Science.gov

Sample records for investigating molecular interactions

  1. A Molecular Investigation of Genotype by Environment Interactions

    PubMed Central

    Dean, A. M.

    1995-01-01

    The fitnesses conferred by seven lactose operons, which had been transduced into a common genetic background from natural isolates of Escherichia coli, were determined during competition for growth rate-limiting quantities of galactosyl-glycerol, a naturally occurring galactoside. The fitnesses of these same operons have been previously determined on lactose and three artificial galactosides, lactulose, methyl-galactoside and galactosyl-arabinose. Analysis suggests that although marked genotype by environment interactions occur, changes in the fitness rankings are rare. The relative activities of the β-galactosidases and the permeases were determined on galactosyl-glycerol, lactose, lactulose and methyl-galactoside. Both enzymes display considerable kinetic variation. The β-galactosidase alleles provide no evidence for genotype by environment interactions at the level of enzyme activity. The permease alleles display genotype by environment interactions with a few causing changes in activity rankings. The contributions to fitness made by the permeases and the β-galactosidases were partitioned using metabolic control analysis. Most of the genotype by environment interaction at the level of fitness is generated by changes in the distribution of control among steps in the pathway, particularly at the permease where large control coefficients ensure that its kinetic variation has marked fitness effects. Indeed, changes in activity rankings at the permease account for the few changes in fitness rankings. In contrast, the control coefficients of the β-galactosidase are sufficiently small that its kinetic variation is in, or close to, the neutral limit. The selection coefficients are larger on the artificial galactosides because the control coefficients of the permease and β-galactosidase are larger. The flux summation theorem requires that control coefficients associated with other steps in the pathway must be reduced, implying that the selection at these steps will

  2. Spectroscopic investigations, molecular interactions, and molecular docking studies on the potential inhibitor "thiophene-2-carboxylicacid".

    PubMed

    Karthick, T; Balachandran, V; Perumal, S

    2015-04-15

    Thiophene derivatives have been focused in the past decades due to their remarkable biological and pharmacological activities. In connection with that the conformational stability, spectroscopic characterization, molecular (inter- and intra-) interactions, and molecular docking studies on thiophene-2-carboxylicacid have been performed in this work by experimental FT-IR and theoretical quantum chemical computations. Experimentally recorded FT-IR spectrum in the region 4000-400 cm(-1) has been compared with the scaled theoretical spectrum and the spectral peaks have been assigned on the basis of potential energy distribution results obtained from MOLVIB program package. The conformational stability of monomer and dimer conformers has been examined. The presence of inter- and intramolecular interactions in the monomer and dimer conformers have been explained by natural bond orbital analysis. The UV-Vis spectra of the sample in different solvents have been simulated and solvent effects were predicted by polarisable continuum model with TD-DFT/B3LYP/6-31+G(d,p) method. To test the biological activity of the sample, molecular docking (ligand-protein) simulations have been performed using SWISSDOCK web server. The full fitness (FF) score and binding affinity values revealed that thiophene-2-carboxylicacid can act as potential inhibitor against inflammation.

  3. Spectroscopic investigations, molecular interactions, and molecular docking studies on the potential inhibitor "thiophene-2-carboxylicacid"

    NASA Astrophysics Data System (ADS)

    Karthick, T.; Balachandran, V.; Perumal, S.

    2015-04-01

    Thiophene derivatives have been focused in the past decades due to their remarkable biological and pharmacological activities. In connection with that the conformational stability, spectroscopic characterization, molecular (inter- and intra-) interactions, and molecular docking studies on thiophene-2-carboxylicacid have been performed in this work by experimental FT-IR and theoretical quantum chemical computations. Experimentally recorded FT-IR spectrum in the region 4000-400 cm-1 has been compared with the scaled theoretical spectrum and the spectral peaks have been assigned on the basis of potential energy distribution results obtained from MOLVIB program package. The conformational stability of monomer and dimer conformers has been examined. The presence of inter- and intramolecular interactions in the monomer and dimer conformers have been explained by natural bond orbital analysis. The UV-Vis spectra of the sample in different solvents have been simulated and solvent effects were predicted by polarisable continuum model with TD-DFT/B3LYP/6-31+G(d,p) method. To test the biological activity of the sample, molecular docking (ligand-protein) simulations have been performed using SWISSDOCK web server. The full fitness (FF) score and binding affinity values revealed that thiophene-2-carboxylicacid can act as potential inhibitor against inflammation.

  4. An investigation of molecular dynamics simulation and molecular docking: interaction of citrus flavonoids and bovine β-lactoglobulin in focus.

    PubMed

    Sahihi, M; Ghayeb, Y

    2014-08-01

    Citrus flavonoids are natural compounds with important health benefits. The study of their interaction with a transport protein, such as bovine β-lactoglobulin (BLG), at the atomic level could be a valuable factor to control their transport to biological sites. In the present study, molecular docking and molecular dynamics simulation methods were used to investigate the interaction of hesperetin, naringenin, nobiletin and tangeretin as citrus flavonoids and BLG as transport protein. The molecular docking results revealed that these flavonoids bind in the internal cavity of BLG and the BLG affinity for binding the flavonoids follows naringenin>hesperetin>tangeretin>nobiletin. The docking results also indicated that the BLG-flavonoid complexes are stabilized through hydrophobic interactions, hydrogen bond interactions and π-π stacking interactions. The analysis of molecular dynamics (MD) simulation trajectories showed that the root mean square deviation (RMSD) of various systems reaches equilibrium and fluctuates around the mean value at various times. Time evolution of the radius of gyration, total solvent accessible surface of the protein and the second structure of protein showed as well that BLG and BLG-flavonoid complexes were stable around 2500ps, and there was not any conformational change as for BLG-flavonoid complexes. Further, the profiles of atomic fluctuations indicated the rigidity of the ligand binding site during the simulation.

  5. Interaction of sulfanilamide and sulfamethoxazole with bovine serum albumin and adenine: spectroscopic and molecular docking investigations.

    PubMed

    Rajendiran, N; Thulasidhasan, J

    2015-06-01

    Interaction between sulfanilamide (SAM) and sulfamethoxazole (SMO) with BSA and DNA base (adenine) was investigated by UV-visible, fluorescence, cyclic voltammetry and molecular docking studies. Stern-Volmer fluorescence quenching constant (Ka) suggests SMO is more quenched with BSA/adenine than that of SAM. The distance r between donor (BSA/adenine) and acceptor (SAM and SMO) was obtained according to fluorescence resonance energy transfer (FRET). The results showed that hydrophobic forces, electrostatic interactions, and hydrogen bonds played vital roles in the SAM and SMO with BSA/adenine binding interaction. During the interaction, sulfa drugs could insert into the hydrophobic pocket, where the non-radioactive energy transfer from BSA/adenine to sulfa drugs occurred with high possibility. Cyclic voltammetry results suggested that when the drug concentration is increased, the anodic electrode potential deceased. The docking method indicates aniline group is interacted with the BSA molecules. PMID:25754395

  6. Interaction of sulfanilamide and sulfamethoxazole with bovine serum albumin and adenine: Spectroscopic and molecular docking investigations

    NASA Astrophysics Data System (ADS)

    Rajendiran, N.; Thulasidhasan, J.

    2015-06-01

    Interaction between sulfanilamide (SAM) and sulfamethoxazole (SMO) with BSA and DNA base (adenine) was investigated by UV-visible, fluorescence, cyclic voltammetry and molecular docking studies. Stern-Volmer fluorescence quenching constant (Ka) suggests SMO is more quenched with BSA/adenine than that of SAM. The distance r between donor (BSA/adenine) and acceptor (SAM and SMO) was obtained according to fluorescence resonance energy transfer (FRET). The results showed that hydrophobic forces, electrostatic interactions, and hydrogen bonds played vital roles in the SAM and SMO with BSA/adenine binding interaction. During the interaction, sulfa drugs could insert into the hydrophobic pocket, where the non-radioactive energy transfer from BSA/adenine to sulfa drugs occurred with high possibility. Cyclic voltammetry results suggested that when the drug concentration is increased, the anodic electrode potential deceased. The docking method indicates aniline group is interacted with the BSA molecules.

  7. Investigation into the molecular and thermodynamic basis of protein interactions in multimodal chromatography using functionalized nanoparticles.

    PubMed

    Srinivasan, Kartik; Parimal, Siddharth; Lopez, Maria M; McCallum, Scott A; Cramer, Steven M

    2014-11-11

    Although multimodal chromatography offers significant potential for bioseparations, there is a lack of molecular level understanding of the nature of protein binding in these systems. In this study a nanoparticle system is employed that can simulate a chromatographic resin surface while also being amenable to isothermal titration calorimetry (ITC) and solution NMR. ITC and NMR titration experiments are carried out with (15)N-labeled ubiquitin to investigate the interactions of ubiquitin with nanoparticles functionalized with two industrially important multimodal ligands. The ITC results suggest that binding to both multimodal ligand surfaces is entropically driven over a range of temperatures and that this is due primarily to the release of surface bound waters. In order to reveal structural details of the interaction process, binding-induced chemical shift changes obtained from the NMR experiments are employed to obtain dissociation constants of individual amino acid residues on the protein surface. The residue level information obtained from NMR is then used to identify a preferred binding face on ubiquitin for interaction to both multimodal ligand surfaces. In addition, electrostatic potential and spatial aggregation propensity maps are used to determine important protein surface property data that are shown to correlate well with the molecular level information obtained from NMR. Importantly, the data demonstrate that the cluster of interacting residues on the protein surface act co-operatively to give rise to multimodal binding affinities several orders of magnitude greater than those obtained previously for interactions with free solution ligands. The use of NMR and ITC to study protein interactions with functionalized nanoparticles offers a new tool for obtaining important molecular and thermodynamic insights into protein affinity in multimodal chromatographic systems. PMID:25310519

  8. Investigation of molecular interaction between cefpodoxime acid and human mixtard insulin by ultrasonic and spectral methods.

    PubMed

    Ganesh, T; Kannappan, V; Mohamed Kamil, M G; Kumar, R

    2016-09-10

    This paper deals with the extensive investigation of molecular interaction between third generation cephalosporin antibiotic, Cefpodoxime Acid (CA) and Human Mixtard Insulin (HMI) in an aqueous medium through ultrasonic, dilute solution viscometric (DSV) and spectral [UV-vis, Attenuated total reflection (ATR)-FT IR] methods at various blend compositions of the drug and insulin at three different (303K, 310K and 313K) temperatures. This is an attempt to unravel the possibility of drug induced hypoglycemic effect. The existence of solute-solute interaction in aqueous solutions of CA and HMI is established from the variation of ultrasonic velocity and other acoustical parameters with blend composition. DSV method is used to confirm the range of blend composition at which the molecular interaction is significant. The conclusions drawn from ultrasonic and DSV methods are further established by the UV-vis and ATR- FT IR spectral studies of ternary mixtures at different blend compositions. Further, the existing interactions suggest the possibility of cefpodoxime acid induced hypoglycemia which is discussed based on the structural aspects of the two components.

  9. Investigation of the Interaction of Naringin Palmitate with Bovine Serum Albumin: Spectroscopic Analysis and Molecular Docking

    PubMed Central

    Zhang, Xia; Li, Lin; Xu, Zhenbo; Liang, Zhili; Su, Jianyu; Huang, Jianrong; Li, Bing

    2013-01-01

    Background Bovine serum albumin (BSA) contains high affinity binding sites for several endogenous and exogenous compounds and has been used to replace human serum albumin (HSA), as these two compounds share a similar structure. Naringin palmitate is a modified product of naringin that is produced by an acylation reaction with palmitic acid, which is considered to be an effective substance for enhancing naringin lipophilicity. In this study, the interaction of naringin palmitate with BSA was characterised by spectroscopic and molecular docking techniques. Methodology/Principal Findings The goal of this study was to investigate the interactions between naringin palmitate and BSA under physiological conditions, and differences in naringin and naringin palmitate affinities for BSA were further compared and analysed. The formation of naringin palmitate-BSA was revealed by fluorescence quenching, and the Stern-Volmer quenching constant (KSV) was found to decrease with increasing temperature, suggesting that a static quenching mechanism was involved. The changes in enthalpy (ΔH) and entropy (ΔS) for the interaction were detected at −4.11±0.18 kJ·mol−1 and −76.59±0.32 J·mol−1·K−1, respectively, which indicated that the naringin palmitate-BSA interaction occurred mainly through van der Waals forces and hydrogen bond formation. The negative free energy change (ΔG) values of naringin palmitate at different temperatures suggested a spontaneous interaction. Circular dichroism studies revealed that the α-helical content of BSA decreased after interacting with naringin palmitate. Displacement studies suggested that naringin palmitate was partially bound to site I (subdomain IIA) of the BSA, which was also substantiated by the molecular docking studies. Conclusions/Significance In conclusion, naringin palmitate was transported by BSA and was easily removed afterwards. As a consequence, an extension of naringin applications for use in food, cosmetic and medicinal

  10. Molecular dynamics investigation of the interaction of dislocations with carbides in BCC Fe

    NASA Astrophysics Data System (ADS)

    Granberg, F.; Terentyev, D.; Nordlund, K.

    2015-06-01

    Different types of carbides are present in many steels used as structural materials. To safely use steel in demanding environments, like nuclear power plants, it is important to know how defects will affect the mechanical properties of the material. In this study, the effect of carbide precipitates on the edge dislocation movement is investigated. Three different types of carbides were investigated by means of molecular dynamics, with a Tersoff-like bond order interatomic potential by Henriksson et al. The obstacles were 4 nm in diameter and were of Fe3C- (cementite-), Fe23C6- and Cr23C6-type. The critical unpinning stress was calculated for each type at different temperatures, to get the temperature-dependent obstacle strength. The results showed a decreasing critical stress with increasing temperature, consistent with previous studies. The critical unpinning stress was seen to be dependent on the type of carbide, but the differences were small. A difference was also observed between the obstacles with the same structure, but with different composition. This study shows the relation between the existing Cr23C6 carbide and the experimentally non-existing Fe23C6 carbide, which needs to be used as a model system for investigations with interatomic potentials not able to describe the interaction of Cr in the Fe-C-system. We found the difference to be a between 7% and 10% higher critical unpinning stress for the chromium carbide, than for the iron carbide of the same type.

  11. Investigations of drug-DNA interactions using molecular docking, cyclic voltammetry and UV-Vis spectroscopy

    NASA Astrophysics Data System (ADS)

    Perveen, Fouzia; Qureshi, Rumana; Ansari, Farzana Latif; Kalsoom, Saima; Ahmed, Safeer

    2011-10-01

    Molecular docking and QSAR studies were carried out for the investigation of interactions between 11 antitumor drugs and double stranded DNA. Quantitative structure activity relationship was established using MOE software package showing good correlation of binding strength with various physicochemical parameters e.g., hydrophobic surface area ( Vsurf), EHOMO, EHUMO, partition coefficient (log P) and molar refractivity ( M R) of the drugs . The most important parameter obtained from the docking studies was the formation constant ( K f) which is an indicative of the binding strength of the drug with DNA. This parameter was also calculated using the experimental techniques namely cyclic voltammetry (CV) and UV-Vis spectrophotometry. Variation in electrochemical characteristics (shift in peak potential and peak current decrease) and spectral profile of these drugs on the addition of DNA were used to determine the values of formation constant. The docking studies were used to predict the mode of interaction of the drug with DNA. It was observed that as far as binding strength was concerned the computational results complemented the experimental results. The order of magnitude of experimental and theoretical K f was same. The high value of K f implied that the respective drugs bind to DNA most efficiently.

  12. Investigating molecular interactions between beta-lactoglobulin and sugar beet pectin by multi-detection HPSEC

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Molecular interaction between beta-lactoglobulin (beta-LG) and beta-sugar beet pectin (beta-SBP), both by direct mixing and by thermal treatment prior to mixing at pH 6.75 and low ionic strength (50 mM) was studied using High Performance Size Exclusion Chromatography (HPSEC). The analysis of the hy...

  13. Computational and experimental investigation of DNA repair protein photolyase interactions with low molecular weight drugs.

    PubMed

    Azizoğlu, Selimcan; Kizilel, Riza; Marušič, Maja; Kavakli, Ibrahim Halil; Erman, Burak; Kizilel, Seda

    2013-07-01

    This paper reports the previously unknown interactions between eight low molecular weight commercially available drugs (130-800 Da) and DNA repair protein photolyase using computational docking simulations and surface plasmon resonance (SPR) experiments. Theoretical dissociation constants, K(d), obtained from molecular docking simulations were compared with the values found from SPR experiments. Among the eight drugs analyzed, computational and experimental values showed similar binding affinities between selected drug and protein pairs. We found no significant differences in binding interactions between pure and commercial forms of the drug lornoxicam and DNA photolyase. Among the eight drugs studied, prednisone, desloratadine, and azelastine exhibited the highest binding affinity (K(d) = 1.65, 2.05, and 8.47 μM, respectively) toward DNA photolyase. Results obtained in this study are promising for use in the prediction of unknown interactions of common drugs with specific proteins such as human clock protein cryptochrome. PMID:23657985

  14. Structure based investigation on the binding interaction of transport proteins in leishmaniasis: insights from molecular simulation.

