orientational preferences. The results of this study can be applied in lead optimization for the improvement of stacking interactions, as it provides detailed energy landscapes for a wide range of coplanar heteroaromatic geometries. These energy landscapes can serve as a guide for ring replacement in structure-based drug design. PMID:24773380

Mechanical behavior simulation of MEMS-based cantilever beam using COMSOL multiphysics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Acheli, A., E-mail: aacheli@cdta.dz; Serhane, R.

This paper presents the studies of mechanical behavior of MEMS cantilever beam made of poly-silicon material, using the coupling of three application modes (plane strain, electrostatics and the moving mesh) of COMSOL Multi-physics software. The cantilevers playing a key role in Micro Electro-Mechanical Systems (MEMS) devices (switches, resonators, etc) working under potential shock. This is why they require actuation under predetermined conditions, such as electrostatic force or inertial force. In this paper, we present mechanical behavior of a cantilever actuated by an electrostatic force. In addition to the simplification of calculations, the weight of the cantilever was not taken intomore » account. Different parameters like beam displacement, electrostatics force and stress over the beam have been calculated by finite element method after having defining the geometry, the material of the cantilever model (fixed at one of ends but is free to move otherwise) and his operational space.« less

Statistical field theory description of inhomogeneous polarizable soft matter

NASA Astrophysics Data System (ADS)

Martin, Jonathan M.; Li, Wei; Delaney, Kris T.; Fredrickson, Glenn H.

2016-10-01

We present a new molecularly informed statistical field theory model of inhomogeneous polarizable soft matter. The model is based on fluid elements, referred to as beads, that can carry a net monopole of charge at their center of mass and a fixed or induced dipole through a Drude-type distributed charge approach. The beads are thus polarizable and naturally manifest attractive van der Waals interactions. Beyond electrostatic interactions, beads can be given soft repulsions to sustain fluid phases at arbitrary densities. Beads of different types can be mixed or linked into polymers with arbitrary chain models and sequences of charged and uncharged beads. By such an approach, it is possible to construct models suitable for describing a vast range of soft-matter systems including electrolyte and polyelectrolyte solutions, ionic liquids, polymerized ionic liquids, polymer blends, ionomers, and block copolymers, among others. These bead models can be constructed in virtually any ensemble and converted to complex-valued statistical field theories by Hubbard-Stratonovich transforms. One of the fields entering the resulting theories is a fluctuating electrostatic potential; other fields are necessary to decouple non-electrostatic interactions. We elucidate the structure of these field theories, their consistency with macroscopic electrostatic theory in the absence and presence of external electric fields, and the way in which they embed van der Waals interactions and non-uniform dielectric properties. Their suitability as a framework for computational studies of heterogeneous soft matter systems using field-theoretic simulation techniques is discussed.

Electrostatically Accelerated Coupled Binding and Folding of Intrinsically Disordered Proteins

PubMed Central

Ganguly, Debabani; Otieno, Steve; Waddell, Brett; Iconaru, Luigi; Kriwacki, Richard W.; Chen, Jianhan

2012-01-01

Intrinsically disordered proteins (IDPs) are now recognized to be prevalent in biology, and many potential functional benefits have been discussed. However, the frequent requirement of peptide folding in specific interactions of IDPs could impose a kinetic bottleneck, which could be overcome only by efficient folding upon encounter. Intriguingly, existing kinetic data suggest that specific binding of IDPs is generally no slower than that of globular proteins. Here, we exploited the cell cycle regulator p27Kip1 (p27) as a model system to understand how IDPs might achieve efficient folding upon encounter for facile recognition. Combining experiments and coarse-grained modeling, we demonstrate that long-range electrostatic interactions between enriched charges on p27 and near its binding site on cyclin A not only enhance the encounter rate (i.e., electrostatic steering), but also promote folding-competent topologies in the encounter complexes, allowing rapid subsequent formation of short-range native interactions en route to the specific complex. In contrast, nonspecific hydrophobic interactions, while hardly affecting the encounter rate, can significantly reduce the efficiency of folding upon encounter and lead to slower binding kinetics. Further analysis of charge distributions in a set of known IDP complexes reveals that, although IDP binding sites tend to be more hydrophobic compared to the rest of the target surface, their vicinities are frequently enriched with charges to complement those on IDPs. This observation suggests that electrostatically accelerated encounter and induced folding might represent a prevalent mechanism for promoting facile IDP recognition. PMID:22721951

Statistical field theory description of inhomogeneous polarizable soft matter.

PubMed

Martin, Jonathan M; Li, Wei; Delaney, Kris T; Fredrickson, Glenn H

2016-10-21

We present a new molecularly informed statistical field theory model of inhomogeneous polarizable soft matter. The model is based on fluid elements, referred to as beads, that can carry a net monopole of charge at their center of mass and a fixed or induced dipole through a Drude-type distributed charge approach. The beads are thus polarizable and naturally manifest attractive van der Waals interactions. Beyond electrostatic interactions, beads can be given soft repulsions to sustain fluid phases at arbitrary densities. Beads of different types can be mixed or linked into polymers with arbitrary chain models and sequences of charged and uncharged beads. By such an approach, it is possible to construct models suitable for describing a vast range of soft-matter systems including electrolyte and polyelectrolyte solutions, ionic liquids, polymerized ionic liquids, polymer blends, ionomers, and block copolymers, among others. These bead models can be constructed in virtually any ensemble and converted to complex-valued statistical field theories by Hubbard-Stratonovich transforms. One of the fields entering the resulting theories is a fluctuating electrostatic potential; other fields are necessary to decouple non-electrostatic interactions. We elucidate the structure of these field theories, their consistency with macroscopic electrostatic theory in the absence and presence of external electric fields, and the way in which they embed van der Waals interactions and non-uniform dielectric properties. Their suitability as a framework for computational studies of heterogeneous soft matter systems using field-theoretic simulation techniques is discussed.

Molecular electrostatic potential and "atoms-in-molecules" analyses of the interplay between π-hole and lone pair···π/X-H···π/metal···π interactions.

PubMed

Bauzá, Antonio; Seth, Saikat Kumar; Frontera, Antonio

2018-04-05

Using ab initio calculations, we analyze the interplay between π-hole interactions involving the nitro group of 1,4-dinitrobenzene and lone pair···π (lp···π), C-H···π or metal(M)···π noncovalent interactions. Moreover, we have also used 1,4-phenylenebis(phosphine dioxide) for comparison purposes. Interesting cooperativity effects are found when π-hole (F···N,P) and lp···π/C-H···π/M···π interactions coexist in the same supramolecular assembly. These effects are studied theoretically in terms of energetic and geometric features of the complexes, which are computed by ab initio methods (RI-MP2/def2-TZVP). A charge density analysis using the Bader's theory of "atoms in molecules" is carried out to characterize the interactions and to analyze their strengthening or weakening depending on the variation of charge density at critical points. The importance of electrostatic effects on the mutual influence of the interaction is studied by means of molecular electrostatic potential calculations. By taking advantage of these computational tools, the present study examines interplay of these interactions. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Preferential binding of positive nanoparticles on cell membranes is due to electrostatic interactions: A too simplistic explanation that does not take into account the nanoparticle protein corona.

PubMed

Forest, Valérie; Pourchez, Jérémie

2017-01-01

The internalization of nanoparticles by cells (and more broadly the nanoparticle/cell interaction) is a crucial issue both for biomedical applications (for the design of nanocarriers with enhanced cellular uptake to reach their intracellular therapeutic targets) and in a nanosafety context (as the internalized dose is one of the key factors in cytotoxicity). Many parameters can influence the nanoparticle/cell interaction, among them, the nanoparticle physico-chemical features, and especially the surface charge. It is generally admitted that positive nanoparticles are more uptaken by cells than neutral or negative nanoparticles. It is supposedly due to favorable electrostatic interactions with negatively charged cell membrane. However, this theory seems too simplistic as it does not consider a fundamental element: the nanoparticle protein corona. Indeed, once introduced in a biological medium nanoparticles adsorb proteins at their surface, forming a new interface defining the nanoparticle "biological identity". This adds a new level of complexity in the interactions with biological systems that cannot be any more limited to electrostatic binding. These interactions will then influence cell behavior. Based on a literature review and on an example of our own experience the parameters involved in the nanoparticle protein corona formation as well as in the nanoparticle/cell interactions are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Multipolar electrostatics for proteins: atom-atom electrostatic energies in crambin.

PubMed

Yuan, Yongna; Mills, Matthew J L; Popelier, Paul L A

2014-02-15

Accurate electrostatics necessitates the use of multipole moments centered on nuclei or extra point charges centered away from the nuclei. Here, we follow the former alternative and investigate the convergence behavior of atom-atom electrostatic interactions in the pilot protein crambin. Amino acids are cut out from a Protein Data Bank structure of crambin, as single amino acids, di, or tripeptides, and are then capped with a peptide bond at each side. The atoms in the amino acids are defined through Quantum Chemical Topology (QCT) as finite volume electron density fragments. Atom-atom electrostatic energies are computed by means of a multipole expansion with regular spherical harmonics, up to a total interaction rank of L = ℓA+ ℓB + 1 = 10. The minimum internuclear distance in the convergent region of all the 15 possible types of atom-atom interactions in crambin that were calculated based on single amino acids are close to the values calculated from di and tripeptides. Values obtained at B3LYP/aug-cc-pVTZ and MP2/aug-cc-pVTZ levels are only slightly larger than those calculated at HF/6-31G(d,p) level. This convergence behavior is transferable to the well-known amyloid beta polypeptide Aβ1-42. Moreover, for a selected central atom, the influence of its neighbors on its multipole moments is investigated, and how far away this influence can be ignored is also determined. Finally, the convergence behavior of AMBER becomes closer to that of QCT with increasing internuclear distance. Copyright © 2013 Wiley Periodicals, Inc.

Free-energy calculations reveal the subtle differences in the interactions of DNA bases with α-hemolysin.

PubMed

Manara, Richard M A; Guy, Andrew T; Wallace, E Jayne; Khalid, Syma

2015-02-10

Next generation DNA sequencing methods that utilize protein nanopores have the potential to revolutionize this area of biotechnology. While the technique is underpinned by simple physics, the wild-type protein pores do not have all of the desired properties for efficient and accurate DNA sequencing. Much of the research efforts have focused on protein nanopores, such as α-hemolysin from Staphylococcus aureus. However, the speed of DNA translocation has historically been an issue, hampered in part by incomplete knowledge of the energetics of translocation. Here we have utilized atomistic molecular dynamics simulations of nucleotide fragments in order to calculate the potential of mean force (PMF) through α-hemolysin. Our results reveal specific regions within the pore that play a key role in the interaction with DNA. In particular, charged residues such as D127 and K131 provide stabilizing interactions with the anionic DNA and therefore are likely to reduce the speed of translocation. These regions provide rational targets for pore optimization. Furthermore, we show that the energetic contributions to the protein-DNA interactions are a complex combination of electrostatics and short-range interactions, often mediated by water molecules.

The correlation of adsorption behavior between ciprofloxacin hydrochloride and the active sites of Fe-doped MCM-41

NASA Astrophysics Data System (ADS)

Wu, Ying; Tang, Yiming; Li, Laisheng; Liu, Peihong; Li, Xukai; Chen, Weirui; Xue, Ying

2018-02-01

Fe-MCM-41s with various molar ratios of silicon to iron (20, 40, 80 and 160) were prepared to investigate adsorption properties of ciprofloxacin hydrochloride (CPX) in aqueous solutions. Fe-MCM-41s were characterized by transmission electron microscope (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), nitrogen adsorption/desorption isotherms and infrared spectroscopy (FT-IR). Effects of silicon–iron ratio, adsorbent dosage, pH and temperature were conducted to explore the adsorption mechanism of CPX on Fe-MCM-41. The results showed that the introduction of iron facilitated the absorption quantity for CPX from 20.04 to 83.33 mg g-1 at 120 min of reaction time, which was mainly attributed to surface complexation. The promotion of hydrophobic effect, electrostatic interactions and π-π electron donor–acceptor interaction also played coordinate roles in the adsorption process. The experimental kinetic data followed both the pseudo-second-order and intra-particle diffusion models, while the adsorption isotherm data fit well to Freundlich model at high temperature. Thermodynamic study showed that the adsorption was spontaneous. Under the effect of electrostatic interaction, pH of the solution strongly affected CPX adsorption. Five representative metal cations (Ca, Cu, Ni, Pb and Cd) were chosen to study the effects on CPX adsorption and their complexation. The inhibiting effect of metal cations on CPX adsorption was sequenced in the order of Cu > Ni > Pb > Cd > Ca, which followed the same order as the complexation stability constants between CPX and cations. The Fe-MCM-41 adsorbent possessed excellent reusability for 4 cycles use, suggesting a potential applicability of Fe-MCM-41 to remove CPX in water.

Molecular modeling on porphyrin derivatives as β5 subunit inhibitor of 20S proteasome.