    PubMed

    Singh, Shailza; Mandlik, Vineetha

    2015-05-01

    Leishmania major is the causative agent of cutaneous leishmaniasis which affects over 1 million people in 88 different countries. The incidence of this disease is on the rise due to the current problems associated with the present chemotherapeutics. In addition, Leishmania confronts resistance to the traditional drugs like sodium stibogluconate and newer repurposed drugs like miltefosine. ABC transporters are involved in the development of drug resistance. Miltefosine, the drug used for the treatment of leishmaniasis, is effluxed by P4 ATPase and ABC transporter, which is the prime focus of our study in this paper. P4 ATPase (MDR1) along with an unnamed protein (cdc50) translocates miltefosine from the outer to the inner leaflet by the process of flipping which is ATP driven. In contrast, miltefosine also escapes from the cells by an energy dependent mechanism that involves the ABC transporter protein (ABC). It is known that certain genes in the parasite amplify the portions of a gene which encodes ABC transporter and P4 ATPase involved in translocating phospholipids and hence resistance to miltefosine. We observed the ABC and P4 ATPase genes, 39 T-box elements were observed in the ABC transporter protein and three elements were observed in the P4 ATPase gene suggesting its role in transcription regulation. To the best of our knowledge, there are no structural and regulatory reports on these two proteins in L. major. Computational structural biology tools may aid in understanding the interaction of miltefosine with the P4-ATPase-cdc50 complex and the ABC transporter. This can be achieved by modeling the target protein structures, studying the dynamics associated with the different domains of the protein and later using activators and inhibitors to alter the functioning of the protein. Molecular dynamics simulation with a lipid bilayer is performed to investigate the conformational changes and structure-activity relationship. As transporters are difficult to model

  15. Molecular Modeling of Myrosinase from Brassica oleracea: A Structural Investigation of Sinigrin Interaction

    PubMed Central

    Natarajan, Sathishkumar; Thamilarasan, Senthil Kumar; Park, Jong-In; Chung, Mi-Young; Nou, Ill-Sup

    2015-01-01

    Myrosinase, which is present in cruciferous plant species, plays an important role in the hydrolysis of glycosides such as glucosinolates and is involved in plant defense. Brassicaceae myrosinases are diverse although they share common ancestry, and structural knowledge about myrosinases from cabbage (Brassica oleracea) was needed. To address this, we constructed a three-dimensional model structure of myrosinase based on Sinapis alba structures using Iterative Threading ASSEmbly Refinement server (I-TASSER) webserver, and refined model coordinates were evaluated with ProQ and Verify3D. The resulting model was predicted with β/α fold, ten conserved N-glycosylation sites, and three disulfide bridges. In addition, this model shared features with the known Sinapis alba myrosinase structure. To obtain a better understanding of myrosinase–sinigrin interaction, the refined model was docked using Autodock Vina with crucial key amino acids. The key nucleophile residues GLN207 and GLU427 were found to interact with sinigrin to form a hydrogen bond. Further, 20-ns molecular dynamics simulation was performed to examine myrosinase–sinigrin complex stability, revealing that residue GLU207 maintained its hydrogen bond stability throughout the entire simulation and structural orientation was similar to that of the docked state. This conceptual model should be useful for understanding the structural features of myrosinase and their binding orientation with sinigrin. PMID:26703735

  16. Using the fragment molecular orbital method to investigate agonist-orexin-2 receptor interactions.

    PubMed

    Heifetz, Alexander; Aldeghi, Matteo; Chudyk, Ewa I; Fedorov, Dmitri G; Bodkin, Mike J; Biggin, Philip C

    2016-04-15

    The understanding of binding interactions between any protein and a small molecule plays a key role in the rationalization of affinity and selectivity and is essential for an efficient structure-based drug discovery (SBDD) process. Clearly, to begin SBDD, a structure is needed, and although there has been fantastic progress in solving G-protein-coupled receptor (GPCR) crystal structures, the process remains quite slow and is not currently feasible for every GPCR or GPCR-ligand complex. This situation significantly limits the ability of X-ray crystallography to impact the drug discovery process for GPCR targets in 'real-time' and hence there is still a need for other practical and cost-efficient alternatives. We present here an approach that integrates our previously described hierarchical GPCR modelling protocol (HGMP) and the fragment molecular orbital (FMO) quantum mechanics (QM) method to explore the interactions and selectivity of the human orexin-2 receptor (OX2R) and its recently discovered nonpeptidic agonists. HGMP generates a 3D model of GPCR structures and its complexes with small molecules by applying a set of computational methods. FMO allowsab initioapproaches to be applied to systems that conventional QM methods would find challenging. The key advantage of FMO is that it can reveal information on the individual contribution and chemical nature of each residue and water molecule to the ligand binding that normally would be difficult to detect without QM. We illustrate how the combination of both techniques provides a practical and efficient approach that can be used to analyse the existing structure-function relationships (SAR) and to drive forward SBDD in a real-world example for which there is no crystal structure of the complex available.

  17. Investigation the interaction of Daphnin with human serum albumin using optical spectroscopy and molecular modeling methods

    NASA Astrophysics Data System (ADS)

    Zhu, Jinhua; Wu, Liye; Zhang, Qingyou; Chen, Xingguo; Liu, Xiuhua

    2012-09-01

    The interaction between Daphnin with human serum albumin has been studied for the first time by spectroscopic methods including fluorescence quenching technology, circular dichroism (CD) spectroscopy and Fourier transform infrared (FT-IR) spectroscopy under simulative physiological conditions. The results of fluorescence titration revealed that Daphnin can quench the intrinsic fluorescence of HSA by static quenching and there is a single class of binding site on HSA. In addition, the studies of CD spectroscopy and FT-IR spectroscopy showed that the protein secondary structure changed with increases of α-helices at the drug to protein molar ratio of 2. Furthermore, the thermodynamic functions ΔH0 and ΔS0 for the reaction were calculated to be 11.626 kJ mol-1 and 118.843 J mol-1 K-1 according to Van't Hoff equation. The thermodynamic parameters (ΔH0 and ΔS0) and the molecular modeling study indicated that hydrophobic force played an important role to stabilize the Daphnin-HSA complex, and Daphnin could bind within the subdomain IIA of the HSA.

  18. MDM2-MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance.

    PubMed

    Moscetti, Ilaria; Teveroni, Emanuela; Moretti, Fabiola; Bizzarri, Anna Rita; Cannistraro, Salvatore

    2016-01-01

    Murine double minute 2 (MDM2) and 4 (MDM4) are known as the main negative regulators of p53, a tumor suppressor. They are able to form heterodimers that are much more effective in the downregulation of p53. Therefore, the MDM2-MDM4 complex could be a target for promising therapeutic restoration of p53 function. To this aim, a deeper understanding of the molecular mechanisms underlining the heterodimerization is needed. The kinetic and thermodynamic characterization of the MDM2-MDM4 complex was performed with two complementary approaches: atomic force spectroscopy and surface plasmon resonance. Both techniques revealed an equilibrium dissociation constant (KD ) in the micromolar range for the MDM2-MDM4 heterodimer, similar to related complexes involved in the p53 network. Furthermore, the MDM2-MDM4 complex is characterized by a relatively high free energy, through a single energy barrier, and by a lifetime in the order of tens of seconds. New insights into the MDM2-MDM4 interaction could be highly important for developing innovative anticancer drugs focused on p53 reactivation. PMID:27621617

  19. Investigating molecular interactions and surface morphology of wax-doped asphaltenes.

    PubMed

    Pahlavan, Farideh; Mousavi, Masoumeh; Hung, Albert; Fini, Ellie H

    2016-04-01

    The nature and origin of bee-like microstructures (bees) in asphalt binders and their impact on asphalt oxidation have been the subject of extensive discussions in recent years. While several studies refer to the bees as solely surface features, some others consider them to be bulk microcrystalline components that are formed due to co-precipitation of wax and asphaltene molecules. In this study, we use a rigorous theoretical and experimental approach to investigate the interplay of asphalt components (mainly asphaltene and wax) and their impact on bee formation. In the theoretical section, quantum-mechanical calculations using density functional theory (DFT) are used to evaluate the strength of interactions between asphaltene unit sheets in the presence and absence of a wax component, as well as the mutual interactions between asphaltene molecules (monomers and dimers) and paraffin wax. The results of this section reveal that paraffin waxes not only do not reinforce the interaction between the asphaltene unit sheets, they destabilize asphaltene assembly and dimerization. AIM (Atom in Molecules) analysis shows the destabilizing effect of wax on asphaltene assembly as a reduction in the number of cage and bond critical points between asphaltenes. This destabilization effect among interacting systems (asphaltene-asphaltene and wax-asphaltene) does not support the hypothesis that interaction between paraffin waxes and non-wax components, such as asphaltene, is responsible for their co-precipitation and bee formation. To further examine the effect of wax component on asphalt microstructure experimentally, we used atomic force microscopy (AFM) to study the surface morphology of an asphalt sample doped with 1% to 25% paraffin wax. In agreement with the conclusions drawn from the DFT approach, our experiments indicate that paraffin wax tends to crystallize separately and form lamellar paraffin wax crystal inclusions with 10 nm thickness. Moreover, the addition of 3% wax

  20. Investigating molecular interactions and surface morphology of wax-doped asphaltenes.

    PubMed

    Pahlavan, Farideh; Mousavi, Masoumeh; Hung, Albert; Fini, Ellie H

    2016-04-01

    The nature and origin of bee-like microstructures (bees) in asphalt binders and their impact on asphalt oxidation have been the subject of extensive discussions in recent years. While several studies refer to the bees as solely surface features, some others consider them to be bulk microcrystalline components that are formed due to co-precipitation of wax and asphaltene molecules. In this study, we use a rigorous theoretical and experimental approach to investigate the interplay of asphalt components (mainly asphaltene and wax) and their impact on bee formation. In the theoretical section, quantum-mechanical calculations using density functional theory (DFT) are used to evaluate the strength of interactions between asphaltene unit sheets in the presence and absence of a wax component, as well as the mutual interactions between asphaltene molecules (monomers and dimers) and paraffin wax. The results of this section reveal that paraffin waxes not only do not reinforce the interaction between the asphaltene unit sheets, they destabilize asphaltene assembly and dimerization. AIM (Atom in Molecules) analysis shows the destabilizing effect of wax on asphaltene assembly as a reduction in the number of cage and bond critical points between asphaltenes. This destabilization effect among interacting systems (asphaltene-asphaltene and wax-asphaltene) does not support the hypothesis that interaction between paraffin waxes and non-wax components, such as asphaltene, is responsible for their co-precipitation and bee formation. To further examine the effect of wax component on asphalt microstructure experimentally, we used atomic force microscopy (AFM) to study the surface morphology of an asphalt sample doped with 1% to 25% paraffin wax. In agreement with the conclusions drawn from the DFT approach, our experiments indicate that paraffin wax tends to crystallize separately and form lamellar paraffin wax crystal inclusions with 10 nm thickness. Moreover, the addition of 3% wax

  1. Investigating the Interaction of Fe Nanoparticles with Lysozyme by Biophysical and Molecular Docking Studies

    PubMed Central

    Aghili, Zahra; Taheri, Saba; Zeinabad, Hojjat Alizadeh; Pishkar, Leila; Saboury, Ali Akbar; Rahimi, Arash; Falahati, Mojtaba

    2016-01-01

    Herein, the interaction of hen egg white lysozyme (HEWL) with iron nanoparticle (Fe NP) was investigated by spectroscopic and docking studies. The zeta potential analysis revealed that addition of Fe NP (6.45±1.03 mV) to HEWL (8.57±0.54 mV) can cause to greater charge distribution of nanoparticle-protein system (17.33±1.84 mV). In addition, dynamic light scattering (DLS) study revealed that addition of Fe NP (92.95±6.11 nm) to HEWL (2.68±0.37 nm) increases suspension potential of protein/nanoparticle system (51.17±3.19 nm). Fluorescence quenching studies reveled that both static and dynamic quenching mechanism occur and hydrogen bond and van der Waals interaction give rise to protein-NP system. Synchronous fluorescence spectroscopy of HEWL in the presence of Fe NP showed that the emission maximum wavelength of tryptophan (Trp) residues undergoes a red-shift. ANS fluorescence data indicated a dramatic exposure of hydrophobic residues to the solvent. The considerable reduction in melting temperature (T(m)) of HEWL after addition of Fe NP determines an unfavorable interaction system. Furthermore circular dichoroism (CD) experiments demonstrated that, the secondary structure of HEWL has not changed with increasing Fe NP concentrations; however, some conformational changes occur in tertiary structure of HEWL. Moreover, protein–ligand docking study confirmed that the Fe NP forms hydrogen bond contacts with HEWL. PMID:27776180

  2. Spectroscopic investigations on the interaction between carbon nanotubes and catalase on molecular level.

    PubMed

    Guan, Jin; Dai, Jingping; Zhao, Xingchen; Liu, Chunhua; Gao, Canzhu; Liu, Rutao

    2014-05-01

    The interactions between well-dispersed multiwalled carbon nanotubes (MWCNTs) and catalase (CAT) were investigated. The activity of CAT was inhibited with the addition of MWCNTs. After deducting the inner filter effect, the fluorescence spectra revealed that the tryptophan (Trp) residues were exposed and the fluorescence intensities of CAT increased with the increase in the MWCNTs concentration. At the same time, the environment of the Trp residues became more hydrophobic. The results of UV-vis absorption spectroscopy and CD spectra indicated that the secondary structure of CAT had been changed, and the amino acid residues were located in a more hydrophobic environment. Meanwhile, the UV-vis spectra indicated that the conformation of the heme porphyrin rings was changed. The microenvironment of CAT activity sites may be interfered by MWCNTs. This research showed that MWCNTs could not only contribute to the conformational changes of protein but also change the enzyme function.

  3. Investigation of the Interaction between Patulin and Human Serum Albumin by a Spectroscopic Method, Atomic Force Microscopy, and Molecular Modeling

    PubMed Central

    Yuqin, Li; Guirong, You; Zhen, Yang; Caihong, Liu; Baoxiu, Jia; Jiao, Chen; Yurong, Guo

    2014-01-01

    The interaction of patulin with human serum albumin (HSA) was studied in vitro under normal physiological conditions. The study was performed using fluorescence, ultraviolet-visible spectroscopy (UV-Vis), circular dichroism (CD), atomic force microscopy (AFM), and molecular modeling techniques. The quenching mechanism was investigated using the association constants, the number of binding sites, and basic thermodynamic parameters. A dynamic quenching mechanism occurred between HSA and patulin, and the binding constants (K) were 2.60 × 104, 4.59 × 104, and 7.01 × 104 M−1 at 288, 300, and 310 K, respectively. Based on fluorescence resonance energy transfer, the distance between the HSA and patulin was determined to be 2.847 nm. The ΔG0, ΔH0, and ΔS0 values across various temperatures indicated that hydrophobic interaction was the predominant binding force. The UV-Vis and CD results confirmed that the secondary structure of HSA was altered in the presence of patulin. The AFM results revealed that the individual HSA molecule dimensions were larger after interaction with patulin. In addition, molecular modeling showed that the patulin-HSA complex was stabilized by hydrophobic and hydrogen bond forces. The study results suggested that a weak intermolecular interaction occurred between patulin and HSA. Overall, the results are potentially useful for elucidating the toxigenicity of patulin when it is combined with the biomolecular function effect, transmembrane transport, toxicological, testing and other experiments. PMID:25110690

  4. Using Affinity Chromatography to Investigate Novel Protein–Protein Interactions in an Undergraduate Cell and Molecular Biology Lab Course

    PubMed Central

    2009-01-01

    Inquiry-driven lab exercises require students to think carefully about a question, carry out an investigation of that question, and critically analyze the results of their investigation. Here, we describe the implementation and assessment of an inquiry-based laboratory exercise in which students obtain and analyze novel data that contribute to our understanding of macromolecular trafficking between the nucleus and cytoplasm in eukaryotic cells. Although many of the proteins involved in nucleocytoplasmic transport are known, the physical interactions between some of these polypeptides remain uncharacterized. In this cell and molecular biology lab exercise, students investigate novel protein–protein interactions between factors involved in nuclear RNA export. Using recombinant protein expression, protein extraction, affinity chromatography, SDS-polyacrylamide gel electrophoresis, and Western blotting, undergraduates in a sophomore-level lab course identified a previously unreported association between the soluble mRNA transport factor Mex67 and the C-terminal region of the yeast nuclear pore complex protein Nup1. This exercise immersed students in the process of investigative science, from proposing and performing experiments through analyzing data and reporting outcomes. On completion of this investigative lab sequence, students reported enhanced understanding of the scientific process, increased proficiency with cellular and molecular methods and content, greater understanding of data analysis and the importance of appropriate controls, an enhanced ability to communicate science effectively, and an increased enthusiasm for scientific research and for the lab component of the course. The modular nature of this exercise and its focus on asking novel questions about protein–protein interactions make it easily transferable to undergraduate lab courses performed in a wide variety of contexts. PMID:19723816

  5. Interaction of human chymase with ginkgolides, terpene trilactones of Ginkgo biloba investigated by molecular docking simulations.

    PubMed

    Dubey, Amit; Marabotti, Anna; Ramteke, Pramod W; Facchiano, Angelo

    2016-04-29

    The search for natural chymase inhibitors has a good potential to provide a novel therapeutic approach against the cardiovascular diseases and other heart ailments. We selected from literature 20 promising Ginkgo biloba compounds, and tested them for their potential ability to bind chymase enzyme using docking and a deep analysis of surface pocket features. Docking results indicated that the compounds may interact with the active site of human chymase, with favorable distinct interactions with important residues Lys40, His57, Lys192, Phe191, Val146, Ser218, Gly216, and Ser195. In particular, proanthocyanidin is the one with the best-predicted binding energy, with seven hydrogen bonds. Interestingly, all active G. biloba compounds have formed the hydrogen bond interactions with the positively charged Lys192 residue at the active site, involved in the mechanism of pH enhancement for the cleavage of angiotensin I site. Ginkgolic acid and proanthocyanidin have better predicted binding energy towards chymase than other serine proteases, i.e kallikrein, tryptase and elastase, suggesting specificity for chymase inhibition. Our study suggests these G. biloba compounds are a promising starting point for developing chymase inhibitors for the potential development of future drugs.

  6. Interaction of human chymase with ginkgolides, terpene trilactones of Ginkgo biloba investigated by molecular docking simulations.

    PubMed

    Dubey, Amit; Marabotti, Anna; Ramteke, Pramod W; Facchiano, Angelo

    2016-04-29

    The search for natural chymase inhibitors has a good potential to provide a novel therapeutic approach against the cardiovascular diseases and other heart ailments. We selected from literature 20 promising Ginkgo biloba compounds, and tested them for their potential ability to bind chymase enzyme using docking and a deep analysis of surface pocket features. Docking results indicated that the compounds may interact with the active site of human chymase, with favorable distinct interactions with important residues Lys40, His57, Lys192, Phe191, Val146, Ser218, Gly216, and Ser195. In particular, proanthocyanidin is the one with the best-predicted binding energy, with seven hydrogen bonds. Interestingly, all active G. biloba compounds have formed the hydrogen bond interactions with the positively charged Lys192 residue at the active site, involved in the mechanism of pH enhancement for the cleavage of angiotensin I site. Ginkgolic acid and proanthocyanidin have better predicted binding energy towards chymase than other serine proteases, i.e kallikrein, tryptase and elastase, suggesting specificity for chymase inhibition. Our study suggests these G. biloba compounds are a promising starting point for developing chymase inhibitors for the potential development of future drugs. PMID:26975469

  7. Chemical and structural investigation of lipid nanoparticles: drug-lipid interaction and molecular distribution

    NASA Astrophysics Data System (ADS)

    Anantachaisilp, Suranan; Meejoo Smith, Siwaporn; Treetong, Alongkot; Pratontep, Sirapat; Puttipipatkhachorn, Satit; Rungsardthong Ruktanonchai, Uracha

    2010-03-01

    Lipid nanoparticles are a promising alternative to existing carriers in chemical or drug delivery systems. A key challenge is to determine how chemicals are incorporated and distributed inside nanoparticles, which assists in controlling chemical retention and release characteristics. This study reports the chemical and structural investigation of γ-oryzanol loading inside a model lipid nanoparticle drug delivery system composed of cetyl palmitate as solid lipid and Miglyol 812® as liquid lipid. The lipid nanoparticles were prepared by high pressure homogenization at varying liquid lipid content, in comparison with the γ-oryzanol free systems. The size of the lipid nanoparticles, as measured by the photon correlation spectroscopy, was found to decrease with increased liquid lipid content from 200 to 160 nm. High-resolution proton nuclear magnetic resonance (1H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmed successful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanning calorimetric and powder x-ray diffraction measurements provide complementary results to the 1H-NMR, whereby the crystallinity of the lipid nanoparticles diminishes with an increase in the liquid lipid content. For the distribution of γ-oryzanol inside the lipid nanoparticles, the 1H-NMR revealed that the chemical shifts of the liquid lipid in γ-oryzanol loaded systems were found at rather higher field than those in γ-oryzanol free systems, suggesting incorporation of γ-oryzanol in the liquid lipid. In addition, the phase-separated structure was observed by atomic force microscopy for lipid nanoparticles with 0% liquid lipid, but not for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopic and mapping measurements further revealed preferential incorporation of γ-oryzanol in the liquid part rather than the solid part of in the lipid nanoparticles. Simple models representing the distribution of γ-oryzanol and

  8. Does glimepiride alter the pharmacokinetics of sildenafil citrate in diabetic nephropathy animals: investigating mechanism of interaction by molecular modeling studies.

    PubMed

    Tripathi, Alok Shiomurti; Timiri, Ajay Kumar; Mazumder, Papiya Mitra; Chandewar, Anil

    2015-10-01

    The present study evaluates possible drug interactions between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ)-induced diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction based on molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg kg(-1), i.p.) and was confirmed by assessing blood and urine biochemical parameters 28 days after induction. Selected DN animals were used to explore the drug interaction between GLIM (0.5 mg kg(-1), p.o.) and SIL (2.5 mg kg(-1), p.o.) on the 29th and 70th day of the protocol. Possible drug interaction was assessed by evaluating the plasma drug concentration using HPLC-UV and changes in biochemical parameters in blood and urine were also determined. The mechanism of the interaction was postulated from the results of a molecular modeling study using the Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in blood and urine biochemical parameters in STZ-treated groups. The concentration of SIL increased significantly (P < 0.001) in rat plasma when co-administered with GLIM on the 70th day of the protocol. Molecular modeling revealed important interactions with rat serum albumin and CYP2C9. GLIM has a strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL, whereas for CYP2C9, GLIM forms a stronger hydrogen bond than SIL with polar contacts and hydrophobic interactions. The present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals, and the mechanism is supported by molecular modeling studies. PMID:26428531

  9. Interactive molecular dynamics

    NASA Astrophysics Data System (ADS)

    Schroeder, Daniel V.

    2015-03-01

    Physics students now have access to interactive molecular dynamics simulations that can model and animate the motions of hundreds of particles, such as noble gas atoms, that attract each other weakly at short distances but repel strongly when pressed together. Using these simulations, students can develop an understanding of forces and motions at the molecular scale, nonideal fluids, phases of matter, thermal equilibrium, nonequilibrium states, the Boltzmann distribution, the arrow of time, and much more. This article summarizes the basic features and capabilities of such a simulation, presents a variety of student exercises using it at the introductory and intermediate levels, and describes some enhancements that can further extend its uses. A working simulation code, in html5 and javascript for running within any modern Web browser, is provided as an online supplement.

  10. Molecular investigation of the interaction between ionic liquid type gemini surfactant and lysozyme: A spectroscopic and computational approach.

    PubMed

    Maurya, Jitendra Kumar; Mir, Muzaffar Ul Hassan; Singh, Upendra Kumar; Maurya, Neha; Dohare, Neeraj; Patel, Seema; Ali, Anwar; Patel, Rajan

    2015-07-01

    Herein, we are reporting the interaction of ionic liquid type gemini surfactant, 1,4-bis(3-dodecylimidazolium-1-yl) butane bromide ([C12-4-C12 im]Br2) with lysozyme by using Steady state fluorescence, UV-visible, Time resolved fluorescence, Fourier transform-infrared (FT-IR) spectroscopy techniques in combination with molecular modeling and docking method. The steady state fluorescence spectra suggested that the fluorescence of lysozyme was quenched by [C12-4-C12 im]Br2 through static quenching mechanism as confirmed by time resolved fluorescence spectroscopy. The binding constant for lysozyme-[C12-4-C12 im]Br2 interaction have been measured by UV-visible spectroscopy and found to be 2.541 × 10(5) M(-1). The FT-IR results show conformational changes in the secondary structure of lysozyme by the addition of [C12-4-C12 im]Br2. Moreover, the molecular docking study suggested that hydrogen bonding and hydrophobic interactions play a key role in the protein-surfactant binding. Additionally, the molecular dynamic simulation results revealed that the lysozyme-[C12-4-C12 im]Br2 complex reaches an equilibrium state at around 3 ns.

  11. Investigations on the Interactions of 5-Fluorouracil with Herring Sperm DNA: Steady State/Time Resolved and Molecular Modeling Studies

    NASA Astrophysics Data System (ADS)

    Chinnathambi, Shanmugavel; Karthikeyan, Subramani; Velmurugan, Devadasan; Hanagata, Nobutaka; Aruna, Prakasarao; Ganesan, Singaravelu

    2015-04-01

    In the present study, the interaction of 5-Fluorouracil with herring sperm DNA is reported using spectroscopic and molecular modeling techniques. This binding study of 5-FU with hs-DNA is of paramount importance in understanding chemico-biological interactions for drug design, pharmacy and biochemistry without altering the original structure. The challenge of the study was to find the exact binding mode of the drug 5-Fluorouracil with hs-DNA. From the absorption studies, a hyperchromic effect was observed for the herring sperm DNA in the presence of 5-Fluorouracil and a binding constant of 6.153 × 103 M-1 for 5-Fluorouracil reveals the existence of weak interaction between the 5-Fluorouracil and herring sperm DNA. Ethidium bromide loaded herring sperm DNA showed a quenching in the fluorescence intensity after the addition of 5-Fluorouracil. The binding constants for 5-Fluorouracil stranded DNA and competitive bindings of 5-FU interacting with DNA-EB systems were examined by fluorescence spectra. The Stern-Volmer plots and fluorescence lifetime results confirm the static quenching nature of the drug-DNA complex. The binding constant Kb was 2.5 × 104 L mol-1 and the number of binding sites are 1.17. The 5-FU on DNA system was calculated using double logarithmic plot. From the Forster nonradiative energy transfer study it has been found that the distance of 5-FU from DNA was 4.24 nm. In addition to the spectroscopic results, the molecular modeling studies also revealed the major groove binding as well as the partial intercalation mode of binding between the 5-Fluorouracil and herring sperm DNA. The binding energy and major groove binding as -6.04 kcal mol-1 and -6.31 kcal mol-1 were calculated from the modeling studies. All the testimonies manifested that binding modes between 5-Fluorouracil and DNA were evidenced to be groove binding and in partial intercalative mode.

  12. Investigation of allosteric modulation mechanism of metabotropic glutamate receptor 1 by molecular dynamics simulations, free energy and weak interaction analysis

    NASA Astrophysics Data System (ADS)

    Bai, Qifeng; Yao, Xiaojun

    2016-02-01

    Metabotropic glutamate receptor 1 (mGlu1), which belongs to class C G protein-coupled receptors (GPCRs), can be coupled with G protein to transfer extracellular signal by dimerization and allosteric regulation. Unraveling the dimer packing and allosteric mechanism can be of great help for understanding specific regulatory mechanism and designing more potential negative allosteric modulator (NAM). Here, we report molecular dynamics simulation studies of the modulation mechanism of FITM on the wild type, T815M and Y805A mutants of mGlu1 through weak interaction analysis and free energy calculation. The weak interaction analysis demonstrates that van der Waals (vdW) and hydrogen bonding play an important role on the dimer packing between six cholesterol molecules and mGlu1 as well as the interaction between allosteric sites T815, Y805 and FITM in wild type, T815M and Y805A mutants of mGlu1. Besides, the results of free energy calculations indicate that secondary binding pocket is mainly formed by the residues Thr748, Cys746, Lys811 and Ser735 except for FITM-bound pocket in crystal structure. Our results can not only reveal the dimer packing and allosteric regulation mechanism, but also can supply useful information for the design of potential NAM of mGlu1.

  13. Synthesis of new molecular probes for investigation of steroid biosynthesis induced by selective interaction with peripheral type benzodiazepine receptors (PBR).

    PubMed

    Campiani, Giuseppe; Ramunno, Anna; Fiorini, Isabella; Nacci, Vito; Morelli, Elena; Novellino, Ettore; Goegan, Mara; Mennini, Tiziana; Sullivan, Stephen; Zisterer, Daniela M; Williams, Clive D

    2002-09-12

    In the present study, we have synthesized and tested novel pyridopyrrolo- and pyrrolobenzoxazepine derivatives, as novel and selective peripheral type benzodiazepine receptor (PBR) ligands, and their ability to modulate steroid biosynthesis has been investigated. A subset of new ligands bind the PBR (rat brain and testis) with picomolar affinity, representing the most potent ligands that have been identified to date, and elicited effects on endogenous rate of steroidogenesis in MA10 Leydig cells, having similar potency and effect as PK11195. Several compounds, differently substituted at C-7, were used as molecular yardsticks to probe the spatial dimension of the lipophilic pocket L4 in the receptor binding site.

  14. Investigation of molecular interactions between β-lactoglobulin and sugar beet pectin by multi-detection HPSEC.

    PubMed

    Qi, Phoebe X; Chau, Hoa K; Fishman, Marshall L; Wickham, Edward D; Hotchkiss, Arland T

    2014-07-17

    Molecular interactions between β-lactoglobulin (β-LG) and sugar beet pectin (SBP) were studied using online multi-detection high performance size exclusion chromatography (HPSEC) at neutral pH and 50mM ionic strength. The hydrodynamic properties of various interacting polymer fractions were characterized in detail and compared with those of β-LG and SBP. Results showed that ∼6.5% (w/w) of native dimeric β-LG molecules formed complexes with over 35% SBP molecules of varying sizes, 800, 110 and 75 kDa. Although the β-LG molecules bind to SBP molecules of all sizes and shapes, they tend to favor the intermediate (110 kDa) and small sized (75 kDa) SBP molecules. All resulting complexes possess altered shapes and hydrodynamic properties when compared to unbound SBP and β-LG. About half of the interacting β-LG (∼3.5%) molecules were thought to bind to a small amount of non-covalently bound feruloyl groups, possibly present in SBP. When pre-heat treated β-LG and SBP were combined, more than 16% of β-LG formed complexes with at least 45% of SBP molecules of varying sizes, Mw∼750-800, 110, and 55-80 kDa. The complexes formed between β-LG aggregates and/or oligomers and the large SBP molecules (750-800 kDa) adopt the shape of β-LG aggregates, random coil. Both groups of complexes formed between β-LG intermediate (110 kDa) and small sized (55-80 kDa) SBP take on the shape of rigid rod. It was speculated that half of the interacting heat-treated β-LG molecules (∼8%) are complexed with non-covalently bound feruloyl groups in SBP.

  15. Electrostatic interactions in molecular materials

    NASA Astrophysics Data System (ADS)

    Painelli, Anna; Terenziani, Francesca

    2004-03-01

    Non-additive collective behavior appears in molecular materials as a result of intermolecular interactions. We present a model for interacting polar and polarizable molecules that applies to different supramolecular architectures of donor-π-acceptor molecules. We follow a bottom-up modeling strategy: the detailed analysis of spectroscopic data of solvated molecules leads to the definition of a simple two-state model for the molecular units. Classical electrostatic interactions are then introduced to model molecular clusters. The molecular properties are strickingly affected by supramolecular interactions, as demonstrated by spectroscopic studies. Brand new phenomena, like phase transitions and multielectron transfer, with no counterpart at the molecular level are observed as direct consequences of electrostatic intermolecular interactions.

  16. Intramolecular interactions stabilizing compact conformations of the intrinsically disordered kinase-inhibitor domain of Sic1: a molecular dynamics investigation

    PubMed Central

    Lambrughi, Matteo; Papaleo, Elena; Testa, Lorenzo; Brocca, Stefania; De Gioia, Luca; Grandori, Rita

    2012-01-01

    Cyclin-dependent kinase inhibitors (CKIs) are key regulatory proteins of the eukaryotic cell cycle, which modulate cyclin-dependent kinase (Cdk) activity. CKIs perform their inhibitory effect by the formation of ternary complexes with a target kinase and its cognate cyclin. These regulators generally belong to the class of intrinsically disordered proteins (IDPs), which lack a well-defined and organized three-dimensional (3D) structure in their free state, undergoing folding upon binding to specific partners. Unbound IDPs are not merely random-coil structures, but can present intrinsically folded structural units (IFSUs) and collapsed conformations. These structural features can be relevant to protein function in vivo. The yeast CKI Sic1 is a 284-amino acid IDP that binds to Cdk1 in complex with the Clb5,6 cyclins, preventing phosphorylation of G1 substrates and, therefore, entrance to the S phase. Sic1 degradation, triggered by multiple phosphorylation events, promotes cell-cycle progression. Previous experimental studies pointed out a propensity of Sic1 and its isolated domains to populate both extended and compact conformations. The present contribution provides models for compact conformations of the Sic1 kinase-inhibitory domain (KID) by all-atom molecular dynamics (MD) simulations in explicit solvent and in the absence of interactors. The results are integrated by spectroscopic and spectrometric data. Helical IFSUs are identified, along with networks of intramolecular interactions. The results identify a group of putative hub residues and networks of electrostatic interactions, which are likely to be involved in the stabilization of the globular states. PMID:23189058

  17. Effect of Red Clover on CYP Expression: An Investigation of Herb-Drug Interaction at Molecular Level

    PubMed Central

    Tripathi, Anubhuti; Singh, S. P.; Raju, K. S. R.; Wahajuddin; Gayen, J. R

    2014-01-01

    Hormone replacement therapy and selective estrogen receptor modulator are the most common therapy for women going through menopause. These therapies though popular fail to relieve withdrawal symptoms such as hot flashes, fatigue, leg cramps and nausea. This scenario necessitates to herbal preparations as alternative which may lead to simultaneous intake of herbal preparations, containing flavonoids, as well as Selective estrogen receptor modulator hence creating a phenomenon of herb drug interaction. Here we investigate the effect of red clover on steady state mRNA levels of rat cytochrome P 450 enzymes. Further, red clover's effect on cytochrome P 450's expression has been investigated when co-administered with tamoxifen and raloxifene. Exposure to red clover resulted in significant down regulation of all the cytochrome P 450 isoform mRNA except cytochrome P 450 2C13 and cytochrome P 450 3A2. When red clover is given in combination with tamoxifen or raloxifene altered level of cytochrome P 450 enzyme mRNA is observed. Present results suggest that herbal medical preparations such red clover has potential for herb drug interaction. PMID:25035541

  18. MDM2–MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance

    PubMed Central

    Moscetti, Ilaria; Teveroni, Emanuela; Moretti, Fabiola; Bizzarri, Anna Rita; Cannistraro, Salvatore

    2016-01-01

    Murine double minute 2 (MDM2) and 4 (MDM4) are known as the main negative regulators of p53, a tumor suppressor. They are able to form heterodimers that are much more effective in the downregulation of p53. Therefore, the MDM2–MDM4 complex could be a target for promising therapeutic restoration of p53 function. To this aim, a deeper understanding of the molecular mechanisms underlining the heterodimerization is needed. The kinetic and thermodynamic characterization of the MDM2–MDM4 complex was performed with two complementary approaches: atomic force spectroscopy and surface plasmon resonance. Both techniques revealed an equilibrium dissociation constant (KD) in the micromolar range for the MDM2–MDM4 heterodimer, similar to related complexes involved in the p53 network. Furthermore, the MDM2–MDM4 complex is characterized by a relatively high free energy, through a single energy barrier, and by a lifetime in the order of tens of seconds. New insights into the MDM2–MDM4 interaction could be highly important for developing innovative anticancer drugs focused on p53 reactivation. PMID:27621617

  19. MDM2–MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance

    PubMed Central

    Moscetti, Ilaria; Teveroni, Emanuela; Moretti, Fabiola; Bizzarri, Anna Rita; Cannistraro, Salvatore

    2016-01-01

    Murine double minute 2 (MDM2) and 4 (MDM4) are known as the main negative regulators of p53, a tumor suppressor. They are able to form heterodimers that are much more effective in the downregulation of p53. Therefore, the MDM2–MDM4 complex could be a target for promising therapeutic restoration of p53 function. To this aim, a deeper understanding of the molecular mechanisms underlining the heterodimerization is needed. The kinetic and thermodynamic characterization of the MDM2–MDM4 complex was performed with two complementary approaches: atomic force spectroscopy and surface plasmon resonance. Both techniques revealed an equilibrium dissociation constant (KD) in the micromolar range for the MDM2–MDM4 heterodimer, similar to related complexes involved in the p53 network. Furthermore, the MDM2–MDM4 complex is characterized by a relatively high free energy, through a single energy barrier, and by a lifetime in the order of tens of seconds. New insights into the MDM2–MDM4 interaction could be highly important for developing innovative anticancer drugs focused on p53 reactivation.

  20. Detection of molecular interactions

    DOEpatents

    Groves, John T.; Baksh, Michael M.; Jaros, Michal

    2012-02-14

    A method and assay are described for measuring the interaction between a ligand and an analyte. The assay can include a suspension of colloidal particles that are associated with a ligand of interest. The colloidal particles are maintained in the suspension at or near a phase transition state from a condensed phase to a dispersed phase. An analyte to be tested is then added to the suspension. If the analyte binds to the ligand, a phase change occurs to indicate that the binding was successful.

  1. Interaction of O and OH radicals with a simple model system for lipids in the skin barrier: a reactive molecular dynamics investigation for plasma medicine

    NASA Astrophysics Data System (ADS)

    Van der Paal, Jonas; Aernouts, Stefaan; van Duin, Adri C. T.; Neyts, Erik C.; Bogaerts, Annemie

    2013-10-01

    Plasma medicine has been claimed to provide a novel route to heal wounds and regenerate skin, although very little is currently known about the elementary processes taking place. We carried out a series of ReaxFF-based reactive molecular dynamics simulations to investigate the interaction of O and OH radicals with lipids, more specifically with α-linolenic acid as a model for the free fatty acids present in the upper skin layer. Our calculations predict that the O and OH radicals most typically abstract a H atom from the fatty acids, which can lead to the formation of a conjugated double bond, but also to the incorporation of alcohol or aldehyde groups, thereby increasing the hydrophilic character of the fatty acids and changing the general lipid composition of the skin. Within the limitations of the investigated model, no formation of possibly toxic products was observed.

  2. Using Affinity Chromatography to Investigate Novel Protein-Protein Interactions in an Undergraduate Cell and Molecular Biology Lab Course

    ERIC Educational Resources Information Center

    Belanger, Kenneth D.