PubMed

Arba, Muhammad; Nur-Hidayat, Andry; Ruslin; Yusuf, Muhammad; Sumarlin; Hertadi, Rukman; Wahyudi, Setyanto Tri; Surantaadmaja, Slamet Ibrahim; Tjahjono, Daryono H

2018-06-01

The ubiquitin-proteasome system plays an important role in protein quality control. Currently, inhibition of the proteasome has been validated as a promising approach in anticancer therapy. The 20S core particle of the proteasome harbors β5 subunit which is a crucial active site in proteolysis. Targeting proteasome β5 subunit which is responsible for the chymotrypsin-like activity of small molecules has been regarded as an important way for achieving therapeutics target. In the present study, a series of porphyrin derivatives bearing either pyridine or pyrazole rings as meso-substituents were designed and evaluated as an inhibitor for the β5 subunit of the proteasome by employing molecular docking and dynamics simulations. The molecular docking was performed with the help of AutoDock 4.2, while molecular dynamics simulation was done using AMBER 14. All compounds bound to the proteasome with similar binding modes, and each porphyrin-proteasome complex was stable during 30 ns MD simulation as indicated by root-mean-square-deviation (RMSD) value. An analysis on protein residue fluctuation of porphyrin binding demonstrates that in all complexes, porphyrin binding produces minor fluctuation on amino acid residues. The molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) free energy calculation shows that the binding affinities of mono-H 2 PyP, bis-H 2 PzP, and tetra-H 2 PyP were comparable with that of the potential inhibitor, HU10. It is noted that the electrostatic interaction increases with the number of meso-substituents, which was favourable for porphyrin binding. The present study shows that both electrostatic and van der Waals interaction are the main force which controls the interaction of porphyrin compounds with the proteasome. Copyright © 2018 Elsevier Ltd. All rights reserved.

Preferential adhesion of surface groups of Bacillus subtilis on gibbsite at different ionic strengths and pHs revealed by ATR-FTIR spectroscopy.

PubMed

Hong, Zhi-Neng; Jiang, Jun; Li, Jiu-Yu; Xu, Ren-Kou

2018-05-01

Adhesion of bacteria onto minerals is a ubiquitous process that plays a central role in many biogeochemical, microbiology and environmental processes in soil and sediment. Although bacterial adhesion onto soil minerals such as phyllosilicates and Fe-oxides have been investigated extensively, little is known about the mechanisms for bacterial attachment onto Al-oxides. Here, we explored the adhesion of Bacillus subtilis onto gibbsite (γ-AlOOH) under various ionic strengths (1, 10, 50, and 100 mM NaCl) and pHs (pH 4, 7, and 9) by in-situ attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. The time evolution of the peak intensities of the attached bacteria suggested that the adhesion underwent an initial rapid reaction followed by a slow pseudo-first-order kinetic stage. Spectral comparison between the attached and free cells, together with the interaction energy calculated with the Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory and the micro-morphology of bacteria-gibbsite complexes, indicated that both electrostatic and chemical (bacterial groups such as phosphate and carboxyl covalently bind to gibbsite) interactions participated in the adhesion processes. Both solution ionic strength (IS) and pH impacted the spectra of attached bacteria, but the peak intensity of different bands changed differently with these two factors, showing a preferential adhesion of surface groups (phosphate, carboxyl, and amide groups) on gibbsite at different conditions. The diverse responses to IS and pH alteration of the forces (chemical bonds, electrostatic attractions, and the hydrophobic interactions) that essentially govern the adhesion might be responsible for the preferential adhesion. These results may help to better understand how bacteria adhere onto soil oxides at molecular scales. Copyright © 2018 Elsevier B.V. All rights reserved.

Electrostatic atomization--Experiment, theory and industrial applications

NASA Astrophysics Data System (ADS)

Okuda, H.; Kelly, Arnold J.

1996-05-01

Experimental and theoretical research has been initiated at the Princeton Plasma Physics Laboratory on the electrostatic atomization process in collaboration with Charged Injection Corporation. The goal of this collaboration is to set up a comprehensive research and development program on the electrostatic atomization at the Princeton Plasma Physics Laboratory so that both institutions can benefit from the collaboration. Experimental, theoretical and numerical simulation approaches are used for this purpose. An experiment consisting of a capillary sprayer combined with a quadrupole mass filter and a charge detector was installed at the Electrostatic Atomization Laboratory to study fundamental properties of the charged droplets such as the distribution of charges with respect to the droplet radius. In addition, a numerical simulation model is used to study interaction of beam electrons with atmospheric pressure water vapor, supporting an effort to develop an electrostatic water mist fire-fighting nozzle.

Reactivity of etoricoxib based on computational study of molecular orbitals, molecular electrostatic potential surface and Mulliken charge analysis

NASA Astrophysics Data System (ADS)

Sachdeva, Ritika; Soni, Abhinav; Singh, V. P.; Saini, G. S. S.

2018-05-01

Etoricoxib is one of the selective cyclooxygenase inhibitor drug which plays a significant role in the pharmacological management of arthritis and pain. The theoretical investigation of its reactivity is done using Density Functional Theory calculations. Molecular Electrostatic Potential Surface of etoricoxib and its Mulliken atomic charge distribution are used for the prediction of its electrophilic and nucleophilic sites. The detailed analysis of its frontier molecular orbitals is also done.

Electrostatic attraction between neutral microdroplets by ion fluctuations

NASA Astrophysics Data System (ADS)

Sheng, Yu-Jane; Tsao, Heng-Kwong

2004-06-01

The interaction between two aqueous droplets containing ions is investigated. The ion-fluctuation correlation gives rise to attraction between two neutral microdroplets, similar to the van der Waals interaction between neutral atoms. Electrostatic attraction consists of contributions from various induced multipole-multipole interactions, including dipole-dipole < P2z >2 r-6 , dipole-quadrupole < P2z > < Q 2zz > r-8 , dipole-octupole < P2z > < O 2zzz > r-10 , and quadrupole-quadrupole interactions < Q 2zz >2 r-10 . The mean-square multipole moments are determined analytically by linear response theory. The fluctuation-driven attraction is so strong at short distance that it may dominate over the Coulomb repulsion between like-charged droplets. These theoretical results are confirmed by Monte Carlo simulations.

Electrostatic attraction between neutral microdroplets by ion fluctuations.

PubMed

Sheng, Yu-Jane; Tsao, Heng-Kwong

2004-06-01

The interaction between two aqueous droplets containing ions is investigated. The ion-fluctuation correlation gives rise to attraction between two neutral microdroplets, similar to the van der Waals interaction between neutral atoms. Electrostatic attraction consists of contributions from various induced multipole-multipole interactions, including dipole-dipole < P(2)(z) >(2) r(-6), dipole-quadrupole < P(2)(z) > < Q (2)(zz ) > r(-8), dipole-octupole < P(2)(z) > < O (2)(zzz ) > r(-10), and quadrupole-quadrupole interactions < Q (2)(zz ) >(2) r(-10). The mean-square multipole moments are determined analytically by linear response theory. The fluctuation-driven attraction is so strong at short distance that it may dominate over the Coulomb repulsion between like-charged droplets. These theoretical results are confirmed by Monte Carlo simulations.

Modeling salt-mediated electrostatics of macromolecules: the discrete surface charge optimization algorithm and its application to the nucleosome.

PubMed

Beard, D A; Schlick, T

2001-01-01

Much progress has been achieved on quantitative assessment of electrostatic interactions on the all-atom level by molecular mechanics and dynamics, as well as on the macroscopic level by models of continuum solvation. Bridging of the two representations-an area of active research-is necessary for studying integrated functions of large systems of biological importance. Following perspectives of both discrete (N-body) interaction and continuum solvation, we present a new algorithm, DiSCO (Discrete Surface Charge Optimization), for economically describing the electrostatic field predicted by Poisson-Boltzmann theory using a discrete set of Debye-Hückel charges distributed on a virtual surface enclosing the macromolecule. The procedure in DiSCO relies on the linear behavior of the Poisson-Boltzmann equation in the far zone; thus contributions from a number of molecules may be superimposed, and the electrostatic potential, or equivalently the electrostatic field, may be quickly and efficiently approximated by the summation of contributions from the set of charges. The desired accuracy of this approximation is achieved by minimizing the difference between the Poisson-Boltzmann electrostatic field and that produced by the linearized Debye-Hückel approximation using our truncated Newton optimization package. DiSCO is applied here to describe the salt-dependent electrostatic environment of the nucleosome core particle in terms of several hundred surface charges. This representation forms the basis for modeling-by dynamic simulations (or Monte Carlo)-the folding of chromatin. DiSCO can be applied more generally to many macromolecular systems whose size and complexity warrant a model resolution between the all-atom and macroscopic levels. Copyright 2000 John Wiley & Sons, Inc.

Probing the interplay between amyloidogenic proteins and membranes using lipid monolayers and bilayers.

PubMed

Relini, Annalisa; Marano, Nadia; Gliozzi, Alessandra

2014-05-01

Many degenerative diseases such as Alzheimer's and Parkinson's involve proteins that have a tendency to misfold and aggregate eventually forming amyloid fibers. This review describes the use of monolayers, bilayers, supported membranes, and vesicles as model systems that have helped elucidate the mechanisms and consequences of the interactions between amyloidogenic proteins and membranes. These are twofold: membranes favor the formation of amyloid structures and these induce damage in those membranes. We describe studies that show how interfaces, especially charged ones, favor amyloidogenic protein aggregation by several means. First, surfaces increase the effective protein concentration reducing a three-dimensional system to a two-dimensional one. Second, charged surfaces allow electrostatic interactions with the protein. Anionic lipids as well as rafts, rich in cholesterol and gangliosides, prove to play an especially important role. Finally, these amphipathic systems also offer a hydrophobic environment favoring conformational changes, oligomerization, and eventual formation of mature fibers. In addition, we examine several models for membrane permeabilization: protein pores, leakage induced by extraction of lipids, chaotic pores, and membrane tension, presenting illustrative examples of experimental evidence in support of these models. The picture that emerges from recent work is one where more than one mechanism is in play. Which mechanism prevails depends on the protein, its aggregation state, and the lipid environment in which the interactions occur. © 2013.

Implications of hydrogen/halogen-bond in the stabilization of confined water and anion-water clusters by a cationic receptor

NASA Astrophysics Data System (ADS)

Hoque, Md. Najbul; Das, Gopal

2016-03-01

Anion complexation of benzene capped flexible tripodal receptor and solid state stabilization of discrete hybrid anion-water or infinite water clusters by various supramolecular interactions are reported here. The crystal structure of the receptor in protonated states shows all the three arms projected in one direction. We structurally demonstrate discrete fluoride-water cluster [F2-H2O]2- and square shaped chloride-water cluster [Cl2-(H2O)2]2- inside the cationic channel of the receptor. Structural analysis also reveals that these clusters are stabilized inside the channel through active participation of N/C/Ow‧H⋯Ow, N/C/Ow‧H⋯X- (X- = F-, Cl- and I-) H-bonds and electrostatic interactions. Moreover, C-H⋯π and π⋯π types weak intermolecular interactions appear to play crucial role in supramolecular assembly of receptor. Additionally, on treatment with hydroiodic acid (HI) L resulted zwitterionic iodide complex. Crystal structure reveals the presence of S···I halogen bonded dimer, I2···I halogen bond, 1D infinite water chain and neutral iodine molecules. It is comprehensible that ligand basal structure (benzene capped and N-bridge head in two tripodal) play crucial roles in the formation of diverse halide-water cluster. All structures were well examined by different techniques such as NMR, IR, TGA, DSC, PXRD and XRD.

Hierarchy of the Collective Effects in Water Clusters.

PubMed

Bakó, Imre; Mayer, István

2016-02-04

The results of dipole moment as well as of intra- and intermolecular bond order calculations indicate the big importance of collective electrostatic effects caused by the nonimmediate environment in liquid water models. It is also discussed how these collective effects are built up as consequences of the electrostatic and quantum chemical interactions in water clusters.

Charge regulation at semiconductor-electrolyte interfaces.

PubMed

Fleharty, Mark E; van Swol, Frank; Petsev, Dimiter N

2015-07-01

The interface between a semiconductor material and an electrolyte solution has interesting and complex electrostatic properties. Its behavior will depend on the density of mobile charge carriers that are present in both phases as well as on the surface chemistry at the interface through local charge regulation. The latter is driven by chemical equilibria involving the immobile surface groups and the potential determining ions in the electrolyte solution. All these lead to an electrostatic potential distribution that propagate such that the electrolyte and the semiconductor are dependent on each other. Hence, any variation in the charge density in one phase will lead to a response in the other. This has significant implications on the physical properties of single semiconductor-electrolyte interfaces and on the electrostatic interactions between semiconductor particles suspended in electrolyte solutions. The present paper expands on our previous publication (Fleharty et al., 2014) and offers new results on the electrostatics of single semiconductor interfaces as well as on the interaction of charged semiconductor colloids suspended in electrolyte solution. Copyright © 2014 Elsevier Inc. All rights reserved.

An anti-DNA antibody prefers damaged dsDNA over native.

PubMed

Akberova, N I; Zhmurov, A A; Nevzorova, T A; Litvinov, R I

2017-01-01

DNA-protein interactions, including DNA-antibody complexes, have both fundamental and practical significance. In particular, antibodies against double-stranded DNA play an important role in the pathogenesis of autoimmune diseases. Elucidation of structural mechanisms of an antigen recognition and interaction of anti-DNA antibodies provides a basis for understanding the role of DNA-containing immune complexes in human pathologies and for new treatments. Here we used Molecular Dynamic simulations of bimolecular complexes of a segment of dsDNA with a monoclonal anti-DNA antibody's Fab-fragment to obtain detailed structural and physical characteristics of the dynamic intermolecular interactions. Using a computationally modified crystal structure of a Fab-DNA complex (PDB: 3VW3), we studied in silico equilibrium Molecular Dynamics of the Fab-fragment associated with two homologous dsDNA fragments, containing or not containing dimerized thymine, a product of DNA photodamage. The Fab-fragment interactions with the thymine dimer-containing DNA was thermodynamically more stable than with the native DNA. The amino acid residues constituting a paratope and the complementary nucleotide epitopes for both Fab-DNA constructs were identified. Stacking and electrostatic interactions were shown to play the main role in the antibody-dsDNA contacts, while hydrogen bonds were less significant. The aggregate of data show that the chemically modified dsDNA (containing a covalent thymine dimer) has a higher affinity toward the antibody and forms a stronger immune complex. These findings provide a mechanistic insight into formation and properties of the pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus, associated with skin photosensibilization and DNA photodamage.