    2009-01-01

    Inquiry-driven lab exercises require students to think carefully about a question, carry out an investigation of that question, and critically analyze the results of their investigation. Here, we describe the implementation and assessment of an inquiry-based laboratory exercise in which students obtain and analyze novel data that contribute to our…

  3. How to Predict Molecular Interactions between Species?

    PubMed Central

    Schulze, Sylvie; Schleicher, Jana; Guthke, Reinhard; Linde, Jörg

    2016-01-01

    Organisms constantly interact with other species through physical contact which leads to changes on the molecular level, for example the transcriptome. These changes can be monitored for all genes, with the help of high-throughput experiments such as RNA-seq or microarrays. The adaptation of the gene expression to environmental changes within cells is mediated through complex gene regulatory networks. Often, our knowledge of these networks is incomplete. Network inference predicts gene regulatory interactions based on transcriptome data. An emerging application of high-throughput transcriptome studies are dual transcriptomics experiments. Here, the transcriptome of two or more interacting species is measured simultaneously. Based on a dual RNA-seq data set of murine dendritic cells infected with the fungal pathogen Candida albicans, the software tool NetGenerator was applied to predict an inter-species gene regulatory network. To promote further investigations of molecular inter-species interactions, we recently discussed dual RNA-seq experiments for host-pathogen interactions and extended the applied tool NetGenerator (Schulze et al., 2015). The updated version of NetGenerator makes use of measurement variances in the algorithmic procedure and accepts gene expression time series data with missing values. Additionally, we tested multiple modeling scenarios regarding the stimuli functions of the gene regulatory network. Here, we summarize the work by Schulze et al. (2015) and put it into a broader context. We review various studies making use of the dual transcriptomics approach to investigate the molecular basis of interacting species. Besides the application to host-pathogen interactions, dual transcriptomics data are also utilized to study mutualistic and commensalistic interactions. Furthermore, we give a short introduction into additional approaches for the prediction of gene regulatory networks and discuss their application to dual transcriptomics data. We

  4. Molecular Soybean-Pathogen Interactions.

    PubMed

    Whitham, Steven A; Qi, Mingsheng; Innes, Roger W; Ma, Wenbo; Lopes-Caitar, Valéria; Hewezi, Tarek

    2016-08-01

    Soybean hosts a wide variety of pathogens that cause significant yield losses. The importance of soybean as a major oilseed crop has led to research focused on its interactions with pathogens, such as Soybean mosaic virus, Pseudomonas syringae, Phytophthora sojae, Phakopsora pachyrhizi, and Heterodera glycines. Pioneering work on soybean's interactions with these organisms, which represent the five major pathogen groups (viruses, bacteria, oomycetes, fungi, and nematodes), has contributed to our understanding of the molecular mechanisms underlying virulence and immunity. These mechanisms involve conserved and unique features that validate the need for research in both soybean and homologous model systems. In this review, we discuss identification of effectors and their functions as well as resistance gene-mediated recognition and signaling. We also point out areas in which model systems and recent advances in resources and tools have provided opportunities to gain deeper insights into soybean-pathogen interactions. PMID:27359370

  5. NMR investigations of molecular dynamics

    NASA Astrophysics Data System (ADS)

    Palmer, Arthur

    2011-03-01

    NMR spectroscopy is a powerful experimental approach for characterizing protein conformational dynamics on multiple time scales. The insights obtained from NMR studies are complemented and by molecular dynamics (MD) simulations, which provide full atomistic details of protein dynamics. Homologous mesophilic (E. coli) and thermophilic (T. thermophilus) ribonuclease H (RNase H) enzymes serve to illustrate how changes in protein sequence and structure that affect conformational dynamic processes can be monitored and characterized by joint analysis of NMR spectroscopy and MD simulations. A Gly residue inserted within a putative hinge between helices B and C is conserved among thermophilic RNases H, but absent in mesophilic RNases H. Experimental spin relaxation measurements show that the dynamic properties of T. thermophilus RNase H are recapitulated in E. coli RNase H by insertion of a Gly residue between helices B and C. Additional specific intramolecular interactions that modulate backbone and sidechain dynamical properties of the Gly-rich loop and of the conserved Trp residue flanking the Gly insertion site have been identified using MD simulations and subsequently confirmed by NMR spin relaxation measurements. These results emphasize the importance of hydrogen bonds and local steric interactions in restricting conformational fluctuations, and the absence of such interactions in allowing conformational adaptation to substrate binding.

  6. Interactive Modelling of Molecular Structures

    NASA Astrophysics Data System (ADS)

    Rustad, J. R.; Kreylos, O.; Hamann, B.

    2004-12-01

    The "Nanotech Construction Kit" (NCK) [1] is a new project aimed at improving the understanding of molecular structures at a nanometer-scale level by visualization and interactive manipulation. Our very first prototype is a virtual-reality program allowing the construction of silica and carbon structures from scratch by assembling them one atom at a time. In silica crystals or glasses, the basic building block is an SiO4 unit, with the four oxygen atoms arranged around the central silicon atom in the shape of a regular tetrahedron. Two silicate units can connect to each other by their silicon atoms covalently bonding to one shared oxygen atom. Geometrically, this means that two tetrahedra can link at their vertices. Our program is based on geometric representations and uses simple force fields to simulate the interaction of building blocks, such as forming/breaking of bonds and repulsion. Together with stereoscopic visualization and direct manipulation of building blocks using wands or data gloves, this enables users to create realistic and complex molecular models in short amounts of time. The NCK can either be used as a standalone tool, to analyze or experiment with molecular structures, or it can be used in combination with "traditional" molecular dynamics (MD) simulations. In a first step, the NCK can create initial configurations for subsequent MD simulation. In a more evolved setup, the NCK can serve as a visual front-end for an ongoing MD simulation, visualizing changes in simulation state in real time. Additionally, the NCK can be used to change simulation state on-the-fly, to experiment with different simulation conditions, or force certain events, e.g., the forming of a bond, and observe the simulation's reaction. [1] http://graphics.cs.ucdavis.edu/~okreylos/ResDev/NanoTech

  7. Decoding molecular interactions in microbial communities.

    PubMed

    Abreu, Nicole A; Taga, Michiko E

    2016-09-01

    Microbial communities govern numerous fundamental processes on earth. Discovering and tracking molecular interactions among microbes is critical for understanding how single species and complex communities impact their associated host or natural environment. While recent technological developments in DNA sequencing and functional imaging have led to new and deeper levels of understanding, we are limited now by our inability to predict and interpret the intricate relationships and interspecies dependencies within these communities. In this review, we highlight the multifaceted approaches investigators have taken within their areas of research to decode interspecies molecular interactions that occur between microbes. Understanding these principles can give us greater insight into ecological interactions in natural environments and within synthetic consortia. PMID:27417261

  8. Investigating the Conformational Structure and Potential Site Interactions of SOD Inhibitors on Ec-SOD in Marine Mud Crab Scylla serrata: A Molecular Modeling Approach.

    PubMed

    Paital, Biswaranjan; Sablok, Gaurav; Kumar, Sunil; Singh, Sanjeev Kumar; Chainy, G B N

    2016-09-01

    Superoxide dismutases (SODs) act as a first line of the enzymatic antioxidant defense system to control cellular superoxide anion toxicity. Previously, several inhibitors have been widely identified and catalogued for inhibition of SOD activity; however, still the information about the mechanism of interaction and points toward the inhibitor interactions in structures of SODs in general and in extracellular (Ec)-SOD in particular is still in naive. In the present research, we present an insight to elucidate the molecular basis of interactions of SOD inhibitors with Ec-SOD in mud crab Scylla serrata using molecular modeling and docking approaches. Different inhibitors of SOD such as hydrogen peroxide [Formula: see text], potassium cyanide, sodium dodecyl sulfate (SDS), [Formula: see text]-mercaptoethanol and dithiocarbamate were screened to understand the potential sites that may act as sites for cleavage or blocking in the protein. SOD-SDS and [Formula: see text] complex interactions indicate residues Pro72 and Asp102 of the predicted crab Ec-SOD as common targets. The GOLD result indicates that Pro72, Asp102 and Thr103 are commonly acting as the site of interaction in Ec-SOD of S. serrata with SOD inhibitors. For the first time, the results of this study provide an insight into the structural properties of Ec-SOD of S. serrata and define the possible involvements between the amino acids present in its active sites, i.e., in the regions from 70 to 84 and from 101 to 103 and different inhibitors.

  9. Investigation of the Coupled Effects of Molecular Weight and Charge-Transfer Interactions on the Optical and Photochemical Properties of Dissolved Organic Matter.

    PubMed

    McKay, Garrett; Couch, Kylie D; Mezyk, Stephen P; Rosario-Ortiz, Fernando L

    2016-08-01

    We studied the formation of photochemically produced reactive intermediates (RI) from dissolved organic matter (DOM). Specifically, we focused on the effects of variable molecular weight and chemical reduction on the optical properties of DOM (absorbance and fluorescence) and the formation of singlet oxygen ((1)O2), DOM triplet excited states ((3)DOM*), and the hydroxyl radical ((•)OH). The data are largely evaluated in terms of a charge-transfer (CT) model, but deficiencies in the model to explain the data are pointed out when evident. A total of two sets of samples were studied that were subjected to different treatments; the first set included secondary-treated wastewaters and a wastewater-impacted stream, and the second was a DOM isolate. Treatments included size fractionation and chemical reduction using sodium borohydride. Taken as a whole, the results demonstrate that decreasing molecular weight and borohydride reduction work in opposition regarding quantum efficiencies for (1)O2 and (3)DOM* production but in concert for fluorescence and (•)OH production. The optical and photochemical data provide evidence for a limited role of CT interactions occurring in lower-molecular-weight DOM molecules. In addition, the data suggest that the observed optical and photochemical properties of DOM are a result of multiple populations of chromophores and that their relative contribution is changed by molecular-weight fractionation and borohydride reduction.

  10. Interaction of vitamin B1 with bovine serum albumin investigation using vitamin B1-selective electrode: potentiometric and molecular modeling study.

    PubMed

    Hosseinzadeh, Reza; Khorsandi, Khatereh

    2016-09-01

    Vitamin B1 or thiamin is one of the B vitamins. All B vitamins help the body to convert food (carbohydrates) into fuel (glucose), which produces energy. The B vitamins are necessary for healthy skin, eyes, hair, and liver. It also could help the nervous system function properly, and is necessary for brain functions. Drug interactions with protein can affect the distribution of the drug and eliminate the drug in living systems. In this study, the binding of thiamine hydrochloride (vitamin B1) to bovine serum albumin (BSA) was evaluated using a new proposed vitamin B1 (thiamine)-selective membrane electrode under various experimental conditions, such as pH, ionic strength, and protein concentration; in addition molecular modeling was applied as well. The binding isotherms plotted based on potentiometric data and analyzed using the Wyman binding potential concept. The apparent binding constant was determined and used for the calculation of intrinsic Gibbs free energy of binding. According to the electrochemical and molecular docking results, it can be concluded that the hydrophobic interactions and hydrogen binding are major interactions between BSA and vitamin B1.

  11. Interaction of vitamin B1 with bovine serum albumin investigation using vitamin B1-selective electrode: potentiometric and molecular modeling study.

    PubMed

    Hosseinzadeh, Reza; Khorsandi, Khatereh

    2016-09-01

    Vitamin B1 or thiamin is one of the B vitamins. All B vitamins help the body to convert food (carbohydrates) into fuel (glucose), which produces energy. The B vitamins are necessary for healthy skin, eyes, hair, and liver. It also could help the nervous system function properly, and is necessary for brain functions. Drug interactions with protein can affect the distribution of the drug and eliminate the drug in living systems. In this study, the binding of thiamine hydrochloride (vitamin B1) to bovine serum albumin (BSA) was evaluated using a new proposed vitamin B1 (thiamine)-selective membrane electrode under various experimental conditions, such as pH, ionic strength, and protein concentration; in addition molecular modeling was applied as well. The binding isotherms plotted based on potentiometric data and analyzed using the Wyman binding potential concept. The apparent binding constant was determined and used for the calculation of intrinsic Gibbs free energy of binding. According to the electrochemical and molecular docking results, it can be concluded that the hydrophobic interactions and hydrogen binding are major interactions between BSA and vitamin B1. PMID:26372107

  12. Investigation into the interaction of losartan with human serum albumin and glycated human serum albumin by spectroscopic and molecular dynamics simulation techniques: A comparison study.

    PubMed

    Moeinpour, Farid; Mohseni-Shahri, Fatemeh S; Malaekeh-Nikouei, Bizhan; Nassirli, Hooriyeh

    2016-09-25

    The interaction between losartan and human serum albumin (HSA), as well as its glycated form (gHSA) was studied by multiple spectroscopic techniques and molecular dynamics simulation under physiological conditions. The binding information, including the binding constants, effective quenching constant and number of binding sites showed that the binding partiality of losartan to HSA was higher than to gHSA. The findings of three-dimensional fluorescence spectra demonstrated that the binding of losartan to HSA and gHSA would alter the protein conformation. The distances between Trp residue and the binding sites of the drug were evaluated on the basis of the Förster theory, and it was indicated that non-radiative energy transfer from HSA and gHSA to the losartan happened with a high possibility. According to molecular dynamics simulation, the protein secondary and tertiary structure changes were compared in HSA and gHSA for clarifying the obtained results.

  13. Spin–orbit interaction mediated molecular dissociation

    SciTech Connect

    Kokkonen, E. Jänkälä, K.; Kettunen, J. A.; Heinäsmäki, S.; Karpenko, A.; Huttula, M.; Löytynoja, T.

    2014-05-14

    The effect of the spin–orbit interaction to photofragmentation is investigated in the mercury(II) bromide (HgBr{sub 2}) molecule. Changes in the fragmentation between the two spin–orbit components of Hg 5d photoionization, as well as within the molecular-field-splitted levels of these components are observed. Dissociation subsequent to photoionization is studied with synchrotron radiation and photoelectron-photoion coincidence spectroscopy. The experimental results are accompanied by relativistic ab initio analysis of the photoelectron spectrum.

  14. An investigation on the interaction modes of a single-strand DNA aptamer and RBP4 protein: a molecular dynamic simulations approach.

    PubMed

    Torabi, Raheleh; Bagherzadeh, Kowsar; Ghourchian, Hedayatollah; Amanlou, Massoud

    2016-09-14

    Type two diabetes is one of the primary health issues threatening public well-being worldwide. One of the pre-diagnosis biomarkers of this disease, retinol binding protein 4 (RBP4), has been demonstrated to be detected with a 76-mer ssDNA aptamer instead of conventional antibodies. However, there is no structural information on the RBP4 binding aptamer (RBA) and the mechanism of its binding to RBP4 still remains unexplored. The objective of the present study is to achieve a better understanding of specific binding interactions of the target protein (RBP4) and RBA, employing Molecular Dynamics simulations (MDs) to provide detailed information on fluctuations, conformational changes, critical bases and effective forces to develop regulated aptamers to be employed in designing new aptamers for many useful recognition applications. RBA was designed according to its reported base pair sequence and secondary structure. The HADDOCK on line docking program was used to predict a suitable RBP4-RBA mode of interaction to start MDs with. MDs methodology was used to analyze the final complex stability and detect interacting residues. Eventually, we conclude that single strand located bases are the key components that conduct the intercalation phenomenon with big targets rather than those involving loops and folded motifs, to encompass targets and probably inhibit their activity. Also, UV-visible, circular dichroism and fluorescence spectroscopy measurements confirmed the interactions between RBA and RBP4 and RBP4-RBA complex formation.

  15. An investigation on the interaction modes of a single-strand DNA aptamer and RBP4 protein: a molecular dynamic simulations approach.

    PubMed

    Torabi, Raheleh; Bagherzadeh, Kowsar; Ghourchian, Hedayatollah; Amanlou, Massoud

    2016-09-14

    Type two diabetes is one of the primary health issues threatening public well-being worldwide. One of the pre-diagnosis biomarkers of this disease, retinol binding protein 4 (RBP4), has been demonstrated to be detected with a 76-mer ssDNA aptamer instead of conventional antibodies. However, there is no structural information on the RBP4 binding aptamer (RBA) and the mechanism of its binding to RBP4 still remains unexplored. The objective of the present study is to achieve a better understanding of specific binding interactions of the target protein (RBP4) and RBA, employing Molecular Dynamics simulations (MDs) to provide detailed information on fluctuations, conformational changes, critical bases and effective forces to develop regulated aptamers to be employed in designing new aptamers for many useful recognition applications. RBA was designed according to its reported base pair sequence and secondary structure. The HADDOCK on line docking program was used to predict a suitable RBP4-RBA mode of interaction to start MDs with. MDs methodology was used to analyze the final complex stability and detect interacting residues. Eventually, we conclude that single strand located bases are the key components that conduct the intercalation phenomenon with big targets rather than those involving loops and folded motifs, to encompass targets and probably inhibit their activity. Also, UV-visible, circular dichroism and fluorescence spectroscopy measurements confirmed the interactions between RBA and RBP4 and RBP4-RBA complex formation. PMID:27511589

  16. Spectroscopic and molecular modeling methods to investigate the interaction between 5-Hydroxymethyl-2-furfural and calf thymus DNA using ethidium bromide as a probe.

    PubMed

    Zhu, Jinhua; Chen, Lanlan; Dong, Yingying; Li, Jiazhong; Liu, Xiuhua

    2014-04-24

    In this work, the interaction of 5-Hydroxymethyl-2-furfural (5-HMF) with calf thymus DNA (ctDNA) under simulated physiological conditions (Tris-HCl buffer of pH 7.40), was explored by UV absorption spectroscopy, fluorescence spectroscopy and molecular modeling method, using ethidium bromide (EB) as a fluorescence probe of DNA. The fluorescence quenching mechanism of EB-ctDNA by 5-HMF was confirmed to be a static quenching, which derived from the formation of a new complex. The binding constants of 5-HMF with DNA in the presence of EB were calculated to be 2.17×10(3), 4.24×10(3) and 6.95×10(3) L mol(-1) at 300, 305 and 310 K, respectively. The calculated thermodynamic parameters, enthalpy change ΔH and entropy change ΔS, suggested that both hydrophobic interactions and hydrogen bonds played a predominant role in the binding of 5-HMF to DNA. According to the UV absorption spectroscopy and melting temperature (Tm) curve results, the binding mode of 5-HMF with DNA was indicative of a non-intercalative binding, which was supposed to be a groove binding. The molecular modeling results showed that 5-HMF could bind into the hydrophobic region of ctDNA and supported the conclusions obtained from the above experiments.

  17. Molecular mechanisms of membrane interaction at implantation.

    PubMed

    Davidson, Lien M; Coward, Kevin

    2016-03-01

    Successful pregnancy is dependent upon the implantation of a competent embryo into a receptive endometrium. Despite major advancement in our understanding of reproductive medicine over the last few decades, implantation failure still occurs in both normal pregnancies and those created artificially by assisted reproductive technology (ART). Consequently, there is significant interest in elucidating the etiology of implantation failure. The complex multistep process of implantation begins when the developing embryo first makes contact with the plasma membrane of epithelial cells within the uterine environment. However, although this biological interaction marks the beginning of a fundamental developmental process, our knowledge of the intricate physiological and molecular processes involved remains sparse. In this synopsis, we aim to provide an overview of our current understanding of the morphological changes which occur to the plasma membrane of the uterine endothelium, and the molecular mechanisms that control communication between the early embryo and the endometrium during implantation. A multitude of molecular factors have been implicated in this complex process, including endometrial integrins, extracellular matrix molecules, adhesion molecules, growth factors, and ion channels. We also explore the development of in vitro models for embryo implantation to help researchers investigate mechanisms which may underlie implantation failure. Understanding the precise molecular pathways associated with implantation failure could help us to generate new prognostic/diagnostic biomarkers, and may identify novel therapeutic targets. PMID:26969610

  18. MINT: a Molecular INTeraction database.

    PubMed

    Zanzoni, Andreas; Montecchi-Palazzi, Luisa; Quondam, Michele; Ausiello, Gabriele; Helmer-Citterich, Manuela; Cesareni, Gianni

    2002-02-20

    Protein interaction databases represent unique tools to store, in a computer readable form, the protein interaction information disseminated in the scientific literature. Well organized and easily accessible databases permit the easy retrieval and analysis of large interaction data sets. Here we present MINT, a database (http://cbm.bio.uniroma2.it/mint/index.html) designed to store data on functional interactions between proteins. Beyond cataloguing binary complexes, MINT was conceived to store other types of functional interactions, including enzymatic modifications of one of the partners. Release 1.0 of MINT focuses on experimentally verified protein-protein interactions. Both direct and indirect relationships are considered. Furthermore, MINT aims at being exhaustive in the description of the interaction and, whenever available, information about kinetic and binding constants and about the domains participating in the interaction is included in the entry. MINT consists of entries extracted from the scientific literature by expert curators assisted by 'MINT Assistant', a software that targets abstracts containing interaction information and presents them to the curator in a user-friendly format. The interaction data can be easily extracted and viewed graphically through 'MINT Viewer'. Presently MINT contains 4568 interactions, 782 of which are indirect or genetic interactions.

  19. Molecular assembly of superquenchers in signaling molecular interactions.

    PubMed

    Yang, Chaoyong James; Lin, Hui; Tan, Weihong

    2005-09-21

    We have designed a novel molecular assembly of quencher molecules to form superquenchers with excellent quenching efficiency. The superquencher can be engineered as desired by assembling different types and different numbers of quencher molecules. By labeling a superquencher to a molecular beacon, a 320-fold enhancement of fluorescent signal was achieved, compared to about 14-fold from a molecular beacon prepared with the same monomer quencher. Our molecular assembly approach can effectively improve the sensitivity of a variety of fluorescent assays and can be widely useful for molecular interaction studies.

  20. 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…

  1. Theoretical studies of molecular interactions

    SciTech Connect

    Lester, W.A. Jr.

    1993-12-01

    This research program is directed at extending fundamental knowledge of atoms and molecules including their electronic structure, mutual interaction, collision dynamics, and interaction with radiation. The approach combines the use of ab initio methods--Hartree-Fock (HF) multiconfiguration HF, configuration interaction, and the recently developed quantum Monte Carlo (MC)--to describe electronic structure, intermolecular interactions, and other properties, with various methods of characterizing inelastic and reaction collision processes, and photodissociation dynamics. Present activity is focused on the development and application of the QMC method, surface catalyzed reactions, and reorientation cross sections.

  2. Theoretical Analysis of Dynamic Processes for Interacting Molecular Motors

    PubMed Central

    Teimouri, Hamid; Kolomeisky, Anatoly B.; Mehrabiani, Kareem

    2015-01-01

    Biological transport is supported by collective dynamics of enzymatic molecules that are called motor proteins or molecular motors. Experiments suggest that motor proteins interact locally via short-range potentials. We investigate the fundamental role of these interactions by analyzing a new class of totally asymmetric exclusion processes where interactions are accounted for in a thermodynamically consistent fashion. It allows us to connect explicitly microscopic features of motor proteins with their collective dynamic properties. Theoretical analysis that combines various mean-field calculations and computer simulations suggests that dynamic properties of molecular motors strongly depend on interactions, and correlations are stronger for interacting motor proteins. Surprisingly, it is found that there is an optimal strength of interactions (weak repulsion) that leads to a maximal particle flux. It is also argued that molecular motors transport is more sensitive to attractive interactions. Applications of these results for kinesin motor proteins are discussed. PMID:25688287

  3. Uranyl ion interaction at the water/NiO(100) interface: A predictive investigation by first-principles molecular dynamic simulations

    NASA Astrophysics Data System (ADS)

    Sebbari, Karim; Roques, Jérôme; Domain, Christophe; Simoni, Eric

    2012-10-01

    The behavior of the UO22+ uranyl ion at the water/NiO(100) interface was investigated for the first time using Born-Oppenheimer molecular dynamic simulations with the spin polarized DFT + U extension. A water/NiO(100) interface model was first optimized on a defect-free five layers slab thickness, proposed as a reliable surface model, with an explicit treatment of the solvent. Water molecules are adsorbed with a well-defined structure in a thickness of about 4 Å above the surface. The first layer, adsorbed on nickel atoms, remains mainly in molecular form but can partly dissociate at 293 K. Considering low acidic conditions, a bidentate uranyl ion complex was characterized on two surface oxygen species (arising from water molecules adsorption on nickel atoms) with d_{U{-O}_{adsorption}}= 2.39 Å. This complex is stable at 293 K due to iono-covalent bonds with an estimated charge transfer of 0.58 electron from the surface to the uranyl ion.

  4. Uranyl ion interaction at the water/NiO(100) interface: A predictive investigation by first-principles molecular dynamic simulations

    SciTech Connect

    Sebbari, Karim; Roques, Jerome; Simoni, Eric; Domain, Christophe

    2012-10-28

    The behavior of the UO{sub 2}{sup 2+} uranyl ion at the water/NiO(100) interface was investigated for the first time using Born-Oppenheimer molecular dynamic simulations with the spin polarized DFT +U extension. A water/NiO(100) interface model was first optimized on a defect-free five layers slab thickness, proposed as a reliable surface model, with an explicit treatment of the solvent. Water molecules are adsorbed with a well-defined structure in a thickness of about 4 A above the surface. The first layer, adsorbed on nickel atoms, remains mainly in molecular form but can partly dissociate at 293 K. Considering low acidic conditions, a bidentate uranyl ion complex was characterized on two surface oxygen species (arising from water molecules adsorption on nickel atoms) with d{sub U-O{sub a{sub d{sub s{sub o{sub r{sub p{sub t{sub i{sub o{sub n}}}}}}}}}}}=2.39 A. This complex is stable at 293 K due to iono-covalent bonds with an estimated charge transfer of 0.58 electron from the surface to the uranyl ion.

  5. A Spectroscopic Approach to Investigate the Molecular Interactions between the Newly Approved Irreversible ErbB blocker "Afatinib" and Bovine Serum Albumin

    PubMed Central

    2016-01-01

    The interaction of afatinib (AFB) with bovine serum albumin (BSA) was examined via fluorescence and UV-Vis spectroscopy. Spectrofluorimetric measurements revealed that AFB can strongly quench the BSA intrinsic fluorescence through producing a non-fluorescent complex. This quenching mechanism was thoroughly investigated with regard to the type of quenching, binding constant, number of binding locations and the fundamental thermodynamic parameters. Subsequently, the association constant of AFB with BSA was computed at three different temperatures and was found to range from 7.34 to 13.19 x105 L mol-1. Thermodynamic parameters calculations demonstrated a positive ΔSƟvalue with both negative ΔHϴand ΔGϴvalues for AFB–BSA complex, which in turn infers thata spontaneous binding is taking place with both electrostatic bonding and hydrophobic interactions participating in the binding of AFB and BSA. Similarly, the UV absorption spectra of AFB-BSA system were studied and confirmed the interaction. Conformational alteration of the protein upon binding to AFB was elaborated with the aid of three dimensional fluorescence measurements as well as synchronous fluorescence spectra. PMID:26751077

  6. A Spectroscopic Approach to Investigate the Molecular Interactions between the Newly Approved Irreversible ErbB blocker "Afatinib" and Bovine Serum Albumin.

    PubMed

    Alanazi, Amer M; Abdelhameed, Ali Saber

    2016-01-01

    The interaction of afatinib (AFB) with bovine serum albumin (BSA) was examined via fluorescence and UV-Vis spectroscopy. Spectrofluorimetric measurements revealed that AFB can strongly quench the BSA intrinsic fluorescence through producing a non-fluorescent complex. This quenching mechanism was thoroughly investigated with regard to the type of quenching, binding constant, number of binding locations and the fundamental thermodynamic parameters. Subsequently, the association constant of AFB with BSA was computed at three different temperatures and was found to range from 7.34 to 13.19 x10(5) L mol(-1). Thermodynamic parameters calculations demonstrated a positive ΔSƟ value with both negative ΔHϴ and ΔGϴ values for AFB-BSA complex, which in turn infers that a spontaneous binding is taking place with both electrostatic bonding and hydrophobic interactions participating in the binding of AFB and BSA. Similarly, the UV absorption spectra of AFB-BSA system were studied and confirmed the interaction. Conformational alteration of the protein upon binding to AFB was elaborated with the aid of three dimensional fluorescence measurements as well as synchronous fluorescence spectra. PMID:26751077

  7. Understanding polycaroboxylate interactions with counterions: A molecular modeling approach

    SciTech Connect

    Fitzwater, S.; Freeman, M.B.

    1993-12-31

    Low molecular weight polycarboyxlates, such as poly(acrylic acid), have utility as dispersants in a variety of commercial applications including home laundry detergents, mineral processing and water treatment. In general, counterions (Ca, Mg, Fe, etc.) are unavoidable in these applications and often dictate the polymer composition and molecular weight necessary for successful performance. The authors have been investigating the interaction of polycarboxylates with counterions in order to better understand how that interaction impacts on the dispersant properties of a polymer. Using computer modeling, it can be seen how molecular geometry, molecular dynamics, and the shape/polarity of the molecular surface are affected by counterion binding and polymer composition. The authors can then combine information from the modeling with experimental information and literature concepts to provide a direction toward the synthesis of improved low molecular weight polycarboxylate dispersants.

  8. Interactive association between biopolymers and biofunctions in carinata seeds as energy feedstock and their coproducts (carinata meal) from biofuel and bio-oil processing before and after biodegradation: current advanced molecular spectroscopic investigations.

    PubMed

    Yu, Peiqiang; Xin, Hangshu; Ban, Yajing; Zhang, Xuewei

    2014-05-01

    Recent advances in biofuel and bio-oil processing technology require huge supplies of energy feedstocks for processing. Very recently, new carinata seeds have been developed as energy feedstocks for biofuel and bio-oil production. The processing results in a large amount of coproducts, which are carinata meal. To date, there is no systematic study on interactive association between biopolymers and biofunctions in carinata seed as energy feedstocks for biofuel and bioethanol processing and their processing coproducts (carinata meal). Molecular spectroscopy with synchrotron and globar sources is a rapid and noninvasive analytical technique and is able to investigate molecular structure conformation in relation to biopolymer functions and bioavailability. However, to date, these techniques are seldom used in biofuel and bioethanol processing in other research laboratories. This paper aims to provide research progress and updates with molecular spectroscopy on the energy feedstock (carinata seed) and coproducts (carinata meal) from biofuel and bioethanol processing and show how to use these molecular techniques to study the interactive association between biopolymers and biofunctions in the energy feedstocks and their coproducts (carinata meal) from biofuel and bio-oil processing before and after biodegradation.

  9. Modelling refractive index changes due to molecular interactions

    NASA Astrophysics Data System (ADS)

    Varma, Manoj

    2016-03-01

    There are a large number of sensing techniques which use optical changes to monitor interactions between molecules. In the absence of fluorophores or other labels, the basic signal transduction mechanism relies on refractive index changes arising from the interactions of the molecules involved. A quantitative model incorporating molecular transport, reaction kinetics and optical mixing is presented which reveals important insights concerning the optimal detection of molecular interactions optically. Although conceptually simple, a comprehensive model such as this has not been reported anywhere. Specifically, we investigate the pros and cons of detecting molecular interactions in free solution relative to detecting molecular interactions on surfaces using surface bound receptor molecules such as antibodies. The model reveals that the refractive index change produced in surface based sensors is 2-3 orders of magnitude higher than that from interactions in free solution. On the other hand, the model also reveals that it is indeed possible to distinguish specific molecular interactions from non-specific ones based on free-solution bulk refractometry without any washing step necessary in surface based sensors. However, the refractive index change for free solution interactions predicted by the model is smaller than 10-7 RIU, even for large proteins such as IgG in sufficiently high concentrations. This value is smaller than the typical 10-6 RIU detection limit of most state of the art optical sensing techniques therefore requiring techniques with substantially higher index sensitivity such as Back Scattering Interferometry.

  10. Emerging molecular methods for male infertility investigation.

    PubMed

    Benkhalifa, Moncef; Montjean, Debbie; Belloc, Stephanie; Dalleac, Alain; Ducasse, Michel; Boyer, Pierre; Merviel, Philippe; Copin, Henri

    2014-01-01

    Male factors account for approximately 50% of reproductive pathology. Different disorders, including urogenital and endocrine system development abnormalities, lead to testicular and gametogenesis defects. Parallely, studies have reported that somatic and germ cell genome decay are a major cause of male infertility. It has been shown that in somatic karyotype, there is a higher incidence of chromosomal aberrations in infertile men than neonatal population and significant chromosome Y microdeletion or specific gene alterations in affected spermatogenesis. Karyotyping and FISH application at somatic and germ cell levels are no longer sufficient to investigate the potential contribution of genome disorders on male infertility. A wide range of molecular methods are required for better understanding of male infertility causes. Molecular omes and omics techniques have become a great tool to investigate male infertility from chromosome to protein. This review reports different molecular tests and methods that can be offered for male infertility investigation.

  11. Molecular interactions of quinidine with phospholipid bilayers.

    PubMed

    Suwalsky, M; Villena, F; Bagnara, M; Sotomayor, C P

    1995-01-01

    Quinidine (QUIN) is one of the most important and efficient antiarrhythmic drugs (AAD). It belongs to class I, which are the drugs that exert their action at the level of the sodium channels in the membrane of the myocard. Several hypotheses support the idea that the molecular mechanism of action of the AAD is via nonspecific interactions with phospholipids sited in the neighborhood of the channels. In order to probe the validity of these hypotheses, QUIN was made to interact with the phospholipids dimyristoylphosphadidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE). These interactions were performed in a hydrophobic and a hydrophilic medium under a wide range of molar ratios. The resulting products were analyzed by X-ray diffraction. QUIN solutions were also made to interact with DMPC liposomes, which were studied by fluorescent spectroscopy. Finally, human erythrocytes which were incubated with QUIN solutions were observed by scanning electron microscopy. The results of these experiments proved that QUIN indeed interacted with phospholipid bilayers. PMID:7546041

  12. Molecular beacons for protein-DNA interaction studies.

    PubMed

    Li, Jun; Cao, Zehui Charles; Tang, Zhiwen; Wang, Kemin; Tan, Weihong

    2008-01-01

    Real-time monitoring of DNA-protein interactions involving molecular beacon (MB) and molecular beacon aptamer (MBA) was discussed in this chapter. MBs are single-stranded oligonucleotide probes with a hairpin structure. MBs have been designed for oligonucleotide recognition and protein-DNA interaction studies. Real-time monitoring of enzymatic reactions, such as cleavage, ligation, and phosphorylation of single-stranded DNA by specific enzyme, has been studied using MBs. Meanwhile, a new generation of molecular probes, MBA, was designed by combining the excellent signal transduction properties of MBs with the specificity of aptamers for protein recognition. Two different aptamers, the one for thrombin and that for platelet-derived growth factor, have been successfully used to construct MBA probes. The interaction between the proteins and the MBA probes was investigated by fluorescence resonance energy transfer, fluorescence anisotropy, and time-resolved fluorescence. This chapter has reviewed our recent progress in this area.

  13. Teaching Noncovalent Interactions Using Protein Molecular Evolution

    ERIC Educational Resources Information Center

    Fornasari, Maria Silvina; Parisi, Gustavo; Echave, Julian

    2008-01-01

    Noncovalent interactions and physicochemical properties of amino acids are important topics in biochemistry courses. Here, we present a computational laboratory where the capacity of each of the 20 amino acids to maintain different noncovalent interactions are used to investigate the stabilizing forces in a set of proteins coming from organisms…

  14. Interactive investigations into planetary interiors

    NASA Astrophysics Data System (ADS)

    Rose, I.

    2015-12-01

    Many processes in Earth science are difficult to observe or visualize due to the large timescales and lengthscales over which they operate. The dynamics of planetary mantles are particularly challenging as we cannot even look at the rocks involved. As a result, much teaching material on mantle dynamics relies on static images and cartoons, many of which are decades old. Recent improvements in computing power and technology (largely driven by game and web development) have allowed for advances in real-time physics simulations and visualizations, but these have been slow to affect Earth science education.Here I demonstrate a teaching tool for mantle convection and seismology which solves the equations for conservation of mass, momentum, and energy in real time, allowing users make changes to the simulation and immediately see the effects. The user can ask and answer questions about what happens when they add heat in one place, or take it away from another place, or increase the temperature at the base of the mantle. They can also pause the simulation, and while it is paused, create and visualize seismic waves traveling through the mantle. These allow for investigations into and discussions about plate tectonics, earthquakes, hot spot volcanism, and planetary cooling.The simulation is rendered to the screen using OpenGL, and is cross-platform. It can be run as a native application for maximum performance, but it can also be embedded in a web browser for easy deployment and portability.

  15. Molecular interactions of graphene oxide with human blood plasma proteins

    NASA Astrophysics Data System (ADS)

    Kenry, Affa Affb Affc; Loh, Kian Ping; Lim, Chwee Teck

    2016-04-01

    We investigate the molecular interactions between graphene oxide (GO) and human blood plasma proteins. To gain an insight into the bio-physico-chemical activity of GO in biological and biomedical applications, we performed a series of biophysical assays to quantify the molecular interactions between GO with different lateral size distributions and the three essential human blood plasma proteins. We elucidate the various aspects of the GO-protein interactions, particularly, the adsorption, binding kinetics and equilibrium, and conformational stability, through determination of quantitative parameters, such as GO-protein association constants, binding cooperativity, and the binding-driven protein structural changes. We demonstrate that the molecular interactions between GO and plasma proteins are significantly dependent on the lateral size distribution and mean lateral sizes of the GO nanosheets and their subtle variations may markedly influence the GO-protein interactions. Consequently, we propose the existence of size-dependent molecular interactions between GO nanosheets and plasma proteins, and importantly, the presence of specific critical mean lateral sizes of GO nanosheets in achieving very high association and fluorescence quenching efficiency of the plasma proteins. We anticipate that this work will provide a basis for the design of graphene-based and other related nanomaterials for a plethora of biological and biomedical applications.