Mapping the Interaction Anatomy of BmP02 on Kv1.3 Channel

NASA Astrophysics Data System (ADS)

Wu, B.; Wu, B. F.; Feng, Y. J.; Tao, J.; Ji, Y. H.

2016-07-01

The potassium channel Kv 1.3 plays a vital part in the activation of T lymphocytes and is an attractive pharmacological target for autoimmune diseases. BmP02, a 28-residue peptide isolated from Chinese scorpion (Buthus martensi Karsch) venom, is a potent and selective Kv1.3 channel blocker. However, the mechanism through which BmP02 recognizes and inhibits the Kv1.3 channel is still unclear. In the present study, a complex molecular model of Kv1.3-BmP02 was developed by docking analysis and molecular dynamics simulations. From these simulations, it appears the large β-turn (residues 10-16) of BmP02 might be the binding interface with Kv 1.3. These results were confirmed by scanning alanine mutagenesis of BmP02, which identified His9, Lys11 and Lys13, which lie within BmP02’s β-turn, as key residues for interacting with Kv1.3. Based on these results and molecular modeling, two negatively charged residues of Kv1.3, D421 and D422, located in turret region, were predicted to act as the binding site for BmP02. Mutation of these residues reduced sensitivity of Kv 1.3 to BmP02 inhibition, suggesting that electrostatic interactions play a crucial role in Kv1.3-BmP02 interaction. This study revealed the molecular basis of Kv 1.3 recognition by BmP02 venom, and provides a novel interaction model for Kv channel-specific blocker complex, which may help guide future drug-design for Kv1.3-related channelopathies.

Light-scattering studies of protein solutions: role of hydration in weak protein-protein interactions.

PubMed

Paliwal, A; Asthagiri, D; Abras, D; Lenhoff, A M; Paulaitis, M E

2005-09-01

We model the hydration contribution to short-range electrostatic/dispersion protein interactions embodied in the osmotic second virial coefficient, B(2), by adopting a quasi-chemical description in which water molecules associated with the protein are identified through explicit molecular dynamics simulations. These water molecules reduce the surface complementarity of highly favorable short-range interactions, and therefore can play an important role in mediating protein-protein interactions. Here we examine this quasi-chemical view of hydration by predicting the interaction part of B(2) and comparing our results with those derived from light-scattering measurements of B(2) for staphylococcal nuclease, lysozyme, and chymotrypsinogen at 25 degrees C as a function of solution pH and ionic strength. We find that short-range protein interactions are influenced by water molecules strongly associated with a relatively small fraction of the protein surface. However, the effect of these strongly associated water molecules on the surface complementarity of short-range protein interactions is significant, and must be taken into account for an accurate description of B(2). We also observe remarkably similar hydration behavior for these proteins despite substantial differences in their three-dimensional structures and spatial charge distributions, suggesting a general characterization of protein hydration.

Dependence of Interaction Free Energy between Solutes on an External Electrostatic Field

PubMed Central

Yang, Pei-Kun

2013-01-01

To explore the athermal effect of an external electrostatic field on the stabilities of protein conformations and the binding affinities of protein-protein/ligand interactions, the dependences of the polar and hydrophobic interactions on the external electrostatic field, −Eext, were studied using molecular dynamics (MD) simulations. By decomposing Eext into, along, and perpendicular to the direction formed by the two solutes, the effect of Eext on the interactions between these two solutes can be estimated based on the effects from these two components. Eext was applied along the direction of the electric dipole formed by two solutes with opposite charges. The attractive interaction free energy between these two solutes decreased for solutes treated as point charges. In contrast, the attractive interaction free energy between these two solutes increased, as observed by MD simulations, for Eext = 40 or 60 MV/cm. Eext was applied perpendicular to the direction of the electric dipole formed by these two solutes. The attractive interaction free energy was increased for Eext = 100 MV/cm as a result of dielectric saturation. The force on the solutes along the direction of Eext computed from MD simulations was greater than that estimated from a continuum solvent in which the solutes were treated as point charges. To explore the hydrophobic interactions, Eext was applied to a water cluster containing two neutral solutes. The repulsive force between these solutes was decreased/increased for Eext along/perpendicular to the direction of the electric dipole formed by these two solutes. PMID:23852018

Theoretical studies of the mechanism of the action of the neurohypophyseal hormones. I. Molecular electrostatic potential (MEP) and molecular electrostatic field (MEF) maps of some vasopressin analogues

NASA Astrophysics Data System (ADS)

Liwo, Adam; Tempczyk, Anna; Grzonka, Zbigniew

1989-09-01

Continuing our theoretical studies of the oxytocin and vasopressin analogues, we have analysed the molecular electrostatic potential (MEP) and the norm of the molecular electrostatic field (MEF) of [1- β-mercaptopropionic acid]-arginine-vasopressin ([Mpa1]-AVP), [1-( β-mercapto- β,β-cyclopentamethylene)propionic acid]-arginine-vasopressin ([Cpp']-AVP), and [1-thiosalicylic acid]-arginine-vasopressin ([Ths']-AVP) whose low-energy conformations were calculated in our previous work. These compounds are known from experiment to exhibit different biological activity. The scalar fields mentioned determine the energy of interaction with either charged (MEP) or polar (MEF) species, the energy being in the second case either optimal or Boltzmann-averaged over all the possible orientations of the dipole moment versus the electrostatic field. The electrostatic interactions slowly vanish with distance and can therefore be considered to be the factor determining the molecular shape at greater distances, which can help in both predicting the interactions with the receptor at the stage of remote recognition and in finding the preferred directions of solvation by a polar solvent. In the analysis of the fields three techniques have been used: (i) the construction of maps in certain planes; (ii) the construction of maps on spheres centered in the charge center of the molecule under study and of poles chosen according to the main axes of the quadrupole moment; and (iii) the construction of surfaces corresponding to a given value of potential. The results obtained show that the shapes of both MEP and MEF are similar in the case of [Mpa1]-AVP and [Cpp1-AVP (biologically active), while some differences emerge when comparing these compounds with [Ths1]-AVP (inactive). It has also been found that both MEP and MEF depend even more strongly on conformation.

Accurate prediction of polarised high order electrostatic interactions for hydrogen bonded complexes using the machine learning method kriging.

PubMed

Hughes, Timothy J; Kandathil, Shaun M; Popelier, Paul L A

2015-02-05

As intermolecular interactions such as the hydrogen bond are electrostatic in origin, rigorous treatment of this term within force field methodologies should be mandatory. We present a method able of accurately reproducing such interactions for seven van der Waals complexes. It uses atomic multipole moments up to hexadecupole moment mapped to the positions of the nuclear coordinates by the machine learning method kriging. Models were built at three levels of theory: HF/6-31G(**), B3LYP/aug-cc-pVDZ and M06-2X/aug-cc-pVDZ. The quality of the kriging models was measured by their ability to predict the electrostatic interaction energy between atoms in external test examples for which the true energies are known. At all levels of theory, >90% of test cases for small van der Waals complexes were predicted within 1 kJ mol(-1), decreasing to 60-70% of test cases for larger base pair complexes. Models built on moments obtained at B3LYP and M06-2X level generally outperformed those at HF level. For all systems the individual interactions were predicted with a mean unsigned error of less than 1 kJ mol(-1). Copyright © 2013 Elsevier B.V. All rights reserved.

Theoretical assessment of the disparity in the electrostatic forces between two point charges and two conductive spheres of equal radii

NASA Astrophysics Data System (ADS)

Kolikov, Kiril

2016-11-01

The Coulomb's formula for the force FC of electrostatic interaction between two point charges is well known. In reality, however, interactions occur not between point charges, but between charged bodies of certain geometric form, size and physical structure. This leads to deviation of the estimated force FC from the real force F of electrostatic interaction, thus imposing the task to evaluate the disparity. In the present paper the problem is being solved theoretically for two charged conductive spheres of equal radii and arbitrary electric charges. Assessment of the deviation is given as a function of the ratio of the distance R between the spheres centers to the sum of their radii. For the purpose, relations between FC and F derived in a preceding work of ours, are employed to generalize the Coulomb's interactions. At relatively short distances between the spheres, the Coulomb force FC, as estimated to be induced by charges situated at the centers of the spheres, differ significantly from the real force F of interaction between the spheres. In the case of zero and non-zero charge we prove that with increasing the distance between the two spheres, the force F decrease rapidly, virtually to zero values, i.e. it appears to be short-acting force.

Electromagnetic theory of the nuclear interaction. Application to the deuteron {sup 2}H

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schaeffer, Bernard

2012-06-20

Bieler of the Rutherford laboratory imagined in 1924 a magnetic attraction equilibrating an electrostatic repulsion between the protons. Since the discovery of the neutron and the magnetic moments of the nucleons proving that the neutron contains electric charges, nobody, as far as I know, has tried to apply electromagnetism to the nuclear interaction. The electrostatic and magnetic interactions are completely neglected except for a mean Coulomb repulsion. As it is well known, there is an attraction between an electric charge and a neutral conductor. In the neutron, the positive charges are repelled and the negative charges attracted by a nearbymore » proton. There is a net attraction explaining quantitatively the so-called strong force as it is shown in this paper. In the deuteron, the magnetic repulsion equilibrates the electrostatically induced neutron-proton attraction. The experimental value (- 2.2 MeV) is surrounded by - 1.6 MeV and - 2.5 MeV, depending on the calculation method. No arbitrary fitting parameter is used, only physical constants: it is a true ab initio calculation. The theoretical ratio between nuclear and chemical energies has been found to be (m{sub p}/m{sub e}{alpha}), proving that the usual assumption that the electromagnetic interaction is too feeble to predict the nuclear interaction is incorrect.« less

Molecular Modeling of the Structural and Dynamical Changes in Calcium Channel TRPV5 Induced by the African-Specific A563T Variation.

PubMed

Wang, Lingyun; Holmes, Ross P; Peng, Ji-Bin

2016-03-01

Transient receptor potential cation channels, vanilloid subfamily, member 5 (TRPV5) plays a key role in active Ca(2+) reabsorption in the kidney. Variations in TRPV5 occur at high frequency in African populations and may contribute to their higher efficiency of Ca(2+) reabsorption. One of the African specific variations, A563T, exhibits increased Ca(2+) transport ability. However, it is unclear how this variation influences the channel pore. On the basis of the structure of TRPV1, a TRPV5 model was generated to simulate the structural and dynamical changes induced by the A563T variation. On the basis of this model, amino acid residue 563 interacts with V540, which is one residue away from the key residue, D542, involved in Ca(2+) selectivity and Mg(2+) blockade. The A563T variation increases secondary structure stability and reduces dynamical motion of D542. In addition, the A563T variation alters the electrostatic potential of the outer surface of the pore. Differences in contact between selective filter residues and residue 563 and in electrostatic potential between the two TRPV5 variants were also observed in another model derived from an alternative alignment in the selective filters between TRPV5 and TRPV1. These findings indicate that the A563T variation induces structural, dynamical, and electrostatic changes in the TRPV5 pore, providing structural insight into the functional alterations associated with the A563T variation.

Maintenance of electrostatic stabilization in altered tubulin lateral contacts may facilitate formation of helical filaments in foraminifera.

PubMed

Bassen, David M; Hou, Yubo; Bowser, Samuel S; Banavali, Nilesh K

2016-08-19

Microtubules in foraminiferan protists (forams) can convert into helical filament structures, in which longitudinal intraprotofilament interactions between tubulin heterodimers are thought to be lost, while lateral contacts across protofilaments are still maintained. The coarse geometric features of helical filaments are known through low-resolution negative stain electron microscopy (EM). In this study, geometric restraints derived from these experimental data were used to generate an average atomic-scale helical filament model, which anticipated a modest reorientation in the lateral tubulin heterodimer interface. Restrained molecular dynamics (MD) simulations of the nearest neighbor interactions combined with a Genalized Born implicit solvent model were used to assess the lateral, longitudinal, and seam contacts in 13-3 microtubules and the reoriented lateral contacts in the helical filament model. This electrostatic analysis suggests that the change in the lateral interface in the helical filament does not greatly diminish the lateral electrostatic interaction. After longitudinal dissociation, the 13-3 seam interaction is much weaker than the reoriented lateral interface in the helical filament model, providing a plausible atomic-detail explanation for seam-to-lateral contact transition that enables the transition to a helical filament structure.

Maintenance of electrostatic stabilization in altered tubulin lateral contacts may facilitate formation of helical filaments in foraminifera

NASA Astrophysics Data System (ADS)

Bassen, David M.; Hou, Yubo; Bowser, Samuel S.; Banavali, Nilesh K.

2016-08-01

Microtubules in foraminiferan protists (forams) can convert into helical filament structures, in which longitudinal intraprotofilament interactions between tubulin heterodimers are thought to be lost, while lateral contacts across protofilaments are still maintained. The coarse geometric features of helical filaments are known through low-resolution negative stain electron microscopy (EM). In this study, geometric restraints derived from these experimental data were used to generate an average atomic-scale helical filament model, which anticipated a modest reorientation in the lateral tubulin heterodimer interface. Restrained molecular dynamics (MD) simulations of the nearest neighbor interactions combined with a Genalized Born implicit solvent model were used to assess the lateral, longitudinal, and seam contacts in 13-3 microtubules and the reoriented lateral contacts in the helical filament model. This electrostatic analysis suggests that the change in the lateral interface in the helical filament does not greatly diminish the lateral electrostatic interaction. After longitudinal dissociation, the 13-3 seam interaction is much weaker than the reoriented lateral interface in the helical filament model, providing a plausible atomic-detail explanation for seam-to-lateral contact transition that enables the transition to a helical filament structure.