  16. Molecular signals in the interactions between plants and microbes.

    PubMed

    Clarke, H R; Leigh, J A; Douglas, C J

    1992-10-16

    The field of plant-microbe interactions has witnessed several recent breakthroughs, such as the molecular details of vir gene induction, identification of Nod factors, and the cloning and characterization of avr genes. Other breakthroughs, such as the cloning and characterization of R genes, appear imminent. Parallels to mammalian systems are emerging in the world of plant-microbe interactions, for example, ion channels formed by Rhizobium proteins, similarities of hrp genes to pathogenicity genes of mammalian pathogens, and plant signal transduction via calcium and protein phosphorylation. We remain, however, largely ignorant of many facets of signaling in plant-microbe interactions. We know little about how microbial signals are perceived by plants or how subsequent signal transduction occurs within plant cells and are probably unaware of many of the microbe-generated signals to which plants respond or of plant-generated signals to which bacteria and fungi respond. Contributions from those working on the genetics, molecular biology, and physiology of bacteria, fungi, and plants will be required to address these questions. The many nonpathogenic plant-microbe interactions in addition to the Rhizobium-plant interaction remain relatively unexplored. Genetic and molecular approaches are being initiated to investigate the signaling that is likely to underlie interactions such as those between mycorrhizal fungi and plant roots and between epiphytic bacteria and plant leaf surfaces. The importance of these interactions to plant growth and development makes it likely that they will figure more prominently at future symposia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1423587

  17. MOLECULAR INTERACTION POTENTIALS FOR THE DEVELOPMENT OF STRUCTURE-ACTIVITY RELATIONSHIPS

    EPA Science Inventory

    Abstract
    One reasonable approach to the analysis of the relationships between molecular structure and toxic activity is through the investigation of the forces and intermolecular interactions responsible for chemical toxicity. The interaction between the xenobiotic and the bio...

  18. Screened Electrostatic Interactions in Molecular Mechanics.

    PubMed

    Wang, Bo; Truhlar, Donald G

    2014-10-14

    In a typical application of molecular mechanics (MM), the electrostatic interactions are calculated from parametrized partial atomic charges treated as point charges interacting by radial Coulomb potentials. This does not usually yield accurate electrostatic interactions at van der Waals distances, but this is compensated by additional parametrized terms, for example Lennard-Jones potentials. In the present work, we present a scheme involving radial screened Coulomb potentials that reproduces the accurate electrostatics much more accurately. The screening accounts for charge penetration of one subsystem's charge cloud into that of another subsystem, and it is incorporated into the interaction potential in a way similar to what we proposed in a previous article (J. Chem. Theory Comput. 2010, 6, 3330) for combined quantum mechanical and molecular mechanical (QM/MM) simulations, but the screening parameters are reoptimized for MM. The optimization is carried out with electrostatic-potential-fitted partial atomic charges, but the optimized parameters should be useful with any realistic charge model. In the model we employ, the charge density of an atom is approximated as the sum of a point charge representing the nucleus and inner electrons and a smeared charge representing the outermost electrons; in particular, for all atoms except hydrogens, the smeared charge represents the two outermost electrons in the present model. We find that the charge penetration effect can cause very significant deviations from the popular point-charge model, and by comparison to electrostatic interactions calculated by symmetry-adapted perturbation theory, we find that the present results are considerably more accurate than point-charge electrostatic interactions. The mean unsigned error in electrostatics for a large and diverse data set (192 interaction energies) decreases from 9.2 to 3.3 kcal/mol, and the error in the electrostatics for 10 water dimers decreases from 1.7 to 0.5 kcal

  19. Screened Electrostatic Interactions in Molecular Mechanics.

    PubMed

    Wang, Bo; Truhlar, Donald G

    2014-10-14

    In a typical application of molecular mechanics (MM), the electrostatic interactions are calculated from parametrized partial atomic charges treated as point charges interacting by radial Coulomb potentials. This does not usually yield accurate electrostatic interactions at van der Waals distances, but this is compensated by additional parametrized terms, for example Lennard-Jones potentials. In the present work, we present a scheme involving radial screened Coulomb potentials that reproduces the accurate electrostatics much more accurately. The screening accounts for charge penetration of one subsystem's charge cloud into that of another subsystem, and it is incorporated into the interaction potential in a way similar to what we proposed in a previous article (J. Chem. Theory Comput. 2010, 6, 3330) for combined quantum mechanical and molecular mechanical (QM/MM) simulations, but the screening parameters are reoptimized for MM. The optimization is carried out with electrostatic-potential-fitted partial atomic charges, but the optimized parameters should be useful with any realistic charge model. In the model we employ, the charge density of an atom is approximated as the sum of a point charge representing the nucleus and inner electrons and a smeared charge representing the outermost electrons; in particular, for all atoms except hydrogens, the smeared charge represents the two outermost electrons in the present model. We find that the charge penetration effect can cause very significant deviations from the popular point-charge model, and by comparison to electrostatic interactions calculated by symmetry-adapted perturbation theory, we find that the present results are considerably more accurate than point-charge electrostatic interactions. The mean unsigned error in electrostatics for a large and diverse data set (192 interaction energies) decreases from 9.2 to 3.3 kcal/mol, and the error in the electrostatics for 10 water dimers decreases from 1.7 to 0.5 kcal

  20. Molecular interactions of flavonoids to pepsin: Insights from spectroscopic and molecular docking studies.

    PubMed

    Zeng, Hua-Jin; Yang, Ran; Liang, Huili; Qu, Ling-Bo

    2015-01-01

    In the work described on this paper, the inhibitory effect of 10 flavonoids on pepsin and the interactions between them were investigated by a combination of spectroscopic and molecular docking methods. The results indicated that all flavonoids could bind with pepsin to form flavonoid-pepsin complexes. The binding parameters obtained from the data at different temperatures revealed that flavonoids could spontaneously interact with pepsin mainly through electrostatic forces and hydrophobic interactions with one binding site. According to synchronous and three-dimensional fluorescence spectra and molecular docking results, all flavonoids bound directly into the enzyme cavity site and the binding influenced the microenvironment and conformation of the pepsin activity site which resulted in the reduced enzyme activity. The present study provides direct evidence at a molecular level to understand the mechanism of digestion caused by flavonoids.

  1. Controlling single-molecule junction conductance by molecular interactions

    PubMed Central

    Kitaguchi, Y.; Habuka, S.; Okuyama, H.; Hatta, S.; Aruga, T.; Frederiksen, T.; Paulsson, M.; Ueba, H.

    2015-01-01

    For the rational design of single-molecular electronic devices, it is essential to understand environmental effects on the electronic properties of a working molecule. Here we investigate the impact of molecular interactions on the single-molecule conductance by accurately positioning individual molecules on the electrode. To achieve reproducible and precise conductivity measurements, we utilize relatively weak π-bonding between a phenoxy molecule and a STM-tip to form and cleave one contact to the molecule. The anchoring to the other electrode is kept stable using a chalcogen atom with strong bonding to a Cu(110) substrate. These non-destructive measurements permit us to investigate the variation in single-molecule conductance under different but controlled environmental conditions. Combined with density functional theory calculations, we clarify the role of the electrostatic field in the environmental effect that influences the molecular level alignment. PMID:26135251

  2. Controlling single-molecule junction conductance by molecular interactions

    NASA Astrophysics Data System (ADS)

    Kitaguchi, Y.; Habuka, S.; Okuyama, H.; Hatta, S.; Aruga, T.; Frederiksen, T.; Paulsson, M.; Ueba, H.

    2015-07-01

    For the rational design of single-molecular electronic devices, it is essential to understand environmental effects on the electronic properties of a working molecule. Here we investigate the impact of molecular interactions on the single-molecule conductance by accurately positioning individual molecules on the electrode. To achieve reproducible and precise conductivity measurements, we utilize relatively weak π-bonding between a phenoxy molecule and a STM-tip to form and cleave one contact to the molecule. The anchoring to the other electrode is kept stable using a chalcogen atom with strong bonding to a Cu(110) substrate. These non-destructive measurements permit us to investigate the variation in single-molecule conductance under different but controlled environmental conditions. Combined with density functional theory calculations, we clarify the role of the electrostatic field in the environmental effect that influences the molecular level alignment.

  3. 2010 Atomic & Molecular Interactions Gordon Research Conference

    SciTech Connect

    Todd Martinez

    2010-07-23

    The Atomic and Molecular Interactions Gordon Conferences is justifiably recognized for its broad scope, touching on areas ranging from fundamental gas phase and gas-condensed matter collision dynamics, to laser-molecule interactions, photophysics, and unimolecular decay processes. The meeting has traditionally involved scientists engaged in fundamental research in gas and condensed phases and those who apply these concepts to systems of practical chemical and physical interest. A key tradition in this meeting is the strong mixing of theory and experiment throughout. The program for 2010 conference continues these traditions. At the 2010 AMI GRC, there will be talks in 5 broadly defined and partially overlapping areas of intermolecular interactions and chemical dynamics: (1) Photoionization and Photoelectron Dynamics; (2) Quantum Control and Molecules in Strong Fields; (3) Photochemical Dynamics; (4) Complex Molecules and Condensed Phases; and (5) Clusters and Reaction Dynamics. These areas encompass many of the most productive and exciting areas of chemical physics, including both reactive and nonreactive processes, intermolecular and intramolecular energy transfer, and photodissociation and unimolecular processes. Gas phase dynamics, van der Waals and cluster studies, laser-matter interactions and multiple potential energy surface phenomena will all be discussed.

  4. Quantum Theory of Atomic and Molecular Structures and Interactions

    NASA Astrophysics Data System (ADS)

    Makrides, Constantinos

    This dissertation consists of topics in two related areas of research that together provide quantum mechanical descriptions of atomic and molecular interactions and reactions. The first is the ab initio electronic structure calculation that provides the atomic and molecular interaction potential, including the long-range potential. The second is the quantum theory of interactions that uses such potentials to understand scattering, long-range molecules, and reactions. In ab initio electronic structure calculations, we present results of dynamic polarizabilities for a variety of atoms and molecules, and the long-range dispersion coefficients for a number of atom-atom and atom-molecule cases. We also present results of a potential energy surface for the triatomic lithium-ytterbium-lithium system, aimed at understanding the related chemical reactions. In the quantum theory of interactions, we present a multichannel quantum-defect theory (MQDT) for atomic interactions in a magnetic field. This subject, which is complex especially for atoms with hyperfine structure, is essential for the understanding and the realization of control and tuning of atomic interactions by a magnetic field: a key feature that has popularized cold atom physics in its investigations of few-body and many-body quantum systems. Through the example of LiK, we show how MQDT provides a systematic and an efficient understanding of atomic interaction in a magnetic field, especially magnetic Feshbach resonances in nonzero partial waves.

  5. Thermodynamic molecular switch in macromolecular interactions.

    PubMed

    Chun, P W

    2000-01-01

    It is known that most living systems can live and operate optimally only at a sharply defined temperature, or over a limited temperature range, at best, which implies that many basic biochemical interactions exhibit a well-defined Gibbs free energy minimum as a function of temperature. The Gibbs free energy change, deltaG(o) (T), for biological systems shows a complicated behavior, in which deltaG(o)(T) changes from positive to negative, then reaches a negative value of maximum magnitude (favorable), and finally becomes positive as temperature increases. The critical factor in this complicated thermodynamic behavior is a temperature-dependent heat capacity change (deltaCp(o)(T) of reaction, which is positive at low temperature, but switches to a negative value at a temperature well below the ambient range. Thus, the thermodynamic molecular switch determines the behavior patterns of the Gibbs free energy change, and hence a change in the equilibrium constant, Keq, and/or spontaneity. The subsequent, mathematically predictable changes in deltaH(o)(T), deltaS(o)(T), deltaW(o)(T), and deltaG(o)(T) give rise to the classically observed behavior patterns in biological reactivity, as demonstrated in three interacting protein systems: the acid dimerization reaction of alpha-chymotrypsin at low pH, interaction of chromogranin A with the intraluminal loop peptide of the inositol 1,4,5-triphosphate receptor at pH 5.5, and the binding of L-arabinose and D-galactose to the L-arabinose binding protein of Escherichia coli. In cases of protein unfolding of four mutants of phage T4 lysozyme, no thermodynamic molecular switch is observed.

  6. The JPL Molecular Contamination Investigation Facility

    NASA Technical Reports Server (NTRS)

    Taylor, Daniel M.; Soules, David; Osborn, David

    1990-01-01

    The Molecular Contamination Investigation Facility (MCIF) is discussed in terms of its use for improving the far-UV performance of a camera and its broader applications. The MCIF incorporates two independent vacuum systems with sample isolation chambers and regulated heat exchangers as well as three quartz-crystal microbalances (QCMs) and a residual gas analyzer. One cryogenic QCM is heat sunk into an LN2 heat exchanger, while the others are thermoelectrically controlled and are heat sunk into a regulated heat exchanger. Outgas accumulation can be measured at three surface temperatures between -180 and 80 C simultaneously, and results are presented for the testing of 34 samples in a large-chambered system and 22 samples in a system with a smaller chamber. The MCIF results provide a database for fabrication processes, material selection, maximum bakeout temperatures, and the development of an ultraclean bakeout chamber.

  7. Nanoscale swimmers: hydrodynamic interactions and propulsion of molecular machines

    NASA Astrophysics Data System (ADS)

    Sakaue, T.; Kapral, R.; Mikhailov, A. S.

    2010-06-01

    Molecular machines execute nearly regular cyclic conformational changes as a result of ligand binding and product release. This cyclic conformational dynamics is generally non-reciprocal so that under time reversal a different sequence of machine conformations is visited. Since such changes occur in a solvent, coupling to solvent hydrodynamic modes will generally result in self-propulsion of the molecular machine. These effects are investigated for a class of coarse grained models of protein machines consisting of a set of beads interacting through pair-wise additive potentials. Hydrodynamic effects are incorporated through a configuration-dependent mobility tensor, and expressions for the propulsion linear and angular velocities, as well as the stall force, are obtained. In the limit where conformational changes are small so that linear response theory is applicable, it is shown that propulsion is exponentially small; thus, propulsion is nonlinear phenomenon. The results are illustrated by computations on a simple model molecular machine.

  8. Investigation of drug interactions with pinaverium bromide.

    PubMed

    Devred, C; Godeau, P; Guerot, C; Librez, P; Mougeot, G; Orsetti, A; Segrestaa, J M

    1986-01-01

    A series of studies was carried out at 6 centres to investigate possible drug interaction between the spasmolytic, pinaverium bromide, and cardiac glycosides, anticoagulants and hypoglycaemic agents given to patients as part of the long-term treatment of their condition. The results of clinical and laboratory investigations did not show any evidence of pinaverium bromide interfering with the action or activity of any of the drugs studied. PMID:3084176

  9. Molecular dynamics simulations on the interactions of low molecular weight natural organic acids with C60.

    PubMed

    Sun, Qian; Xie, Hong-Bin; Chen, Jingwen; Li, Xuehua; Wang, Zhuang; Sheng, Lianxi

    2013-07-01

    As an important part of dissolved organic matter (DOM), low molecular weight organic acids (LOAs) may play a key role in the process for DOM stabilizing carbon nanomaterials (e.g. C60) suspensions in aquatic environment. In addition, both LOAs and C60 have been detected in the troposphere and therefore have a chance to interact with each other in the gaseous phase. However, the mechanism for LOAs-C60 interactions and their environmental implications need further investigations. In this study, molecular dynamics (MD) simulation was employed to investigate the interactions between both neutral and ionic LOAs with C60 in vacuum and water. The results showed that the adsorptions of all LOAs on C60 in energy are favorable, and the aromatic acids have stronger interactions with C60 than the aliphatic acids in vacuum and water. The interaction energies (Eint) of the LOA anions with C60 were weaker than those of their corresponding neutral LOA molecules. The models were also developed to predict and interpret Eint based on the results from MD simulations. Dispersion, induction and hydrophobic interactions were found to be the dominating factor in Eint. These findings indicate that cost-efficient MD simulation can be employed as an important tool to predict the adsorption behavior of LOAs on carbon nanomaterials.

  10. Break-junctions for investigating transport at the molecular scale

    NASA Astrophysics Data System (ADS)

    Schwarz, Florian; Lörtscher, Emanuel

    2014-11-01

    Break-junctions (BJs) enable a pair of atomic-sized electrodes to be created and the relative position between them to be controlled with sub-nanometer accuracy by mechanical means—a level of microscopic control that is not yet achievable by top-down fabrication. Locally, a BJ consists of a single-atom contact, an arrangement that is ideal not only to study various types of quantum point contacts, but also to investigate transport through an individual molecule that can bridge such a junction. In this topical review, we will provide a broad overview on the field of single-molecule electronics, in which BJs serve as the main tool of investigation. To correlate the molecular structure and transport properties to gain a fundamental understanding of the underlying transport mechanisms at the molecular scale, basic experiments that systematically cover all aspects of transport by rational chemical design and tailored experiments are needed. The variety of fascinating transport mechanisms and intrinsic molecular functionalities discovered in the past range from nonlinear transport over conductance switching to quantum interference effects observable even at room temperature. Beside discussing these results, we also look at novel directions and the most recent advances in molecular electronics investigating simultaneously electronic transport and also the mechanical and thermal properties of single-molecule junctions as well as the interaction between molecules and light. Finally, we will describe the requirements for a stepwise transition from fundamental BJ experiments towards technology-relevant architectures for future nanoelectronics applications based on ultimately-scaled molecular building blocks.

  11. Molecular interactions with ice: Molecular embedding, adsorption, detection, and release

    SciTech Connect

    Gibson, K. D.; Langlois, Grant G.; Li, Wenxin; Sibener, S. J.; Killelea, Daniel R.

    2014-11-14

    The interaction of atomic and molecular species with water and ice is of fundamental importance for chemistry. In a previous series of publications, we demonstrated that translational energy activates the embedding of Xe and Kr atoms in the near surface region of ice surfaces. In this paper, we show that inert molecular species may be absorbed in a similar fashion. We also revisit Xe embedding, and further probe the nature of the absorption into the selvedge. CF{sub 4} molecules with high translational energies (≥3 eV) were observed to embed in amorphous solid water. Just as with Xe, the initial adsorption rate is strongly activated by translational energy, but the CF{sub 4} embedding probability is much less than for Xe. In addition, a larger molecule, SF{sub 6}, did not embed at the same translational energies that both CF{sub 4} and Xe embedded. The embedding rate for a given energy thus goes in the order Xe > CF{sub 4} > SF{sub 6}. We do not have as much data for Kr, but it appears to have a rate that is between that of Xe and CF{sub 4}. Tentatively, this order suggests that for Xe and CF{sub 4}, which have similar van der Waals radii, the momentum is the key factor in determining whether the incident atom or molecule can penetrate deeply enough below the surface to embed. The more massive SF{sub 6} molecule also has a larger van der Waals radius, which appears to prevent it from stably embedding in the selvedge. We also determined that the maximum depth of embedding is less than the equivalent of four layers of hexagonal ice, while some of the atoms just below the ice surface can escape before ice desorption begins. These results show that energetic ballistic embedding in ice is a general phenomenon, and represents a significant new channel by which incident species can be trapped under conditions where they would otherwise not be bound stably as surface adsorbates. These findings have implications for many fields including environmental science, trace gas

  12. Monitoring molecular beacon/DNA interactions using atomic force microscopy.

    PubMed

    Jin, Yan; Wang, Kemin; Tan, Weihong; Wu, Ping; Wang, Qing; Huang, Hongmei; Huang, Shasheng; Tang, Zhiwen; Guo, Qiuping

    2004-10-01

    The molecular beacon (MB) is a new fluorescence probe containing a single-stranded oligonucleotide with a probe sequence embedded in complementary sequences that form a hairpin stem. Due to the inherent fluorescent signal transduction mechanism, an MB functions as a sensitive probe with a high signal-to-background ratio for real-time monitoring and provides a variety of exciting opportunities in DNA, RNA, and protein studies. To better understand the properties of MBs, the specific interactions between MB and target DNA (complementary and one-base mismatch) have been directly investigated by atomic force microscopy. The interaction force between a linear DNA probe and the target DNA was also detected and compared to that between MB and target DNA. The results demonstrate the high specificity of the MB/target DNA compared to the linear DNA/target DNA interaction.

  13. Molecular Indicators of Soil Humification and Interaction with Heavy Metals

    SciTech Connect

    Fan, Teresa W.-M.; Higashi, Richard M.; Cassel, Teresa; Green, Peter; Lane, Andrew N.

    2003-03-26

    For stabilization of heavy metals at contaminated sites, interaction of soil organic matter (SOM) with heavy metal ions is critically important for long-term sustainability, a factor that is poorly understood at the molecular level. Using 13C- and 15N-labeled soil humates (HS), we investigated the turnover of five organic amendments (celluose, wheat straw, pine shavings, chitin and bone meal) in relation to heavy metal ion leaching in soil column experiments. The labeled molecular substructures in HS were examined by multinuclear 2-D NMR and pyrolysis GC-MS while the element profile in the leachates was analyzed by ICP-MS. Preliminary analysis revealed that peptidic and polysaccharidic structures were highly enriched, which suggests their microbial origin. Cd(II) leaching was significantly attenuated with humification of lignocellulosic materials. Correlation of 13C and 15N turnovers of HS substructures to metal leaching is underway.

  14. Hepatitis A virus: host interactions, molecular epidemiology and evolution.

    PubMed

    Vaughan, Gilberto; Goncalves Rossi, Livia Maria; Forbi, Joseph C; de Paula, Vanessa S; Purdy, Michael A; Xia, Guoliang; Khudyakov, Yury E

    2014-01-01

    Infection with hepatitis A virus (HAV) is the commonest viral cause of liver disease and presents an important public health problem worldwide. Several unique HAV properties and molecular mechanisms of its interaction with host were recently discovered and should aid in clarifying the pathogenesis of hepatitis A. Genetic characterization of HAV strains have resulted in the identification of different genotypes and subtypes, which exhibit a characteristic worldwide distribution. Shifts in HAV endemicity occurring in different parts of the world, introduction of genetically diverse strains from geographically distant regions, genotype displacement observed in some countries and population expansion detected in the last decades of the 20th century using phylogenetic analysis are important factors contributing to the complex dynamics of HAV infections worldwide. Strong selection pressures, some of which, like usage of deoptimized codons, are unique to HAV, limit genetic variability of the virus. Analysis of subgenomic regions has been proven useful for outbreak investigations. However, sharing short sequences among epidemiologically unrelated strains indicates that specific identification of HAV strains for molecular surveillance can be achieved only using whole-genome sequences. Here, we present up-to-date information on the HAV molecular epidemiology and evolution, and highlight the most relevant features of the HAV-host interactions.

  15. Drug Interactions with New and Investigational Antiretrovirals

    PubMed Central

    Brown, Kevin C.; Paul, Sunita; Kashuba, Angela D.M.

    2010-01-01

    More than 20 individual and fixed-dose combinations of antiretrovirals are approved for the treatment of human immunodeficiency virus (HIV) infection. However, owing to the ongoing limitations of drug resistance and adverse effects, new treatment options are still required. A number of promising new agents in existing or new drug classes are in development or have recently been approved by the US FDA. Since these agents will be used in combination with other new and existing antiretrovirals, understanding the potential for drug interactions between these compounds is critical to their appropriate use. This article summarizes the drug interaction potential of new and investigational protease inhibitors (darunavir), non-nucleoside reverse transcriptase inhibitors (etravirine and rilpivirine), chemokine receptor antagonists (maraviroc, vicriviroc and INCB 9471), integrase inhibitors (raltegravir and elvitegravir) and maturation inhibitors (bevirimat). PMID:19492868

  16. The MIntAct Project and Molecular Interaction Databases.

    PubMed

    Licata, Luana; Orchard, Sandra

    2016-01-01

    Molecular interaction databases collect, organize, and enable the analysis of the increasing amounts of molecular interaction data being produced and published as we move towards a more complete understanding of the interactomes of key model organisms. The organization of these data in a structured format supports analyses such as the modeling of pairwise relationships between interactors into interaction networks and is a powerful tool for understanding the complex molecular machinery of the cell. This chapter gives an overview of the principal molecular interaction databases, in particular the IMEx databases, and their curation policies, use of standardized data formats and quality control rules. Special attention is given to the MIntAct project, in which IntAct and MINT joined forces to create a single resource to improve curation and software development efforts. This is exemplified as a model for the future of molecular interaction data collation and dissemination. PMID:27115627

  17. Battle and Ballet: Molecular Interactions between the Sexes in Drosophila

    PubMed Central

    2009-01-01

    Varied and fascinating interactions occur between males and females to lead to the production of progeny. Interactions between the sexes continue even after the act of mating—but at the molecular and cellular level instead of between individual animals. Molecules transferred from males to females during mating (via the seminal fluid) exert potent effects on females’ physiology and (at least in some animals) on behavior. Taking advantage of genetic, genomic, and biochemical tools for Drosophila, we investigate molecular interactions that underlie this form of chemical communication. Recent data show that molecules and cells from both sexes participate in this “ballet,” facilitating the mutually beneficial outcome of increased progeny production. Examples to be presented include the storage and utilization of sperm in the mated female, and a proteolytic pathway that begins in the male but ends in the female and involves both male and female contributions. Despite the joint benefit of increased progeny production, the “interests” of the mating male can differ from those of his mate. Over evolutionary time this disconnect can, in theory, precipitate a “battle” between the sexes, potentially leading to the rapid sequence changes that have been observed for some seminal proteins across species. PMID:19349638

  18. Using molecular beacons to probe molecular interactions between lactate dehydrogenase and single-stranded DNA.

    PubMed

    Fang, X; Li, J J; Tan, W

    2000-07-15

    The interactions between two key macromolecular species, nucleic acids and proteins, control many important biological processes. There have been limited effective methodologies to study these interactions in real time. In this work, we have applied a newly developed molecular beacon (MB) DNA probe for the analysis of an enzyme, lactate dehydrogenase (LDH), and for the investigation of its properties of binding with single-stranded DNA. Molecular beacons are single-stranded oligonucleotide probes designed to report the presence of specific complementary nucleic acids by fluorescence detection. The interaction between LDH and MB has resulted in a significant fluorescence signal enhancement, which is used for the elucidation of MB/LDH binding properties. The processes of binding between MB and different isoenzymes of LDH have been studied. The results show that the stoichiometry of LDH-5/MB binding is 1:1, and the binding constant is 1.9 x 10(-7) M(-1). We have also studied salt effects, binding sites, temperature effects, pH effects, and the binding specificities for different isoenzymes. Our results demonstrate that MB can be effectively used for sensitive protein quantitation and for efficient protein-DNA interaction studies. MB has a signal transduction mechanism built within the molecule and can thus be used for the development of rapid protein assays and for real-time measurements.

  19. Molecular crime scene investigation - dusting for fingerprints.

    PubMed

    Jürgen Bajorath

    2013-12-01

    In chemoinformatics and drug design, fingerprints (FPs) are defined as string representations of molecular structure and properties and are popular descriptors for similarity searching. FPs are generally characterized by the simplicity of their design and ease of use. Despite a long history in chemoinformatics, the potential and limitations of FP searching are often not well under- stood. Standard FPs can also be subjected to engineering techniques to tune them for specific search applications.

  20. Molecular investigations of flaxseed mucilage polysaccharides.

    PubMed

    Roulard, Romain; Petit, Emmanuel; Mesnard, François; Rhazi, Larbi

    2016-05-01

    The molecular properties of flaxseed mucilage were determined using a multi-angle laser light scattering (MALLS) detector coupled on-line to size exclusion chromatography (SEC) and asymmetric flow field-flow fractionation (AF4). Water and salt solution were tested as mobile phases. The SEC-MALLS method gave partial information and enabled molecular characterization of disaggregated mucilage molecules. Regardless of the eluent used, the observed Mw ranged from about 1.6 × 10(6) to more than 10 × 10(6) g/mol for mucilage polysaccharides. The AF4-MALLS system enabled a complete analysis of mucilage carbohydrate aggregates in water, in which two populations were satisfactorily separated. The molecular weight distribution (MWD) of molecules ranged from 1.5 × 10(6) to more than 4 × 10(8) g/mol. Experiments showed that the conformational structure of mucilage molecules was strongly influenced by ionic strength. Mucilage carbohydrates exhibited a spherical and compact structure in NaCl solution while they displayed a random-coil conformation in water. PMID:26851358

  1. Molecular investigations of flaxseed mucilage polysaccharides.

    PubMed

    Roulard, Romain; Petit, Emmanuel; Mesnard, François; Rhazi, Larbi

    2016-05-01

    The molecular properties of flaxseed mucilage were determined using a multi-angle laser light scattering (MALLS) detector coupled on-line to size exclusion chromatography (SEC) and asymmetric flow field-flow fractionation (AF4). Water and salt solution were tested as mobile phases. The SEC-MALLS method gave partial information and enabled molecular characterization of disaggregated mucilage molecules. Regardless of the eluent used, the observed Mw ranged from about 1.6 × 10(6) to more than 10 × 10(6) g/mol for mucilage polysaccharides. The AF4-MALLS system enabled a complete analysis of mucilage carbohydrate aggregates in water, in which two populations were satisfactorily separated. The molecular weight distribution (MWD) of molecules ranged from 1.5 × 10(6) to more than 4 × 10(8) g/mol. Experiments showed that the conformational structure of mucilage molecules was strongly influenced by ionic strength. Mucilage carbohydrates exhibited a spherical and compact structure in NaCl solution while they displayed a random-coil conformation in water.

  2. VISUALIZATION OF MOLECULAR INTERACTIONS BY FLUORESCENCE COMPLEMENTATION

    PubMed Central

    Kerppola, Tom K.

    2008-01-01

    The visualization of protein complexes in living cells enables validation of protein interactions in their normal environment and determination of their subcellular localization. The bimolecular fluorescence complementation (BiFC) assay has been used to visualize interactions among multiple proteins in many cell types and organisms. This assay is based on the association between two fluorescent-protein fragments when they are brought together by an interaction between proteins fused to the fragments. Modified forms of this assay have been used to visualize the competition between alternative interaction partners and the covalent modification of proteins by ubiquitin family peptides. PMID:16625152

  3. Molecular Statics Simulation of Hydrogen Defect Interaction in Tungsten

    NASA Astrophysics Data System (ADS)

    Li, Xiaochun; Liu, Yinan; Yu, Yi; Niu, Guojian; Luo, Guangnan; Shu, Xiaolin

    2015-06-01

    Hydrogen (H) defect interactions have been investigated by molecular statics simulations in tungsten (W), including H-H interactions and interactions between H and W self-interstitial atoms. The interactions between H and small H-vacancy clusters are also demonstrated; the binding energies of an H, a vacancy and a self-interstitial W to an H-vacancy cluster depend on the H-to-vacancy ratio. We conclude that H bubble formation needs a high concentration of H in W for the H bubble nucleation and growth, which are also governed by the H-to-vacancy ratio of the cluster. The vacancy first combines with H atoms and a cluster forms, then the H-vacancy cluster goes through the whole process of vacancy capture, H capture, and vacancy capture again, and as a result the H-vacancy cluster grows larger and larger. Finally, the H bubble forms. supported by National Natural Science Foundation of China (Nos. 51171008 and 11405201) and the National Magnetic Confinement Fusion Science Program of China (No. 2013GB1090)

  4. STALK : an interactive virtual molecular docking system.

    SciTech Connect

    Levine, D.; Facello, M.; Hallstrom, P.; Reeder, G.; Walenz, B.; Stevens, F.; Univ. of Illinois

    1997-04-01

    Several recent technologies-genetic algorithms, parallel and distributed computing, virtual reality, and high-speed networking-underlie a new approach to the computational study of how biomolecules interact or 'dock' together. With the Stalk system, a user in a virtual reality environment can interact with a genetic algorithm running on a parallel computer to help in the search for likely geometric configurations.

  5. Detailed Investigations of Interactions between Ionizing Radiation and Neutral Gases

    SciTech Connect

    Landers, Allen L

    2014-03-31

    We are investigating phenomena that stem from the many body dynamics associated with ionization of an atom or molecule by photon or charged particle. Our program is funded through the Department of Energy EPSCoR Laboratory Partnership Award in collaboration with Lawrence Berkeley National Laboratory. We are using variations on the well established COLTRIMS technique to measure ions and electrons ejected during these interactions. Photoionization measurements take place at the Advanced Light Source at LBNL as part of the ALS-COLTRIMS collaboration with the groups of Reinhard Dörner at Frankfurt and Ali Belkacem at LBNL. Additional experiments on charged particle impact are conducted locally at Auburn University where we are studying the dissociative molecular dynamics following interactions with either ions or electrons over a velocity range of 1 to 12 atomic units.

  6. Experimental investigation of vortex-fin interaction

    NASA Technical Reports Server (NTRS)

    Washburn, Anthony E.; Jenkins, Luther N.; Ferman, Marty A.

    1993-01-01

    An experimental investigation has been conducted to examine the mechanisms of vortex-fin interaction on a twin-fin configuration. The investigation included a parametric study of the effect of tail location. The vortices were generated by a 76 deg sharp-edged delta wing with vertical tails mounted behind the wing. The model included both a dynamically-scaled flexible tail and a pressure instrumented rigid tail. Surface oil-flow patterns, off-body laser light sheet visualizations, aerodynamic load measurements, mean and unsteady flexible tail response, and unsteady tail surface pressure measurements were obtained. The results show that the tail location did not affect the upstream trajectory of the delta wing vortex. The tail location did affect the location of vortex breakdown, the global structure of the flow field, the aerodynamic loads, and the fin buffeting levels. The buffeting levels were reduced as the fins were moved laterally toward the vortex core trajectory. Two distinct peaks were observed in the pressure excitation spectra in the post-breakdown flow. Finally, the presence of the flexible tail opposite the rigid pressure tail altered the pressure measurements at one angle of attack.

  7. Molecular microenvironments: Solvent interactions with nucleic acid bases and ions

    NASA Technical Reports Server (NTRS)

    Macelroy, R. D.; Pohorille, A.

    1986-01-01

    The possibility of reconstructing plausible sequences of events in prebiotic molecular evolution is limited by the lack of fossil remains. However, with hindsight, one goal of molecular evolution was obvious: the development of molecular systems that became constituents of living systems. By understanding the interactions among molecules that are likely to have been present in the prebiotic environment, and that could have served as components in protobiotic molecular systems, plausible evolutionary sequences can be suggested. When stable aggregations of molecules form, a net decrease in free energy is observed in the system. Such changes occur when solvent molecules interact among themselves, as well as when they interact with organic species. A significant decrease in free energy, in systems of solvent and organic molecules, is due to entropy changes in the solvent. Entropy-driven interactioins played a major role in the organization of prebiotic systems, and understanding the energetics of them is essential to understanding molecular evolution.

  8. Interactive analysis of systems biology molecular expression data

    PubMed Central

    Zhang, Mingwu; Ouyang, Qi; Stephenson, Alan; Kane, Michael D; Salt, David E; Prabhakar, Sunil; Burgner, John; Buck, Charles; Zhang, Xiang

    2008-01-01

    Background Systems biology aims to understand biological systems on a comprehensive scale, such that the components that make up the whole are connected to one another and work through dependent interactions. Molecular correlations and comparative studies of molecular expression are crucial to establishing interdependent connections in systems biology. The existing software packages provide limited data mining capability. The user must first generate visualization data with a preferred data mining algorithm and then upload the resulting data into the visualization package for graphic visualization of molecular relations. Results Presented is a novel interactive visual data mining application, SysNet that provides an interactive environment for the analysis of high data volume molecular expression information of most any type from biological systems. It integrates interactive graphic visualization and statistical data mining into a single package. SysNet interactively presents intermolecular correlation information with circular and heatmap layouts. It is also applicable to comparative analysis of molecular expression data, such as time course data. Conclusion The SysNet program has been utilized to analyze elemental profile changes in response to an increasing concentration of iron (Fe) in growth media (an ionomics dataset). This study case demonstrates that the SysNet software is an effective platform for interactive analysis of molecular expression information in systems biology. PMID:18312669

  9. Interaction of methotrexate with trypsin analyzed by spectroscopic and molecular modeling methods

    NASA Astrophysics Data System (ADS)

    Wang, Yanqing; Zhang, Hongmei; Cao, Jian; Zhou, Qiuhua

    2013-11-01

    Trypsin is one of important digestive enzymes that have intimate correlation with human health and illness. In this work, the interaction of trypsin with methotrexate was investigated by spectroscopic and molecular modeling methods. The results revealed that methotrexate could interact with trypsin with about one binding site. Methotrexate molecule could enter into the primary substrate-binding pocket, resulting in inhibition of trypsin activity. Furthermore, the thermodynamic analysis implied that electrostatic force, hydrogen bonding, van der Waals and hydrophobic interactions were the main interactions for stabilizing the trypsin-methotrexate system, which agreed well with the results from the molecular modeling study.

  10. Characteristics of Quasi-Molecular State Interaction

    SciTech Connect

    Devdariani, A.; Dalimier, E.; Kereselidze, T.; Noselidze, I.; Rebentrost, F.; Sauvan, P.

    2008-10-22

    The quasi-molecular dipole transition moments have been considered analytically within the framework of the two-state approximation with particular emphasis on their roots (zeros) on spectral manifestations of the roots in the adiabatic diabatic limits. The interrelation between the spectral features the non-adiabatic transitions found in [1] has been demonstrated for excited state charge exchange Al{sup +12}(n = 4)+C{sup +6}{yields}Al{sup +13}+C{sup +5}(n = 2)

  11. Molecular Dynamics of Shock Wave Interaction with Nanoscale Structured Materials

    NASA Astrophysics Data System (ADS)

    Al-Qananwah, Ahmad K.

    Typical theoretical treatments of shock wave interactions are based on a continuum approach, which cannot resolve the spatial variations in solids with nano-scale porous structure. Nano-structured materials have the potential to attenuate the strength of traveling shock waves because of their high surface-to-volume ratio. To investigate such interactions we have developed a molecular dynamics simulation model, based on Short Range Attractive interactions. A piston, modeled as a uni-directional repulsive force field translating at a prescribed velocity, impinges on a region of gas which is compressed to form a shock, which in turn is driven against an atomistic solid wall. Periodic boundary conditions are used in the directions orthogonal to the piston motion, and we have considered solids based on either embedded atom potentials (target structure) or tethered potential (rigid piston, holding wall). Velocity, temperature and stress fields are computed locally in both gas and solid regions, and displacements within the solid are interpreted in terms of its elastic constants. In this work we present results of the elastic behavior of solid structures subjected to shock wave impact and analysis of energy transport and absorption in porous materials. The results indicated that the presence of nano-porous material layers in front of a target wall reduced the stress magnitude detected inside and the energy deposited there by about 30 percent while, at the same time, its loading rate was decreased substantially.