Comparative studies on group III σ-hole and π-hole interactions.

PubMed

Gao, Lei; Zeng, Yanli; Zhang, Xueying; Meng, Lingpeng

2016-05-30

The σ-hole of M2 H6 (M = Al, Ga, In) and π-hole of MH3 (M = Al, Ga, In) were discovered and analyzed, the bimolecular complexes M2 H6 ···NH3 and MH3 ···N2 P2 F4 (M = Al, Ga, In) were constructed to carry out comparative studies on the group III σ-hole interactions and π-hole interactions. The two types of interactions are all partial-covalent interactions; the π-hole interactions are stronger than σ-hole interactions. The electrostatic energy is the largest contribution for forming the σ-hole and π-hole interaction, the polarization energy is also an important factor to form the M···N interaction. The electrostatic energy contributions to the interaction energy of the σ-hole interactions are somewhat greater than those of the π-hole interactions. However, the polarization contributions for the π-hole interactions are somewhat greater than those for the σ-hole interactions. © 2016 Wiley Periodicals, Inc.

Teaching Ion-Ion, Ion-Dipole, and Dipole-Dipole Interactions

ERIC Educational Resources Information Center

Yoder, Claude H.

1977-01-01

Discusses how electrostatic interactions can be taught quantitatively through Coulomb's Law at a variety of points in a chemistry curriculum. Each type of interaction is shown at both the intramolecular and the inter-"molecular" levels. (MR)

Protecting Gram-negative bacterial cell envelopes from human lysozyme: Interactions with Ivy inhibitor proteins from Escherichia coli and Pseudomonas aeruginosa.

PubMed

Liu, Zhihong; García-Díaz, Beatriz; Catacchio, Bruno; Chiancone, Emilia; Vogel, Hans J

2015-11-01

Lysozymes play an important role in host defense by degrading peptidoglycan in the cell envelopes of pathogenic bacteria. Several Gram-negative bacteria can evade this mechanism by producing periplasmic proteins that inhibit the enzymatic activity of lysozyme. The Escherichia coli inhibitor of vertebrate lysozyme, Ivyc and its Pseudomonas aeruginosa homolog, Ivyp1 have been shown to be potent inhibitors of hen egg white lysozyme (HEWL). Since human lysozyme (HL) plays an important role in the innate immune response, we have examined the binding of HL to Ivyc and Ivyp1. Our results show that Ivyp1 is a weaker inhibitor of HL than Ivyc even though they inhibit HEWL with similar potency. Calorimetry experiments confirm that Ivyp1 interacts more weakly with HL than HEWL. Analytical ultracentrifugation studies revealed that Ivyp1 in solution is a monomer and forms a 30kDa heterodimer with both HL and HEWL, while Ivyc is a homodimer that forms a tetramer with both enzymes. The interaction of Ivyp1 with HL was further characterized by NMR chemical shift perturbation experiments. In addition to the characteristic His-containing Ivy inhibitory loop that binds into the active site of lysozyme, an extended loop (P2) between the final two beta-strands also participates in forming protein-protein interactions. The P2 loop is not conserved in Ivyc and it constitutes a flexible region in Ivyp1 that becomes more rigid in the complex with HL. We conclude that differences in the electrostatic interactions at the binding interface between Ivy inhibitors and distinct lysozymes determine the strength of this interaction. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides. Copyright © 2015 Elsevier B.V. All rights reserved.

Electrostatic potential of B-DNA: effect of interionic correlations.

PubMed Central

Gavryushov, S; Zielenkiewicz, P

1998-01-01

Modified Poisson-Boltzmann (MPB) equations have been numerically solved to study ionic distributions and mean electrostatic potentials around a macromolecule of arbitrarily complex shape and charge distribution. Results for DNA are compared with those obtained by classical Poisson-Boltzmann (PB) calculations. The comparisons were made for 1:1 and 2:1 electrolytes at ionic strengths up to 1 M. It is found that ion-image charge interactions and interionic correlations, which are neglected by the PB equation, have relatively weak effects on the electrostatic potential at charged groups of the DNA. The PB equation predicts errors in the long-range electrostatic part of the free energy that are only approximately 1.5 kJ/mol per nucleotide even in the case of an asymmetrical electrolyte. In contrast, the spatial correlations between ions drastically affect the electrostatic potential at significant separations from the macromolecule leading to a clearly predicted effect of charge overneutralization. PMID:9826596

Contribution of electrostatics to the binding of pancreatic-type ribonucleases to membranes.

PubMed

Sundlass, Nadia K; Eller, Chelcie H; Cui, Qiang; Raines, Ronald T

2013-09-17

Pancreatic-type ribonucleases show clinical promise as chemotherapeutic agents but are limited in efficacy by the inefficiency of their uptake by human cells. Cellular uptake can be increased by the addition of positive charges to the surface of ribonucleases, either by site-directed mutagenesis or by chemical modification. This observation has led to the hypothesis that ribonuclease uptake by cells depends on electrostatics. Here, we use a combination of experimental and computational methods to ascertain the contribution of electrostatics to the cellular uptake of ribonucleases. We focus on three homologous ribonucleases: Onconase (frog), ribonuclease A (cow), and ribonuclease 1 (human). Our results support the hypothesis that electrostatics are necessary for the cellular uptake of Onconase. In contrast, specific interactions with cell-surface components likely contribute more to the cellular uptake of ribonuclease A and ribonuclease 1 than do electrostatics. These findings provide insight for the design of new cytotoxic ribonucleases.

On the electrostatic and steric similarity of lactam compounds and the natural substrate for bacterial cell-wall biosynthesis

NASA Astrophysics Data System (ADS)

Frau, J.; Price, S. L.

1996-04-01

Electrostatic and structural properties of a set of β-lactam, γ-lactam and nonlactam compounds have been analyzed and compared with those of a model of the natural substrate d-alanyl- d-alanine for the carboxy- and transpeptidase enzymes. This first comparison of the electrostatic properties has been based on a distributed multipole analysis of high-quality ab initio wave functions of the substrate and potential antibiotics. The electrostatic similarity of the substrate and active compounds is apparent, and contrasts with the electrostatic properties of the noninhibitors. This has been quantified to give a reasonable correlation with the MIC (Minimum Concentration for Inhibition) and with kinetic data (k2/K) in accordance with the model for interaction of the lactam compounds with dd-peptidase. These correlations provide a better prediction of antibacterial activity than purely structural criteria.

DelPhiForce web server: electrostatic forces and energy calculations and visualization.

PubMed

Li, Lin; Jia, Zhe; Peng, Yunhui; Chakravorty, Arghya; Sun, Lexuan; Alexov, Emil

2017-11-15

Electrostatic force is an essential component of the total force acting between atoms and macromolecules. Therefore, accurate calculations of electrostatic forces are crucial for revealing the mechanisms of many biological processes. We developed a DelPhiForce web server to calculate and visualize the electrostatic forces at molecular level. DelPhiForce web server enables modeling of electrostatic forces on individual atoms, residues, domains and molecules, and generates an output that can be visualized by VMD software. Here we demonstrate the usage of the server for various biological problems including protein-cofactor, domain-domain, protein-protein, protein-DNA and protein-RNA interactions. The DelPhiForce web server is available at: http://compbio.clemson.edu/delphi-force. delphi@clemson.edu. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Energy decomposition analysis of the interactions in adduct ions of acetophenone and Na+, NH4+ and H+ in the gas phase

NASA Astrophysics Data System (ADS)

Sugimura, Natsuhiko; Igarashi, Yoko; Aoyama, Reiko; Shibue, Toshimichi

2017-09-01

The physical origins of the interactions in the acetophenone cation adducts [M+Na]+, [M+NH4]+, and [M+H]+ were explored by localized molecular orbital-energy decomposition analysis and density functional theory. The analyses highlighted the differences in the interactions in the three adduct ions. Electrostatic energy was important in [M+Na]+ and there was little change in the acetophenone orbital shape. Both electrostatic and polarization energy were important in [M+NH4]+, and a considerable change in the orbital shape occurred to maximize the strength of the hydrogen bond. Polarization energy was the major attractive force in [M+H]+.

Effects of electrostatic interactions on ligand dissociation kinetics

NASA Astrophysics Data System (ADS)

Erbaş, Aykut; de la Cruz, Monica Olvera; Marko, John F.

2018-02-01

We study unbinding of multivalent cationic ligands from oppositely charged polymeric binding sites sparsely grafted on a flat neutral substrate. Our molecular dynamics simulations are suggested by single-molecule studies of protein-DNA interactions. We consider univalent salt concentrations spanning roughly a 1000-fold range, together with various concentrations of excess ligands in solution. To reveal the ionic effects on unbinding kinetics of spontaneous and facilitated dissociation mechanisms, we treat electrostatic interactions both at a Debye-Hückel (DH) (or implicit ions, i.e., use of an electrostatic potential with a prescribed decay length) level and by the more precise approach of considering all ionic species explicitly in the simulations. We find that the DH approach systematically overestimates unbinding rates, relative to the calculations where all ion pairs are present explicitly in solution, although many aspects of the two types of calculation are qualitatively similar. For facilitated dissociation (FD) (acceleration of unbinding by free ligands in solution) explicit-ion simulations lead to unbinding at lower free-ligand concentrations. Our simulations predict a variety of FD regimes as a function of free-ligand and ion concentrations; a particularly interesting regime is at intermediate concentrations of ligands where nonelectrostatic binding strength controls FD. We conclude that explicit-ion electrostatic modeling is an essential component to quantitatively tackle problems in molecular ligand dissociation, including nucleic-acid-binding proteins.

FY04 LDRD Final Report: Interaction of Viruses with Membranes and Soil Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schaldach, C M

2005-02-08

The influence of ionic strength on the electrostatic interaction of viruses with environmentally relevant surfaces was determined for three viruses, MS2, Q{beta} and Norwalk. The environmental surface is modeled as charged Gouy-Chapman plane with and without a finite atomistic region (patch) of opposite charge. The virus is modeled as a particle comprised of ionizable amino acid residues in a shell surrounding a spherical RNA core of negative charge, these charges being compensated for by a Coulomb screening due to intercalated ions. Surface potential calculations for each of the viruses show excellent agreement with electrophoretic mobility and zeta potential measurements asmore » a function of pH. The results indicate that the electrostatic interaction between the virus and the planar surface, mitigated by the ionic strength of the solute, is dependent upon the spatial distribution of the amino acid residues in the different viruses. Specifically, the order of interaction energies with the patch (MS2 greatest at 5 mM; Norwalk greatest at 20 mM) is dependent upon the ionic strength of the fluid as a direct result of the viral coat amino acid distributions. We have developed an atomistic-scale method of calculation of the binding energy of viruses to surfaces including electrostatic, van der Waals, electron-overlap repulsion, surface charge polarization (images), and hydrophobic effects. The surface is treated as a Gouy-Chapman plane allowing inclusion of pH and ionic strength effects on the electrostatic potential at each amino acid charge. Van der Waals parameters are obtained from the DREIDING force field and from Hamaker constant measurements. We applied this method to the calculation of the Cowpea Mosaic Virus (CPMV), a negatively charged virus at a pH of 7.0, and find that the viral-gold surface interaction is very long range for both signs of surface potential, a result due to the electrostatic forces. For a negative (Au) surface potential of -0.05 volts, a nearly 4 eV barrier must be overcome to reach 1 nm from the surface.« less

VASP-E: Specificity Annotation with a Volumetric Analysis of Electrostatic Isopotentials

PubMed Central

Chen, Brian Y.

2014-01-01

Algorithms for comparing protein structure are frequently used for function annotation. By searching for subtle similarities among very different proteins, these algorithms can identify remote homologs with similar biological functions. In contrast, few comparison algorithms focus on specificity annotation, where the identification of subtle differences among very similar proteins can assist in finding small structural variations that create differences in binding specificity. Few specificity annotation methods consider electrostatic fields, which play a critical role in molecular recognition. To fill this gap, this paper describes VASP-E (Volumetric Analysis of Surface Properties with Electrostatics), a novel volumetric comparison tool based on the electrostatic comparison of protein-ligand and protein-protein binding sites. VASP-E exploits the central observation that three dimensional solids can be used to fully represent and compare both electrostatic isopotentials and molecular surfaces. With this integrated representation, VASP-E is able to dissect the electrostatic environments of protein-ligand and protein-protein binding interfaces, identifying individual amino acids that have an electrostatic influence on binding specificity. VASP-E was used to examine a nonredundant subset of the serine and cysteine proteases as well as the barnase-barstar and Rap1a-raf complexes. Based on amino acids established by various experimental studies to have an electrostatic influence on binding specificity, VASP-E identified electrostatically influential amino acids with 100% precision and 83.3% recall. We also show that VASP-E can accurately classify closely related ligand binding cavities into groups with different binding preferences. These results suggest that VASP-E should prove a useful tool for the characterization of specific binding and the engineering of binding preferences in proteins. PMID:25166865

Experimental detection of long-distance interactions between biomolecules through their diffusion behavior: numerical study.

PubMed

Nardecchia, Ilaria; Spinelli, Lionel; Preto, Jordane; Gori, Matteo; Floriani, Elena; Jaeger, Sebastien; Ferrier, Pierre; Pettini, Marco

2014-08-01

The dynamical properties and diffusive behavior of a collection of mutually interacting particles are numerically investigated for two types of long-range interparticle interactions: Coulomb-electrostatic and dipole-electrodynamic. It is shown that when the particles are uniformly distributed throughout the accessible space, the self-diffusion coefficient is always lowered by the considered interparticle interactions, irrespective of their attractive or repulsive character. This fact is also confirmed by a simple model to compute the correction to the Brownian diffusion coefficient due to the interactions among the particles. These interactions are also responsible for the onset of dynamical chaos and an associated chaotic diffusion which still follows an Einstein-Fick-like law for the mean-square displacement as a function of time. Transitional phenomena are observed for Coulomb-electrostatic (repulsive) and dipole-electrodynamic (attractive) interactions considered both separately and in competition. The outcomes reported in this paper clearly indicate a feasible experimental method to probe the activation of resonant electrodynamic interactions among biomolecules.

An ionic-chemical-mechanical model for muscle contraction.

PubMed

Manning, Gerald S

2016-12-01

The dynamic process underlying muscle contraction is the parallel sliding of thin actin filaments along an immobile thick myosin fiber powered by oar-like movements of protruding myosin cross bridges (myosin heads). The free energy for functioning of the myosin nanomotor comes from the hydrolysis of ATP bound to the myosin heads. The unit step of translational movement is based on a mechanical-chemical cycle involving ATP binding to myosin, hydrolysis of the bound ATP with ultimate release of the hydrolysis products, stress-generating conformational changes in the myosin cross bridge, and relief of built-up stress in the myosin power stroke. The cycle is regulated by a transition between weak and strong actin-myosin binding affinities. The dissociation of the weakly bound complex by addition of salt indicates the electrostatic basis for the weak affinity, while structural studies demonstrate that electrostatic interactions among negatively charged amino acid residues of actin and positively charged residues of myosin are involved in the strong binding interface. We therefore conjecture that intermediate states of increasing actin-myosin engagement during the weak-to-strong binding transition also involve electrostatic interactions. Methods of polymer solution physics have shown that the thin actin filament can be regarded in some of its aspects as a net negatively charged polyelectrolyte. Here we employ polyelectrolyte theory to suggest how actin-myosin electrostatic interactions might be of significance in the intermediate stages of binding, ensuring an engaged power stroke of the myosin motor that transmits force to the actin filament, and preventing the motor from getting stuck in a metastable pre-power stroke state. We provide electrostatic force estimates that are in the pN range known to operate in the cycle. © 2016 Wiley Periodicals, Inc.

Intermolecular Interactions and Electrostatic Properties of the [beta]-Hydroquinone Apohost: Implications for Supramolecular Chemistry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clausen, Henrik F.; Chen, Yu-Sheng; Jayatilaka, Dylan

2012-02-07

The crystal structure of the {beta}-polymorph of hydroquinone ({beta}-HQ), the apohost of a large family of clathrates, is reported with a specific focus on intermolecular interactions and the electrostatic nature of its cavity. Hirshfeld surface analysis reveals subtle close contacts between two interconnecting HQ networks, and the local packing and related close contacts were examined by breakdown of the fingerprint plot. An experimental multipole model containing anisotropic thermal parameters for hydrogen atoms has been successfully refined against 15(2) K single microcrystal synchrotron X-ray diffraction data. The experimental electron density model has been compared with a theoretical electron density calculated withmore » the molecule embedded in its own crystal field. Hirshfeld charges, interaction energies and the electrostatic potential calculated for both models are qualitatively in good agreement, but small differences in the electrostatic potential persist due to charge transfer from all hydrogen atoms to the oxygen atoms in the theoretical model. The electrostatic potential in the center of the cavity is positive, very shallow and highly symmetric, suggesting that the inclusion of polar molecules in the void will involve a balance between opposing effects. The electric field is by symmetry zero in the center of the cavity, increasing to a value of 0.0185 e/{angstrom}{sup 2} (0.27 V/{angstrom}) 1 {angstrom} along the 3-fold axis and 0.0105 e/{angstrom}{sup 2} (0.15 V/{angstrom}) 1 {angstrom} along the perpendicular direction. While these values are substantial in a macroscopic context, they are quite small for a molecular cavity and are not expected to strongly polarize a guest molecule.« less

Electronic-property dependent interactions between tetracycline and graphene nanomaterials in aqueous solution.

PubMed

He, Lin; Liu, Fei-Fei; Zhao, Mengyao; Qi, Zhen; Sun, Xuefei; Afzal, Muhammad Zaheer; Sun, Xiaomin; Li, Yanhui; Hao, Jingcheng; Wang, Shuguang

2018-04-01

Understanding the interactions between graphene nanomaterials (GNMs) and antibiotics in aqueous solution is critical to both the engineering applications of GNMs and the assessment of their potential impact on the fate and transport of antibiotics in the aquatic environment. In this study, adsorption of one common antibiotic, tetracycline, by graphene oxide (GO) and reduced graphene oxide (RGO) was examined with multi-walled carbon nanotubes (MWCNTs) and graphite as comparison. The results showed that the tetracycline adsorption capacity by the four selected carbonaceous materials on the unit mass basis followed an order of GO>RGO>MWCNTs>graphite. Upon normalization by surface area, graphite, RGO and MWCNTs had almost the same high tetracycline adsorption affinity while GO exhibited the lowest. We proposed π-electron-property dependent interaction mechanisms to explain the observed different adsorption behaviors. Density functional theory (DFT) calculations suggested that the oxygen-containing functional groups on GO surface reduced its π-electron-donating ability, and thus decreased the π-based interactions between tetracycline and GO surface. Comparison of adsorption efficiency at different pH indicated that electrostatic interaction also played an important role in tetracycline-GO interactions. Site energy analysis confirmed a highly heterogeneous distribution of the binding sites and strong tetracycline binding affinity of GO surface. Copyright © 2017. Published by Elsevier B.V.

In vitro evaluation of thiolated polydimethylaminoethylmethacrylate hydrogel sub-microparticles for oral insulin delivery.

PubMed

Sonia, T A; Sharma, Chandra P

2013-04-01

In this investigation, novel cationic thiomer, Thiolated polydimethylaminoethylmethacrylate (PDCys) is synthesised and the feasibility of PDCys sub-microparticles as oral insulin delivery carriers is evaluated in vitro. The presence of both positive charge and thiol group in the same matrix plays a vital role in improving the paracellular permeability. Thiol groups interacts with cysteine rich subdomains via disulfide bond formation and positive charge interacts with sialic residues of mucus glycoproteins via electrostatic interaction, thereby increasing the mucoadhesivity. Cytotoxic evaluation by MTT assay shows that PDCys is nontoxic. Force and Work of adhesion of PDCys was found found to be higher than that of parent polymer. ELISA and Circular dichroism spectra confirms that PDCys retains the biological activity and conformation of insulin. Moreover, PDCys is capable of opening the tight junctions by actin and occludin filament dislocation. Furthermore, permeation of FD4 on Caco-2 cells is improved by 3.9 fold compared to the parent polymer. Preliminary studies suggest that thiolated particles can serve as potential vehicles for oral insulin delivery.

Effects of molecular model, ionic strength, divalent ions, and hydrophobic interaction on human neurofilament conformation

NASA Astrophysics Data System (ADS)

Lee, Joonseong; Kim, Seonghoon; Chang, Rakwoo; Jayanthi, Lakshmi; Gebremichael, Yeshitila

2013-01-01

The present study examines the effects of the model dependence, ionic strength, divalent ions, and hydrophobic interaction on the structural organization of the human neurofilament (NF) brush, using canonical ensemble Monte Carlo (MC) simulations of a coarse-grained model with the amino-acid resolution. The model simplifies the interactions between the NF core and the sidearm or between the sidearms by the sum of excluded volume, electrostatic, and hydrophobic interactions, where both monovalent salt ions and solvents are implicitly incorporated into the electrostatic interaction potential. Several important observations are made from the MC simulations of the coarse-grained model NF systems. First, the mean-field type description of monovalent salt ions works reasonably well in the NF system. Second, the manner by which the NF sidearms are arranged on the surface of the NF backbone core has little influence on the lateral extension of NF sidearms. Third, the lateral extension of the NF sidearms is highly affected by the ionic strength of the system: at low ionic strength, NF-M is most extended but at high ionic strength, NF-H is more stretched out because of the effective screening of the electrostatic interaction. Fourth, the presence of Ca2 + ions induces the attraction between negatively charged residues, which leads to the contraction of the overall NF extension. Finally, the introduction of hydrophobic interaction does not change the general structural organization of the NF sidearms except that the overall extension is contracted.

Potential effect of cationic liposomes on interactions with oral bacterial cells and biofilms.

PubMed

Sugano, Marika; Morisaki, Hirobumi; Negishi, Yoichi; Endo-Takahashi, Yoko; Kuwata, Hirotaka; Miyazaki, Takashi; Yamamoto, Matsuo

2016-01-01

Although oral infectious diseases have been attributed to bacteria, drug treatments remain ineffective because bacteria and their products exist as biofilms. Cationic liposomes have been suggested to electrostatically interact with the negative charge on the bacterial surface, thereby improving the effects of conventional drug therapies. However, the electrostatic interaction between oral bacteria and cationic liposomes has not yet been examined in detail. The aim of the present study was to examine the behavior of cationic liposomes and Streptococcus mutans in planktonic cells and biofilms. Liposomes with or without cationic lipid were prepared using a reverse-phase evaporation method. The zeta potentials of conventional liposomes (without cationic lipid) and cationic liposomes were -13 and 8 mV, respectively, and both had a mean particle size of approximately 180 nm. We first assessed the interaction between liposomes and planktonic bacterial cells with a flow cytometer. We then used a surface plasmon resonance method to examine the binding of liposomes to biofilms. We confirmed the binding behavior of liposomes with biofilms using confocal laser scanning microscopy. The interactions between cationic liposomes and S. mutans cells and biofilms were stronger than those of conventional liposomes. Microscopic observations revealed that many cationic liposomes interacted with the bacterial mass and penetrated the deep layers of biofilms. In this study, we demonstrated that cationic liposomes had higher affinity not only to oral bacterial cells, but also biofilms than conventional liposomes. This electrostatic interaction may be useful as a potential drug delivery system to biofilms.

Manipulation and Investigation of Uniformly-Spaced Nanowire Array on a Substrate via Dielectrophoresis and Electrostatic Interaction.

PubMed

Choi, U Hyeok; Park, Ji Hun; Kim, Jaekyun

2018-06-21

Directed-assembly of nanowires on the dielectrics-covered parallel electrode structure is capable of producing uniformly-spaced nanowire array at the electrode gap due to dielectrophoretic nanowire attraction and electrostatic nanowire repulsion. Beyond uniformly-spaced nanowire array formation, the control of spacing in the array is beneficial in that it should be the experimental basis of the precise positioning of functional nanowires on a circuit. Here, we investigate the material parameters and bias conditions to modulate the nanowire spacing in the ordered array, where the nanowire array formation is readily attained due to the electrostatic nanowire interaction. A theoretical model for the force calculation and the simulation of the induced charge in the assembled nanowire verifies that the longer nanowires on thicker dielectric layer tend to be assembled with a larger pitch due to the stronger nanowire-nanowire electrostatic repulsion, which is consistent with the experimental results. It was claimed that the stronger dielectrophoretic force is likely to attract more nanowires that are suspended in solution at the electrode gap, causing them to be less-spaced. Thus, we propose a generic mechanism, competition of dielectrophoretic and electrostatic force, to determine the nanowire pitch in an ordered array. Furthermore, this spacing-controlled nanowire array offers a way to fabricate the high-density nanodevice array without nanowire registration.

Solar wind interaction with dusty plasmas produces instabilities and solitary structures

NASA Astrophysics Data System (ADS)

Saleem, H.; Ali, S.

2017-12-01

It is pointed out that the solar wind interaction with dusty magnetospheres of the planets can give rise to purely growing instabilities as well as nonlinear electric field structures. Linear dispersion relation of the low frequency electrostatic ion-acoustic wave (IAW) is modified in the presence of stationary dust and its frequency becomes larger than its frequency in usual electron ion plasma even if ion temperature is equal to the electron temperature. This dust-ion-acoustic wave (DIAW) either becomes a purely growing electrostatic instability or turns out to be the modified dust-ion-acoustic wave (mDIAW) depending upon the magnitude of shear flow scale length and its direction. Growth rate of shear flow-driven electrostatic instability in a plasma having negatively charged stationary dust is larger than the usual D'Angelo instability of electron-ion plasma. It is shown that shear modified dust ion acoustic wave (mDIAW) produces electrostatic solitons in the nonlinear regime. The fluid theory predicts the existence of electrostatic solitons in the dusty plasmas in those regions where the inhomogeneous solar wind flow is parallel to the planetary or cometary magnetic field lines. The amplitude and width of the solitary structure depends upon dust density and magnitude of shear in the flow. This is a general theoretical model which is applied to dusty plasma of Saturn's F-ring for illustration.

Electrostatic wrapping of doxorubicin with curdlan to construct an efficient pH-responsive drug delivery system

NASA Astrophysics Data System (ADS)

Zhou, Jiang-Ling; Song, Fei; Tian, Jia-Feng; Nie, Wu-Cheng; Wang, Xiu-Li; Wang, Yu-Zhong

2017-07-01

The development of environmentally responsive drug delivery systems for the treatment of cancer has attracted particular interest in recent years. However, the enhancement of drug loading capacity and realization of pH-responsive drug delivery remain challenging. Herein, we employ carboxymethyl curdlan as a hydrophilic carrier to wrap doxorubicin (DOX) directly via electrostatic interaction. The sizes of the formed nanoparticles can be simply tuned by changing their feeding ratios. In particular, the nanoparticles are highly stable in aqueous solution without size variation. In vitro drug release and cytotoxicity assays illustrate that this delivery system can release DOX differentially under various environmental conditions and transport it into cell nuclei efficiently, with comparable therapeutic effect to the free drug. These results suggest that the carrying of antitumor drugs by polysaccharide via electrostatic interaction is a simple but effective way to construct a pH-dependent drug delivery platform.

Electrostatics-Driven Hierarchical Buckling of Charged Flexible Ribbons.

PubMed

Yao, Zhenwei; Olvera de la Cruz, Monica

2016-04-08

We investigate the rich morphologies of an electrically charged flexible ribbon, which is a prototype for many beltlike structures in biology and nanomaterials. Long-range electrostatic repulsion is found to govern the hierarchical buckling of the ribbon from its initially flat shape to its undulated and out-of-plane twisted conformations. In this process, the screening length is the key controlling parameter, suggesting that a convenient way to manipulate the ribbon morphology is simply to change the salt concentration. We find that these shapes originate from the geometric effect of the electrostatic interaction, which fundamentally changes the metric over the ribbon surface. We also identify the basic modes by which the ribbon reshapes itself in order to lower the energy. The geometric effect of the physical interaction revealed in this Letter has implications for the shape design of extensive ribbonlike materials in nano- and biomaterials.

Helical Structure Determines Different Susceptibilities of dsDNA, dsRNA, and tsDNA to Counterion-Induced Condensation

PubMed Central

Kornyshev, Alexei A.; Leikin, Sergey

2013-01-01

Recent studies of counterion-induced condensation of nucleic acid helices into aggregates produced several puzzling observations. For instance, trivalent cobalt hexamine ions condensed double-stranded (ds) DNA oligomers but not their more highly charged dsRNA counterparts. Divalent alkaline earth metal ions condensed triple-stranded (ts) DNA oligomers but not dsDNA. Here we show that these counterintuitive experimental results can be rationalized within the electrostatic zipper model of interactions between molecules with helical charge motifs. We report statistical mechanical calculations that reveal dramatic and nontrivial interplay between the effects of helical structure and thermal fluctuations on electrostatic interaction between oligomeric nucleic acids. Combining predictions for oligomeric and much longer helices, we also interpret recent experimental studies of the role of counterion charge, structure, and chemistry. We argue that an electrostatic zipper attraction might be a major or even dominant force in nucleic acid condensation. PMID:23663846

Study of the electrostatic effects of mutations on the surface of dehaloperoxidase-hemoglobin A.

PubMed

Zhao, Junjie; Rowe, Jennifer; Franzen, Jocelyn; He, Chi; Franzen, Stefan

2012-04-20

Point mutations of dehaloperoxidase-hemoglobin A (DHP A) that affect the surface charge have been prepared to study the interaction between DHP A with its substrate 2,4,6-trichlorophenol (TCP). Kinetic studies of these surface mutations showed a correlation, in which the more positively charged mutants have increased catalytic efficiency compared with wild type DHP A. As a result, the hypothesis of this study is that there is a global electrostatic interaction between DHP A and TCP. The electrostatic nature of substrate binding was further confirmed by the result that kinetic assays of DHP A were affected by ionic strength. Furthermore, isoelectric focusing (IEF) gel study showed that the pI-6.8 for DHP A, which indicates that DHP A has a slight negative charge pH 7, consistent with the kinetic observations. Copyright © 2012 Elsevier Inc. All rights reserved.

Electrostatic-Assisted Liquefaction of Porous Carbons

DOE PAGES

Li, Peipei; Schott, Jennifer A.; Zhang, Jinshui; ...

2017-10-10

Porous liquids are a newly developed porous material that combine unique fluidity with permanent porosity, which exhibit promising functionalities for a variety of applications. However, the apparent incompatibility between fluidity and permanent porosity makes the stabilization of porous nanoparticle with still empty pores in the dense liquid phase a significant challenging. For this study, by exploiting the electrostatic interaction between carbon networks and polymerized ionic liquids, we demonstrate that carbon-based porous nanoarchitectures can be well stabilized in liquids to afford permanent porosity, and thus opens up a new approach to prepare porous carbon liquids. Furthermore, we hope this facile synthesismore » strategy can be widely applicated to fabricate other types of porous liquids, such as those (e.g., carbon nitride, boron nitride, metal–organic frameworks, covalent organic frameworks etc.) also having the electrostatic interaction with polymerized ionic liquids, evidently advancing the development and understanding of porous liquids.« less

Coarse-graining, Electrostatics and pH effects in phospholipid systems

NASA Astrophysics Data System (ADS)

Travesset, Alex; Vangaveti, Sweta

2010-03-01

We introduce a minimal free energy describing the interaction of charged groups and counterions including both classical electrostatic and specific interactions. The predictions of the model are compared against the standard model for describing ions next to charged interfaces, consisting of Poisson-Boltzmann theory with additional constants describing ion binding, which are specific to the counterion and the interfacial charge (``chemical binding''). It is shown that the ``chemical'' model can be appropriately described by an underlying ``physical'' model over several decades in concentration, but the extracted binding constants are not uniquely defined, as they differ depending on the particular observable quantity being studied. It is also shown that electrostatic correlations for divalent (or higher valence) ions enhance the surface charge by increasing deprotonation, an effect not properly accounted within chemical models. The model is applied to the charged phospholipids phosphatidylserine, Phosphatidc acid and Phosphoinositides and implications for different biological processes are discussed.

Interaction forces between DPPC bilayers on glass

PubMed Central

Orozco-Alcaraz, Raquel; Kuhl, Tonya L.

2013-01-01

The Surface Force Apparatus (SFA) was utilized to obtain force-distance profiles between silica supported membranes formed by Langmuir-Blodgett deposition of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). In the absence of a membrane, a long range electrostatic and short range steric repulsion is measured due to deprotonation of silica in water and roughness of the silica film. The electrostatic repulsion is partially screened by the lipid membrane and a van der Waals adhesion comparable to that measured with well packed DPPC membranes on mica is measured. This finding suggest that electrostatic interactions due to the underlying negatively charged silica are likely present in other systems of glass supported membranes. In contrast, the charge of an underlying mica substrate is almost completely screened when a lipid membrane is deposited on the mica. The difference in the two systems is attributed to stronger physisorption of zwitterionic lipids to molecularly smooth mica compared to rougher silica. PMID:23199333

Origin of translocation barriers for polyelectrolyte chains.

PubMed

Kumar, Rajeev; Muthukumar, M

2009-11-21

For single-file translocations of a charged macromolecule through a narrow pore, the crucial step of arrival of an end at the pore suffers from free energy barriers, arising from changes in intrachain electrostatic interaction, distribution of ionic clouds and solvent molecules, and conformational entropy of the chain. All contributing factors to the barrier in the initial stage of translocation are evaluated by using the self-consistent field theory for the polyelectrolyte and the coupled Poisson-Boltzmann description for ions without radial symmetry. The barrier is found to be essentially entropic due to conformational changes. For moderate and high salt concentrations, the barriers for the polyelectrolyte chain are quantitatively equivalent to that of uncharged self-avoiding walks. Electrostatic effects are shown to increase the free energy barriers, but only slightly. The degree of ionization, electrostatic interaction strength, decreasing salt concentration, and the solvent quality all result in increases in the barrier.

QM/MM hybrid calculation of biological macromolecules using a new interface program connecting QM and MM engines

NASA Astrophysics Data System (ADS)

Hagiwara, Yohsuke; Ohta, Takehiro; Tateno, Masaru

2009-02-01

An interface program connecting a quantum mechanics (QM) calculation engine, GAMESS, and a molecular mechanics (MM) calculation engine, AMBER, has been developed for QM/MM hybrid calculations. A protein-DNA complex is used as a test system to investigate the following two types of QM/MM schemes. In a 'subtractive' scheme, electrostatic interactions between QM/MM regions are truncated in QM calculations; in an 'additive' scheme, long-range electrostatic interactions within a cut-off distance from QM regions are introduced into one-electron integration terms of a QM Hamiltonian. In these calculations, 338 atoms are assigned as QM atoms using Hartree-Fock (HF)/density functional theory (DFT) hybrid all-electron calculations. By comparing the results of the additive and subtractive schemes, it is found that electronic structures are perturbed significantly by the introduction of MM partial charges surrounding QM regions, suggesting that biological processes occurring in functional sites are modulated by the surrounding structures. This also indicates that the effects of long-range electrostatic interactions involved in the QM Hamiltonian are crucial for accurate descriptions of electronic structures of biological macromolecules.

Binding interactions of halogenated bisphenol A with mouse PPARα: In vitro investigation and molecular dynamics simulation.

PubMed

Zhang, Jie; Li, Tiezhu; Wang, Tuoyi; Guan, Tianzhu; Yu, Hansong; Li, Zhuolin; Wang, Yongzhi; Wang, Yongjun; Zhang, Tiehua

2018-02-01

The binding of bisphenol A (BPA) and its halogenated derivatives (halogenated BPAs) to mouse peroxisome proliferator-activated receptor α ligand binding domain (mPPARα-LBD) was examined by a combination of in vitro investigation and in silico simulation. Fluorescence polarization (FP) assay showed that halogenated BPAs could bind to mPPARα-LBD* as the affinity ligands. The calculated electrostatic potential (ESP) illustrated the different charge distributions of halogenated BPAs with altered halogenation patterns. As electron-attracting substituents, halogens decrease the positive electrostatic potential and thereby have a significant influence on the electrostatic interactions of halogenated BPAs with mPPARα-LBD*. The docking results elucidated that hydrophobic and hydrogen-bonding interactions may also contribute to stabilize the binding of the halogenated BPAs to their receptor molecule. Comparison of the calculated binding energies with the experimentally determined affinities yielded a good correlation (R 2 =0.6659) that could provide a rational basis for designing environmentally benign chemicals with reduced toxicities. This work can potentially be used for preliminary screening of halogenated BPAs. Copyright © 2017 Elsevier B.V. All rights reserved.

Electrostatic stabilization in sperm whale and harbor seal myoglobins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gurd, F.R.N.; Friend, S.H.; Rothgeb, T.M.

1980-10-01

The compact, largely helical structure of sperm whale and harbor seal myoglobins undergoes an abrupt one-step transition between pH 4.5 and 3.5 as monitored by changes in either the heme Soret band absorbance or circular dichroism probes of secondary structure, for which a modified Tanford-Kirkwood theory provides identification of certain dominant electrostatic interactions responsible for the loss of stability. A similar treatment permits identification of the electrostatic interactions primarily responsible for a process in which the anchoring of the A helix to other parts of the molecule is weakened. This process is detected with both myoglobins, in a pH rangemore » approx. 1 unit higher than the onset of the overall unfolding process, through changes in the circular dichroic spectra near 295 nm which correspond to the L/sub a/O-O band of the only two tryptophan residues in these proteins, residues 7 and 14. In each case protonation of certain sites in neighboring parts of the molecule can be identified as producing destabilizing interactions with components of the A helix, particularly with lysine 16.« less

Counterion effects in protein nanoparticle electrostatic binding: a theoretical study.

PubMed

Ghosh, Goutam

2015-04-01

Effects of counterions on the folding conformation of proteins, bound electrostatically on the surface of charge-ligand functionalized nanoparticles, have been investigated based on the protein folding energy calculation. The folding energy of a protein has been taken as a sum of the short range interaction energies, like, the van der Waals attraction and the hydrogen bond energies, and the long range coulomb interaction energy. On electrostatic binding, counterions associated with surface ligands of nanoparticles diffuse into bound proteins through the medium of dispersion. As a result, bound proteins partially unfold, as observed in circular dichroism experiments, which has been realized using the "charge-dipole" and the "charge-induced dipole" interactions of counterions with polar and non-polar residues, respectively. The effect of counterions solvation in the dispersing medium, e.g., water, which causes water molecules to polarize around the counterions, has also been considered. The folding energy of bound proteins has been seen to decrease proportionally with the increasing number of diffusion of counterions and their polarizability. Copyright © 2015 Elsevier B.V. All rights reserved.

Surface charge accumulation of particles containing radionuclides in open air.

PubMed

Kim, Yong-Ha; Yiacoumi, Sotira; Tsouris, Costas

2015-05-01

Radioactivity can induce charge accumulation on radioactive particles. However, electrostatic interactions caused by radioactivity are typically neglected in transport modeling of radioactive plumes because it is assumed that ionizing radiation leads to charge neutralization. The assumption that electrostatic interactions caused by radioactivity are negligible is evaluated here by examining charge accumulation and neutralization on particles containing radionuclides in open air. A charge-balance model is employed to predict charge accumulation on radioactive particles. It is shown that particles containing short-lived radionuclides can be charged with multiple elementary charges through radioactive decay. The presence of radioactive particles can significantly modify the particle charge distribution in open air and yield an asymmetric bimodal charge distribution, suggesting that strong electrostatic particle interactions may occur during short- and long-range transport of radioactive particles. Possible effects of transported radioactive particles on electrical properties of the local atmosphere are reported. The study offers insight into transport characteristics of airborne radionuclides. Results are useful in atmospheric transport modeling of radioactive plumes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modulation of electrostatic interactions to reveal a reaction network unifying the aggregation behaviour of the Aβ42 peptide and its variants† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc00215g Click here for additional data file.

PubMed Central

Meisl, Georg; Yang, Xiaoting

2017-01-01

The aggregation of the amyloid β peptide (Aβ42), which is linked to Alzheimer's disease, can be altered significantly by modulations of the peptide's intermolecular electrostatic interactions. Variations in sequence and solution conditions have been found to lead to highly variable aggregation behaviour. Here we modulate systematically the electrostatic interactions governing the aggregation kinetics by varying the ionic strength of the solution. We find that changes in the solution ionic strength induce a switch in the reaction pathway, altering the dominant mechanisms of aggregate multiplication. This strategy thereby allows us to continuously sample a large space of different reaction mechanisms and develop a minimal reaction network that unifies the experimental kinetics under a wide range of different conditions. More generally, this universal reaction network connects previously separate systems, such as charge mutants of the Aβ42 peptide, on a continuous mechanistic landscape, providing a unified picture of the aggregation mechanism of Aβ42. PMID:28979758

SMPBS: Web server for computing biomolecular electrostatics using finite element solvers of size modified Poisson-Boltzmann equation.

PubMed

Xie, Yang; Ying, Jinyong; Xie, Dexuan

2017-03-30

SMPBS (Size Modified Poisson-Boltzmann Solvers) is a web server for computing biomolecular electrostatics using finite element solvers of the size modified Poisson-Boltzmann equation (SMPBE). SMPBE not only reflects ionic size effects but also includes the classic Poisson-Boltzmann equation (PBE) as a special case. Thus, its web server is expected to have a broader range of applications than a PBE web server. SMPBS is designed with a dynamic, mobile-friendly user interface, and features easily accessible help text, asynchronous data submission, and an interactive, hardware-accelerated molecular visualization viewer based on the 3Dmol.js library. In particular, the viewer allows computed electrostatics to be directly mapped onto an irregular triangular mesh of a molecular surface. Due to this functionality and the fast SMPBE finite element solvers, the web server is very efficient in the calculation and visualization of electrostatics. In addition, SMPBE is reconstructed using a new objective electrostatic free energy, clearly showing that the electrostatics and ionic concentrations predicted by SMPBE are optimal in the sense of minimizing the objective electrostatic free energy. SMPBS is available at the URL: smpbs.math.uwm.edu © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Targeting EphA2-Sam and Its Interactome: Design and Evaluation of Helical Peptides Enriched in Charged Residues.

PubMed

Mercurio, Flavia A; Marasco, Daniela; Di Natale, Concetta; Pirone, Luciano; Costantini, Susan; Pedone, Emilia M; Leone, Marilisa

2016-11-17

The EphA2 receptor controls diverse physiological and pathological conditions and its levels are often upregulated in cancer. Targeting receptor overexpression, through modulation of endocytosis and consequent degradation, appears to be an appealing strategy for attacking tumor malignancy. In this scenario, the Sam domain of EphA2 plays a pivotal role because it is the site where protein regulators of endocytosis and stability are recruited by means of heterotypic Sam-Sam interactions. Because EphA2-Sam heterotypic complexes are largely based on electrostatic contacts, we have investigated the possibility of attacking these interactions with helical peptides enriched in charged residues. Several peptide sequences with high predicted helical propensities were designed, and detailed conformational analyses were conducted by diverse techniques including NMR, CD, and molecular dynamics (MD) simulations. Interaction studies were also performed by NMR, surface plasmon resonance (SPR), and microscale thermophoresis (MST) and led to the identification of two peptides capable of binding to the first Sam domain of Odin. These molecules represent early candidates for the generation of efficient Sam domain binders and antagonists of Sam-Sam interactions involving EphA2. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The existence of electron-acoustic shock waves and their interactions in a non-Maxwellian plasma with q-nonextensive distributed electrons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Jiu-Ning; He, Yong-Lin; Han, Zhen-Hai

2013-07-15

We present a theoretical investigation for the nonlinear interaction between electron-acoustic shock waves in a nonextensive two-electron plasma. The interaction is governed by a pair of Korteweg-de Vries-Burgers equations. We focus on studying the colliding effects on the propagation of shock waves, more specifically, we have studied the effects of plasma parameters, i.e., the nonextensive parameter q, the “hot” to “cold” electron number density ratio α, and the normalized electron kinematic viscosity η{sub 0} on the trajectory changes (phase shifts) of shock waves. It is found that there are trajectory changes (phase shifts) for both colliding shock waves in themore » present plasma system. We also noted that the nonlinearity has no decisive effect on the trajectory changes, the occurrence of trajectory changes may be due to the combined role played by the dispersion and dissipation of the nonlinear structure. Our theoretical study may be beneficial to understand the propagation and interaction of nonlinear electrostatic waves and may brings a possibility to develop the nonlinear theory of electron-acoustic waves in astrophysical plasma systems.« less

Molecular Handshake: Recognition through Weak Noncovalent Interactions

ERIC Educational Resources Information Center

Murthy, Parvathi S.

2006-01-01

The weak noncovalent interactions between substances, the handshake in the form of electrostatic interactions, van der Waals' interactions or hydrogen bonding is universal to all living and nonliving matter. They significantly influence the molecular and bulk properties and behavior of matter. Their transient nature affects chemical reactions and…

Surfactant-cobalt(III) complexes: The impact of hydrophobicity on interaction with HSA and DNA - insights from experimental and theoretical approach.

PubMed

Veeralakshmi, Selvakumar; Sabapathi, Gopal; Nehru, Selvan; Venuvanalingam, Ponnambalam; Arunachalam, Sankaralingam

2017-05-01

To develop surfactant-based metallodrugs, it is very important to know about their hydrophobicity, micelle forming capacity, their interaction with biomacromolecules such as proteins and nucleic acids, and biological activities. Here, diethylenetriamine (dien) and tetradecylamine ligand (TA) based surfactant-cobalt(III) complexes with single chain domain, [Co(dien)(TA)Cl 2 ]ClO 4 (1) and double chain domain [Co(dien)(TA) 2 Cl](ClO 4 ) 2 (2) were chosen to study the effect of hydrophobicity on the interaction with human serum albumin and calf thymus DNA. The obtained results showed that (i) single chain surfactant-cobalt(III) complex (1) interact with HSA and DNA via electrostatic interaction and groove binding, respectively; (ii) double chain surfactant-cobalt(III) complex (2) interact with HSA and DNA via hydrophobic interaction and partial intercalation, respectively, due to the play of hydrophobicity by single and double chain domains. Further it is noted that, double chain surfactant-cobalt(III) complex interact strongly with HSA and DNA, compared single chain surfactant-cobalt(III) complex due to their more hydrophobicity nature. DFT and molecular docking studies offer insights into the mechanism and mode of binding towards the molecular target CT-DNA and HSA. Hence, the present findings will create new avenue towards the use of hydrophobic metallodrugs for various therapeutic applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Substituent Effects in the Benzene Dimer are Due to Direct Interactions of the Substituents with the Unsubstituted Benzene

PubMed Central

Wheeler, Steven E.; Houk, K. N.

2009-01-01

The prevailing views of substituent effects in the sandwich configuration of the benzene dimer are flawed. For example, in the polar/π model of Cozzi and co-workers (J. Am. Chem. Soc. 1992, 114, 5729), electron-withdrawing substituents enhance binding in the benzene dimer by withdrawing electron density from the π-cloud of the substituted ring, reducing the repulsive electrostatic interaction with the non-substituted benzene. Conversely, electron-donating substituents donate excess electrons into the π-system and diminish the π-stacking interaction. We present computed interaction energies for the sandwich configuration of the benzene dimer and 24 substituted dimers, as well as sandwich complexes of substituted benzenes with perfluorobenzene. While the computed interaction energies correlate well with σm values for the substituents, interaction energies for related model systems demonstrate that this trend is independent of the substituted ring. Instead, the observed trends are consistent with direct electrostatic and dispersive interactions of the substituents with the unsubstituted ring. PMID:18652453

The electrostatic fluidic trap: a new approach to the spatial control and manipulation of matter at the nanometer scale (presentation video)

NASA Astrophysics Data System (ADS)

Krishnan, Madhavi

2014-09-01

I will describe a new technique to trap matter at the nanometer scale in fluids. Rather than apply external fields to the object of interest, our approach relies on spatial tailoring of the interaction between an object and its neighbouring surfaces in order to create spatial potential minima in three dimensions. We demonstrate how the strong and long-ranged electrostatic interaction can be modulated by tailoring substrate geometry to achieve stable spatial trapping of charged objects, as small as single proteins in solution.

Modified jeans instability for dust grains in a plasma.

PubMed

Delzanno, G L; Lapenta, G

2005-05-06

An investigation of the properties of linear stability is conducted for a system consisting of particles having mass m and charge q, interacting through the gravitational and electrostatic force (Jeans instability). However, in light of recent works showing that dust particles in a plasma can have a Lennard-Jones-like shielding potential, a new set of equations has been derived, where the electrostatic interaction among the dust particles is Lennard-Jones-like instead of Coulomb-like. A new condition for the gravitational instability is derived, showing a broader spectrum of unstable modes with faster growth rates.

Elucidation of amyloid beta-protein oligomerization mechanisms: discrete molecular dynamics study.

PubMed

Urbanc, B; Betnel, M; Cruz, L; Bitan, G; Teplow, D B

2010-03-31

Oligomers of amyloid beta-protein (Abeta) play a central role in the pathology of Alzheimer's disease. Of the two predominant Abeta alloforms, Abeta(1-40) and Abeta(1-42), Abeta(1-42) is more strongly implicated in the disease. We elucidated the structural characteristics of oligomers of Abeta(1-40) and Abeta(1-42) and their Arctic mutants, [E22G]Abeta(1-40) and [E22G]Abeta(1-42). We simulated oligomer formation using discrete molecular dynamics (DMD) with a four-bead protein model, backbone hydrogen bonding, and residue-specific interactions due to effective hydropathy and charge. For all four peptides under study, we derived the characteristic oligomer size distributions that were in agreement with prior experimental findings. Unlike Abeta(1-40), Abeta(1-42) had a high propensity to form paranuclei (pentameric or hexameric) structures that could self-associate into higher-order oligomers. Neither of the Arctic mutants formed higher-order oligomers, but [E22G]Abeta(1-40) formed paranuclei with a similar propensity to that of Abeta(1-42). Whereas the best agreement with the experimental data was obtained when the charged residues were modeled as solely hydrophilic, further assembly from spherical oligomers into elongated protofibrils was induced by nonzero electrostatic interactions among the charged residues. Structural analysis revealed that the C-terminal region played a dominant role in Abeta(1-42) oligomer formation whereas Abeta(1-40) oligomerization was primarily driven by intermolecular interactions among the central hydrophobic regions. The N-terminal region A2-F4 played a prominent role in Abeta(1-40) oligomerization but did not contribute to the oligomerization of Abeta(1-42) or the Arctic mutants. The oligomer structure of both Arctic peptides resembled Abeta(1-42) more than Abeta(1-40), consistent with their potentially more toxic nature.

A structure adapted multipole method for electrostatic interactions in protein dynamics

NASA Astrophysics Data System (ADS)

Niedermeier, Christoph; Tavan, Paul

1994-07-01

We present an algorithm for rapid approximate evaluation of electrostatic interactions in molecular dynamics simulations of proteins. Traditional algorithms require computational work of the order O(N2) for a system of N particles. Truncation methods which try to avoid that effort entail untolerably large errors in forces, energies and other observables. Hierarchical multipole expansion algorithms, which can account for the electrostatics to numerical accuracy, scale with O(N log N) or even with O(N) if they become augmented by a sophisticated scheme for summing up forces. To further reduce the computational effort we propose an algorithm that also uses a hierarchical multipole scheme but considers only the first two multipole moments (i.e., charges and dipoles). Our strategy is based on the consideration that numerical accuracy may not be necessary to reproduce protein dynamics with sufficient correctness. As opposed to previous methods, our scheme for hierarchical decomposition is adjusted to structural and dynamical features of the particular protein considered rather than chosen rigidly as a cubic grid. As compared to truncation methods we manage to reduce errors in the computation of electrostatic forces by a factor of 10 with only marginal additional effort.

Numerical Methods of Computational Electromagnetics for Complex Inhomogeneous Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai, Wei

Understanding electromagnetic phenomena is the key in many scientific investigation and engineering designs such as solar cell designs, studying biological ion channels for diseases, and creating clean fusion energies, among other things. The objectives of the project are to develop high order numerical methods to simulate evanescent electromagnetic waves occurring in plasmon solar cells and biological ion-channels, where local field enhancement within random media in the former and long range electrostatic interactions in the latter are of major challenges for accurate and efficient numerical computations. We have accomplished these objectives by developing high order numerical methods for solving Maxwell equationsmore » such as high order finite element basis for discontinuous Galerkin methods, well-conditioned Nedelec edge element method, divergence free finite element basis for MHD, and fast integral equation methods for layered media. These methods can be used to model the complex local field enhancement in plasmon solar cells. On the other hand, to treat long range electrostatic interaction in ion channels, we have developed image charge based method for a hybrid model in combining atomistic electrostatics and continuum Poisson-Boltzmann electrostatics. Such a hybrid model will speed up the molecular dynamics simulation of transport in biological ion-channels.« less

Electrostatic potentials of the S-locus F-box proteins contribute to the pollen S specificity in self-incompatibility in Petunia hybrida.

PubMed

Li, Junhui; Zhang, Yue; Song, Yanzhai; Zhang, Hui; Fan, Jiangbo; Li, Qun; Zhang, Dongfen; Xue, Yongbiao

2017-01-01

Self-incompatibility (SI) is a self/non-self discrimination system found widely in angiosperms and, in many species, is controlled by a single polymorphic S-locus. In the Solanaceae, Rosaceae and Plantaginaceae, the S-locus encodes a single S-RNase and a cluster of S-locus F-box (SLF) proteins to control the pistil and pollen expression of SI, respectively. Previous studies have shown that their cytosolic interactions determine their recognition specificity, but the physical force between their interactions remains unclear. In this study, we show that the electrostatic potentials of SLF contribute to the pollen S specificity through a physical mechanism of 'like charges repel and unlike charges attract' between SLFs and S-RNases in Petunia hybrida. Strikingly, the alteration of a single C-terminal amino acid of SLF reversed its surface electrostatic potentials and subsequently the pollen S specificity. Collectively, our results reveal that the electrostatic potentials act as a major physical force between cytosolic SLFs and S-RNases, providing a mechanistic insight into the self/non-self discrimination between cytosolic proteins in angiosperms. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Direct Force Measurements on Neurofilaments: Gel Expanded to Gel Condensed Transition

NASA Astrophysics Data System (ADS)

Beck, R.; Deek, J.; Jones, J. B.; Safinya, C. R.

2010-03-01

Neurofilaments (NFs)--the major cytoskeletal constituent of axons in vertebrates, consist of three subunit proteins assembled to form filaments with protruding unstructured C-terminus sidearms. Liquid crystal gel networks of sidearm-mediated NF assemblies play a key role in the mechanical while disruptions of this network, due to over-accumulation or incorrect sidearm interactions, are a hallmark of motor neuron diseases. Using synchrotron SAXS [1,2] and microscopy techniques [1,3] we report a direct force measurement of reconstituted NF-gels under osmotic pressure (P), which revealed the role of subunit sidearms on structure and interaction of NFs. With increasing P, near physiological condition, the gels undergo an abrupt nonreversible gel expanded to gel condensed transition that indicates sidearm-mediated attractions between NFs. This attraction is consistent with an electrostatic model of interpenetrating chains.[4pt] [1] J.B. Jones, C.R. Safinya, Biophys. J. 95, 823 (2008);[0pt] [2] R. Beck et al., Nature Mat. (2009) in press;[0pt] [3] H. Hess et al. Langmuir 24, 8397 (2008)

Dimensional control of supramolecular assemblies of diacetylene-derived peptide gemini amphiphile: from spherical micelles to foamlike networks.

PubMed

Jiang, Hao; Ehlers, Martin; Hu, Xiao-Yu; Zellermann, Elio; Schmuck, Carsten

2018-05-22

Peptide amphiphiles capable of assembling into multidimensional nanostructures have attracted much attention over the past decade due to their potential applications in materials science. Herein, a novel diacetylene-derived peptide gemini amphiphile with a fluorenylmethyloxycarbonyl (Fmoc) group at the N-terminus is reported to hierarchically assemble into spherical micelles, one-dimensional nanorods, two-dimensional foamlike networks and lamellae. Solvent polarity shows a remarkable effect on the self-assembled structures by changing the balance of four weak noncovalent interactions (hydrogen-bonding, π-π stacking, hydrophobic interaction, and electrostatic repulsion). We also show the time-evolution not only from spherical micelles to helical nanofibers in aqueous solution, but also from branched wormlike micelles to foamlike networks in methanol solution. In this work, the presence of the Fmoc group plays a key role in the self-assembly process. This work provides an efficient strategy for precise morphological control, aiding the future development in materials science.

Adsorption of Small Molecules at Water--Hexane and Water--Membrane Interfaces

NASA Astrophysics Data System (ADS)

Wilson, Michael A.

1996-03-01

The interaction of solutes with aqueous interfaces plays a significant role in a variety of physical processes, including general anesthesia and atmospheric chemistry. We present molecular dynamics results for the transfer of several small solutes across water liquid--vapor, water--hexane and water--GMO bilayer membrane interfaces. (A. Pohorille and M. A. Wilson, J. Chem. Phys. (in press, 1995).)^, (A. Pohorille, P. CIeplak, and M. A. Wilson, Chem. Phys. (in press, 1995).) The free energies of transferring small polar molecules across the interface exhibit fairly deep minima while those of nonpolar molecules do not. This is due to a balance between nonelectrostatic contributions --- primarily the work required to create a cavity large enough to accommodate the solute --- and the solute--solvent electrostatic interactions.^1 The surface excess of solute is calculated and compared with experimental results from the Gibbs adsorption isotherm. The interfacial solubilities correlate with measured anesthetic potencies of these compounds, implying that the binding sites for anesthetics are located near the water--membrane interface.

Automatic superposition of drug molecules based on their common receptor site

NASA Astrophysics Data System (ADS)

Kato, Yuichi; Inoue, Atsushi; Yamada, Miho; Tomioka, Nobuo; Itai, Akiko

1992-10-01

We have prevously developed a new rational method for superposing molecules in terms of submolecular physical and chemical properties, but not in terms of atom positions or chemical structures as has been done in the conventional methods. The program was originally developed for interactive use on a three-dimensional graphic display, providing goodness-of-fit indices on molecular shape, hydrogen bonds, electrostatic interactions and others. Here, we report a new unbiased searching method for the best superposition of molecules, covering all the superposing modes and conformational freedom, as an additional function of the program. The function is based on a novel least-squares method which superposes the expected positions and orientations of hydrogen bonding partners in the receptor that are deduced from both molecules. The method not only gives reliability and reproducibility to the result of the superposition, but also allows us to save labor and time. It is demonstrated that this method is very efficient for finding the correct superposing mode in such systems where hydrogen bonds play important roles.

Lysine succinylation of Mycobacterium tuberculosis isocitrate lyase (ICL) fine-tunes the microbial resistance to antibiotics.

PubMed

Zhou, Mingliang; Xie, Longxiang; Yang, Zhaozhen; Zhou, Jiahai; Xie, Jianping

2017-04-01

Lysine succinylation (Ksucc) is a newly identified protein posttranslational modification (PTM), which may play an important role in cellular physiology. However, the role of lysine succinylation in antibiotic resistance remains elusive. Isocitrate lyase (ICL) is crucial for broad-spectrum antibiotics tolerance in Mycobacterium tuberculosis (Mtb). We previously found that MtbICL (Rv0467) has at least three succinylated lysine residues, namely K189, K322, and K334.To explore the effect of succinylation on the activity of MtbICL, mutants' mimicry of the lysine succinylation were generated by site-directed mutagenesis. ICL-K189E mutant strain is more sensitive than the wild-type to rifampicin and streptomycin, but not isoniazid. For the in vitro activity of the purified isocitrate lyase, only K189E mutant showed significantly decreased activity. Crystal structure analysis showed that Lys189 Glu dramatically increased the pKa of Glu188 and decreased the pKa of Lys190, whereas had negligible effect on other residues within 5 Å as well as disruption of the electrostatic interaction between Lys189 and Glu182, which might prevent the closure of the active site loop and cause severe reduction of the enzyme activity. Considering the genetic, biochemical, and crystallographical evidences together, the succinylation of specific ICL residue can fine-tune the bacterial resistance to selected antibiotics. The decreased enzymatic activity resulting from the succinylation-changed electrostatic interaction might underlie this phenotype. This study provided the first insight into the link between lysine succinylation and antibiotic resistance.

pH-responsive ion transport in polyelectrolyte multilayers of poly(diallyldimethylammonium chloride) (PDADMAC) and poly(4-styrenesulfonic acid-co-maleic acid) (PSS-MA) bearing strong- and weak anionic groups.

PubMed

Maza, Eliana; Tuninetti, Jimena S; Politakos, Nikolaos; Knoll, Wolfgang; Moya, Sergio; Azzaroni, Omar

2015-11-28

The layer-by-layer construction of interfacial architectures displaying stimuli-responsive control of mass transport is attracting increasing interest in materials science. In this work, we describe the creation of interfacial architectures displaying pH-dependent ionic transport properties which until now have not been observed in polyelectrolyte multilayers. We describe a novel approach to create pH-controlled ion-rectifying systems employing polyelectrolyte multilayers assembled from a copolymer containing both weakly and strongly charged pendant groups, poly(4-styrenesulfonic acid-co-maleic acid) (PSS-MA), alternately deposited with poly(diallyldimethylammonium chloride) (PDADMAC). The conceptual framework is based on the very contrasting and differential interactions of PSS and MA units with PDADMAC. In our setting, sulfonate groups play a structural role by conferring stability to the multilayer due to the strong electrostatic interactions with the polycations, while the weakly interacting MA groups remain "silent" within the film and then act as on-demand pH-responsive units. When these multilayers are combined with a strong cationic capping layer that repels the passage of cationic probes, a pH-gateable rectified transport of anions is observed. Concomitantly, we also observed that these functional properties are significantly affected when multilayers are subjected to extensive pH cycling as a consequence of irreversible morphological changes taking place in the film. We envision that the synergy derived from combining weak and strong interactions within the same multilayer will play a key role in the construction of new interfacial architectures displaying tailorable ion transport properties.

The effect of charge mutations on the stability and aggregation of a human single chain Fv fragment.

PubMed

Austerberry, James I; Dajani, Rana; Panova, Stanislava; Roberts, Dorota; Golovanov, Alexander P; Pluen, Alain; van der Walle, Christopher F; Uddin, Shahid; Warwicker, Jim; Derrick, Jeremy P; Curtis, Robin

2017-06-01

The aggregation propensities for a series of single-chain variable fragment (scFv) mutant proteins containing supercharged sequences, salt bridges and lysine/arginine-enriched motifs were characterised as a function of pH and ionic strength to isolate the electrostatic contributions. Recent improvements in aggregation predictors rely on using knowledge of native-state protein-protein interactions. Consistent with previous findings, electrostatic contributions to native protein-protein interactions correlate with aggregate growth pathway and rates. However, strong reversible self-association observed for selected mutants under native conditions did not correlate with aggregate growth, indicating 'sticky' surfaces that are exposed in the native monomeric state are inaccessible when aggregates grow. We find that even though similar native-state protein-protein interactions occur for the arginine and lysine-enriched mutants, aggregation propensity is increased for the former and decreased for the latter, providing evidence that lysine suppresses interactions between partially folded states under these conditions. The supercharged mutants follow the behaviour observed for basic proteins under acidic conditions; where excess net charge decreases conformational stability and increases nucleation rates, but conversely reduces aggregate growth rates due to increased intermolecular electrostatic repulsion. The results highlight the limitations of using conformational stability and native-state protein-protein interactions as predictors for aggregation propensity and provide guidance on how to engineer stabilizing charged mutations. Copyright © 2017. Published by Elsevier B.V.

Parallel tempering Monte Carlo simulations of lysozyme orientation on charged surfaces

NASA Astrophysics Data System (ADS)

Xie, Yun; Zhou, Jian; Jiang, Shaoyi

2010-02-01

In this work, the parallel tempering Monte Carlo (PTMC) algorithm is applied to accurately and efficiently identify the global-minimum-energy orientation of a protein adsorbed on a surface in a single simulation. When applying the PTMC method to simulate lysozyme orientation on charged surfaces, it is found that lysozyme could easily be adsorbed on negatively charged surfaces with "side-on" and "back-on" orientations. When driven by dominant electrostatic interactions, lysozyme tends to be adsorbed on negatively charged surfaces with the side-on orientation for which the active site of lysozyme faces sideways. The side-on orientation agrees well with the experimental results where the adsorbed orientation of lysozyme is determined by electrostatic interactions. As the contribution from van der Waals interactions gradually dominates, the back-on orientation becomes the preferred one. For this orientation, the active site of lysozyme faces outward, which conforms to the experimental results where the orientation of adsorbed lysozyme is co-determined by electrostatic interactions and van der Waals interactions. It is also found that despite of its net positive charge, lysozyme could be adsorbed on positively charged surfaces with both "end-on" and back-on orientations owing to the nonuniform charge distribution over lysozyme surface and the screening effect from ions in solution. The PTMC simulation method provides a way to determine the preferred orientation of proteins on surfaces for biosensor and biomaterial applications.

Tuning of electrostatic vs. depletion interaction in deciding the phase behavior of nanoparticle-polymer system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Sugam, E-mail: sugam@barc.gov.in; Aswal, V. K.; Kohlbrecher, J.

2015-06-24

Nanoparticle-polymer system interestingly show a re-entrant phase behavior where charge stabilized silica nanoparticles (phase I) undergo particle clustering (phase II) and then back to individual particles (phase I) as a function of polymer concentration. Such phase behavior arises as a result of dominance of various interactions (i) nanoparticle-nanoparticle electrostatic repulsion (ii) polymer induced attractive depletion between nanoparticles and (iii) polymer-polymer repulsion, at different concentration regimes. Small-angle neutron scattering (SANS) has been used to study the evolution of interaction during this re-entrant phase behavior of nanoparticles by contrast-marching the polymer. The SANS data have been modeled using a two-Yukawa potential accountingmore » for both attractive and repulsive parts of the interaction between nanoparticles. The degree of both of these parts has been separately tuned by varying the polymer concentration and ionic strength of the solution. Both of these parts are found to have long-range nature. At low polymer concentrations, the electrostatic repulsion dominates over the depletion attraction. The magnitude and the range of the depletion interaction increase with the polymer concentration leading to nanoparticle clustering. At higher polymer concentrations, the increased polymer-polymer repulsion reduces the strength of depletion leading to re-entrant phase behavior. The clusters formed under depletion attraction are found to have surface fractal morphology.« less