  12. DockingShop: A Tool for Interactive Molecular Docking

    SciTech Connect

    Lu, Ting-Cheng; Max, Nelson L.; Ding, Jinhui; Bethel, E. Wes; Crivelli, Silvia N.

    2005-04-24

    Given two independently determined molecular structures, the molecular docking problem predicts the bound association, or best fit between them, while allowing for conformational changes of the individual molecules during construction of a molecular complex. Docking Shop is an integrated environment that permits interactive molecular docking by navigating a ligand or protein to an estimated binding site of a receptor with real-time graphical feedback of scoring factors as visual guides. Our program can be used to create initial configurations for a protein docking prediction process. Its output--the structure of aprotein-ligand or protein-protein complex--may serve as an input for aprotein docking algorithm, or an optimization process. This tool provides molecular graphics interfaces for structure modeling, interactive manipulation, navigation, optimization, and dynamic visualization to aid users steer the prediction process using their biological knowledge.

  13. Specific interactions between DNA and regulatory protein controlled by ligand-binding: Ab initio molecular simulation

    SciTech Connect

    Matsushita, Y. Murakawa, T. Shimamura, K. Oishi, M. Ohyama, T. Kurita, N.

    2015-02-27

    The catabolite activator protein (CAP) is one of the regulatory proteins controlling the transcription mechanism of gene. Biochemical experiments elucidated that the complex of CAP with cyclic AMP (cAMP) is indispensable for controlling the mechanism, while previous molecular simulations for the monomer of CAP+cAMP complex revealed the specific interactions between CAP and cAMP. However, the effect of cAMP-binding to CAP on the specific interactions between CAP and DNA is not elucidated at atomic and electronic levels. We here considered the ternary complex of CAP, cAMP and DNA in solvating water molecules and investigated the specific interactions between them at atomic and electronic levels using ab initio molecular simulations based on classical molecular dynamics and ab initio fragment molecular orbital methods. The results highlight the important amino acid residues of CAP for the interactions between CAP and cAMP and between CAP and DNA.

  14. Plasmonic interactions: from molecular plasmonics and Fano resonances to ferroplasmons.

    PubMed

    Passarelli, Nicolás; Pérez, Luis A; Coronado, Eduardo A

    2014-10-28

    Plasmon interactions are a subject of great interest from both the technological as well as the fundamental points of view. In this Perspective, we outline the great variety of physical phenomena that are produced by the interactions of localized surface plasmon resonance with molecular excitons; with other plasmonic nanostructures, particularly the Fano effect; and with nonplasmonic nanoparticles, such as the just-reported interaction with ferromagnetic nanoparticles. The theoretical as well as experimental challenges remaining to be elucidated are discussed.

  15. Molecular Determinants in Phagocyte-Bacteria Interactions.

    PubMed

    Kaufmann, Stefan H E; Dorhoi, Anca

    2016-03-15

    Phagocytes are crucial for host defense against bacterial pathogens. As first demonstrated by Metchnikoff, neutrophils and mononuclear phagocytes share the capacity to engulf, kill, and digest microbial invaders. Generally, neutrophils focus on extracellular, and mononuclear phagocytes on intracellular, pathogens. Reciprocally, extracellular pathogens often capitalize on hindering phagocytosis and killing of phagocytes, whereas intracellular bacteria frequently allow their engulfment and then block intracellular killing. As foreseen by Metchnikoff, phagocytes become highly versatile by acquiring diverse phenotypes, but still retaining some plasticity. Further, phagocytes engage in active crosstalk with parenchymal and immune cells to promote adjunctive reactions, including inflammation, tissue healing, and remodeling. This dynamic network allows the host to cope with different types of microbial invaders. Here we present an update of molecular and cellular mechanisms underlying phagocyte functions in antibacterial defense. We focus on four exemplary bacteria ranging from an opportunistic extracellular to a persistent intracellular pathogen. PMID:26982355

  16. Molecular contamination study by interaction of a molecular beam with a platinum surface

    NASA Technical Reports Server (NTRS)

    Nuss, H. E.

    1976-01-01

    The capability of molecular beam scattering from a solid surface is analyzed for identification of molecular contamination of the surface. The design and setup of the molecular beam source and the measuring setup for the application of a phase sensitive measuring technique for the determination of the scattered beam intensity are described. The scattering distributions of helium and nitrogen molecular beams interacting with a platinum surface were measured for different amounts of contamination from diffusion pump oil for surface temperatures ranging from 30 to 400 C. The results indicate the scattering of molecular beams from a platinum surface is a very sensitive method for detecting surface contamination.

  17. BIMOLECULAR FLUORESCENCE COMPLEMENTATION: VISUALIZATION OF MOLECULAR INTERACTIONS IN LIVING CELLS

    PubMed Central

    Kerppola, Tom K.

    2009-01-01

    A variety of experimental methods have been developed for the analysis of protein interactions. The majority of these methods either require disruption of the cells to detect molecular interactions or rely on indirect detection of the protein interaction. The bimolecular fluorescence complementation (BiFC) assay provides a direct approach for the visualization of molecular interactions in living cells and organisms. The BiFC approach is based on the facilitated association between two fragments of a fluorescent protein when the fragments are brought together by an interaction between proteins fused to the fragments. The BiFC approach has been used for visualization of interactions among a variety of structurally divers interaction partners in many different cell types and. It enables detection of transient complexes as well as complexes formed by a subpopulation of the interaction partners. It is essential to include negative controls in each experiment in which the interface between the interaction partners has been mutated or deleted. The BiFC assay has been adapted for simultaneous visualization of multiple protein complexes in the same cell and the competition for shared interaction partners. A ubiquitin-mediated fluorescence complementation (UbFC) assay has also been developed for visualization of the covalent modification of proteins by ubiquitin family peptides. These fluorescence complementation assays have a great potential to illuminate a variety of biological interactions in the future. PMID:18155474

  18. An investigation of counterrotating tip vortex interaction

    NASA Technical Reports Server (NTRS)

    Majjigi, R. K.; Uenishi, K.; Gliebe, P. R.

    1989-01-01

    A tip vortex interaction model originally developed for compressors has been extended and adapted for use with counterrotating open rotors. Comparison of available acoustic data with predictions (made with and without the tip vortex model included) illustrate the importance of this interaction effect. This report documents the analytical modeling, a limited experimental verification, and certain key parametric studies pertaining to the tip vortex as a noise source mechanism for the unsteady loading noise of counterrotating properllers.

  19. Speeding up biomolecular interactions by molecular sledding

    DOE PAGESBeta

    Turkin, Alexander; Zhang, Lei; Marcozzi, Alessio; Mangel, Walter F.; Herrmann, Andreas; van Oijen, Antoine M.

    2015-10-07

    In numerous biological processes associations involve a protein with its binding partner, an event that is preceded by a diffusion-mediated search bringing the two partners together. Often hindered by crowding in biologically relevant environments, three-dimensional diffusion can be slow and result in long bimolecular association times. Moreover, the initial association step between two binding partners often represents a rate-limiting step in biotechnologically relevant reactions. We also demonstrate the practical use of an 11-a.a. DNA-interacting peptide derived from adenovirus to reduce the dimensionality of diffusional search processes and speed up associations between biological macromolecules. We functionalize binding partners with the peptidemore » and demonstrate that the ability of the peptide to one-dimensionally diffuse along DNA results in a 20-fold reduction in reaction time. We also show that modifying PCR primers with the peptide sled enables significant acceleration of standard PCR reactions.« less

  20. Speeding up biomolecular interactions by molecular sledding

    SciTech Connect

    Turkin, Alexander; Zhang, Lei; Marcozzi, Alessio; Mangel, Walter F.; Herrmann, Andreas; van Oijen, Antoine M.

    2015-10-07

    In numerous biological processes associations involve a protein with its binding partner, an event that is preceded by a diffusion-mediated search bringing the two partners together. Often hindered by crowding in biologically relevant environments, three-dimensional diffusion can be slow and result in long bimolecular association times. Moreover, the initial association step between two binding partners often represents a rate-limiting step in biotechnologically relevant reactions. We also demonstrate the practical use of an 11-a.a. DNA-interacting peptide derived from adenovirus to reduce the dimensionality of diffusional search processes and speed up associations between biological macromolecules. We functionalize binding partners with the peptide and demonstrate that the ability of the peptide to one-dimensionally diffuse along DNA results in a 20-fold reduction in reaction time. We also show that modifying PCR primers with the peptide sled enables significant acceleration of standard PCR reactions.

  1. Molecular interactions and crystal packing in nematogen: Computational thermodynamic approach

    NASA Astrophysics Data System (ADS)

    Lakshmi Praveen, P.; Ojha, Durga P.

    2011-10-01

    A computational thermodynamic approach of molecular interactions in a nematogen p-n-alkyl benzoic acid ( nBAC) molecule with an alkyl group butyl (4BAC) has been carried out with respect to translational and orientational motion. The atomic net charge and dipole moment at each atomic center were evaluated using the complete neglect differential overlap (CNDO/2) method. The modified Rayleigh-Schrödinger perturbation theory along with multicentered-multipole expansion method were employed to evaluate long-range intermolecular interactions, while a 6-exp potential function was assumed for short-range interactions. Various possible geometrical arrangements of molecular pairs with regard to different energy components were considered, and the energetically favorable configuration was found to understand the crystal packing picture. Furthermore, these interaction energy values are taken as input to calculate the configurational entropy at room temperature (300 K), nematic-isotropic transition temperature (386 K) and above transition temperature (450 K) during different modes of interactions. An attempt has been made to describe interactions in a nematogen at molecular level, through which one can simplify the system to make the model computationally feasible in understanding the delicate interplay between energy and entropy, that accounts for mesomorphism and there by to analyze the molecular structure of a nematogen.

  2. Developing a Molecular Roadmap of Drug-Food Interactions

    PubMed Central

    Jensen, Kasper; Ni, Yueqiong; Panagiotou, Gianni; Kouskoumvekaki, Irene

    2015-01-01

    Recent research has demonstrated that consumption of food -especially fruits and vegetables- can alter the effects of drugs by interfering either with their pharmacokinetic or pharmacodynamic processes. Despite the recognition of such drug-food associations as an important element for successful therapeutic interventions, a systematic approach for identifying, predicting and preventing potential interactions between food and marketed or novel drugs is not yet available. The overall objective of this work was to sketch a comprehensive picture of the interference of ∼ 4,000 dietary components present in ∼1800 plant-based foods with the pharmacokinetics and pharmacodynamics processes of medicine, with the purpose of elucidating the molecular mechanisms involved. By employing a systems chemical biology approach that integrates data from the scientific literature and online databases, we gained a global view of the associations between diet and dietary molecules with drug targets, metabolic enzymes, drug transporters and carriers currently deposited in DrugBank. Moreover, we identified disease areas and drug targets that are most prone to the negative effects of drug-food interactions, showcasing a platform for making recommendations in relation to foods that should be avoided under certain medications. Lastly, by investigating the correlation of gene expression signatures of foods and drugs we were able to generate a completely novel drug-diet interactome map. PMID:25668218

  3. Conservation of molecular interactions stabilizing bovine and mouse rhodopsin †

    PubMed Central

    Kawamura, Shiho; Colozo, Alejandro T.; Müller, Daniel J.; Park, Paul S.-H.

    2010-01-01

    Rhodopsin is the light receptor that initiates phototransduction in rod photoreceptor cells. The structure and function of rhodopsin is tightly linked to molecular interactions that stabilize and determine the receptor's functional state. Single-molecule force spectroscopy (SMFS) was used to localize and quantify molecular interactions that structurally stabilize bovine and mouse rhodopsin from native disc membranes of rod photoreceptor cells. The mechanical unfolding of bovine and mouse rhodopsin revealed nine major unfolding intermediates, each intermediate defining a structurally stable segment in the receptor. These stable structural segments had similar localization and occurrence in both bovine and mouse samples. For each structural segment, parameters describing their unfolding energy barrier were determined by dynamic SMFS. No major differences were observed between bovine and mouse rhodopsin thereby implying that the structures of both rhodopsins are largely stabilized by similar molecular interactions. PMID:21038881

  4. Molecular modeling of protein-glycosaminoglycan interactions.

    PubMed

    Cardin, A D; Weintraub, H J

    1989-01-01

    Forty-nine regions in 21 proteins were identified as potential heparin-binding sites based on the sequence organizations of their basic and nonbasic residues. Twelve known heparin-binding sequences in vitronectin, apolipoproteins E and B-100, and platelet factor 4 were used to formulate two search strings for identifying potential heparin-binding regions in other proteins. Consensus sequences for glycosaminoglycan recognition were determined as [-X-B-B-X-B-X-] and [-X-B-B-B-X-X-B-X-] where B is the probability of a basic residue and X is a hydropathic residue. Predictions were then made as to the heparin-binding domains in endothelial cell growth factor, purpurin, and antithrombin-III. Many of the natural sequences conforming to these consensus motifs show prominent amphipathic periodicities having both alpha-helical and beta-strand conformations as determined by predictive algorithms and circular dichroism studies. The heparin-binding domain of vitronectin was modeled and formed a hydrophilic pocket that wrapped around and folded over a heparin octasaccharide, yielding a complementary structure. We suggest that these consensus sequence elements form potential nucleation sites for the recognition of polyanions in proteins and may provide a useful guide in identifying heparin-binding regions in other proteins. The possible relevance of protein-glycosaminoglycans interactions in atherosclerosis is discussed. PMID:2463827

  5. Studying Interactions by Molecular Dynamics Simulations at High Concentration

    PubMed Central

    Fogolari, Federico; Corazza, Alessandra; Toppo, Stefano; Tosatto, Silvio C. E.; Viglino, Paolo; Ursini, Fulvio; Esposito, Gennaro

    2012-01-01

    Molecular dynamics simulations have been used to study molecular encounters and recognition. In recent works, simulations using high concentration of interacting molecules have been performed. In this paper, we consider the practical problems for setting up the simulation and to analyse the results of the simulation. The simulation of beta 2-microglobulin association and the simulation of the binding of hydrogen peroxide by glutathione peroxidase are provided as examples. PMID:22500085

  6. Investigation of synthetic molecular recognition for biosensing applications

    NASA Astrophysics Data System (ADS)

    Stratis-Cullum, Dimitra N.; McMasters, Sun; Sooter, Letha J.; Pellegrino, Paul M.

    2007-04-01

    A fundamental understanding of the factors which influence binding performance is critical to any technology or methodology relying on molecular recognition of a specific target species. For the Army, there is a growing need for a basic understanding of these interactions with traditional recognition elements (e.g., antibodies) in non-traditional environmental conditions, such as with new and emerging threats. There is a similar need for building a base of knowledge on non-traditional affinity ligands that are biomimetic or biosynthetic in nature. In this paper, specific research at the Army Research Laboratory towards the development, evaluation and use of synthetic affinity ligands for sensing applications is discussed. This includes the results of our investigations of aptamer-based affinity ligands targeting Campylobacter jejuni. Using capillary electrophoretic techniques, the relative binding affinities of the aptamer ligands towards the target pathogen as well as the degree of cross-reactivity with other food borne-pathogens (i.e., Escherichia coli O157:H7 and Salmonella typhimurium) were evaluated. Current progress towards the development of synthetic affinity ligands for sensing applications will also be discussed.

  7. Origin of molecular conformational stability: perspectives from molecular orbital interactions and density functional reactivity theory.

    PubMed

    Liu, Shubin; Schauer, Cynthia K

    2015-02-01

    To have a quantitative understanding about the origin of conformation stability for molecular systems is still an unaccomplished task. Frontier orbital interactions from molecular orbital theory and energy partition schemes from density functional reactivity theory are the two approaches available in the literature that can be used for this purpose. In this work, we compare the performance of these approaches for a total of 48 simple molecules. We also conduct studies to flexibly bend bond angles for water, carbon dioxide, borane, and ammonia molecules to obtain energy profiles for these systems over a wide range of conformations. We find that results from molecular orbital interactions using frontier occupied orbitals such as the highest occupied molecular orbital and its neighbors are only qualitatively, at most semi-qualitatively, trustworthy. To obtain quantitative insights into relative stability of different conformations, the energy partition approach from density functional reactivity theory is much more reliable. We also find that the electrostatic interaction is the dominant descriptor for conformational stability, and steric and quantum effects are smaller in contribution but their contributions are indispensable. Stable molecular conformations prefer to have a strong electrostatic interaction, small molecular size, and large exchange-correlation effect. This work should shed new light towards establishing a general theoretical framework for molecular stability.

  8. Origin of molecular conformational stability: Perspectives from molecular orbital interactions and density functional reactivity theory

    SciTech Connect

    Liu, Shubin E-mail: schauer@unc.edu; Schauer, Cynthia K. E-mail: schauer@unc.edu

    2015-02-07

    To have a quantitative understanding about the origin of conformation stability for molecular systems is still an unaccomplished task. Frontier orbital interactions from molecular orbital theory and energy partition schemes from density functional reactivity theory are the two approaches available in the literature that can be used for this purpose. In this work, we compare the performance of these approaches for a total of 48 simple molecules. We also conduct studies to flexibly bend bond angles for water, carbon dioxide, borane, and ammonia molecules to obtain energy profiles for these systems over a wide range of conformations. We find that results from molecular orbital interactions using frontier occupied orbitals such as the highest occupied molecular orbital and its neighbors are only qualitatively, at most semi-qualitatively, trustworthy. To obtain quantitative insights into relative stability of different conformations, the energy partition approach from density functional reactivity theory is much more reliable. We also find that the electrostatic interaction is the dominant descriptor for conformational stability, and steric and quantum effects are smaller in contribution but their contributions are indispensable. Stable molecular conformations prefer to have a strong electrostatic interaction, small molecular size, and large exchange-correlation effect. This work should shed new light towards establishing a general theoretical framework for molecular stability.

  9. 2004 Atomic and Molecular Interactions Gordon Research Conference

    SciTech Connect

    Dr. Paul J. Dagdigian

    2004-10-25

    The 2004 Gordon Research Conference on Atomic and Molecular Interactions was held July 11-16 at Colby-Sawyer College, New London, New Hampshire. This latest edition in a long-standing conference series featured invited talks and contributed poster papers on dynamics and intermolecular interactions in a variety of environments, ranging from the gas phase through surfaces and condensed media. A total of 90 conferees participated in the conference.

  10. Molecular interaction maps as information organizers and simulation guides

    NASA Astrophysics Data System (ADS)

    Kohn, Kurt W.

    2001-03-01

    A graphical method for mapping bioregulatory networks is presented that is suited for the representation of multimolecular complexes, protein modifications, as well as actions at cell membranes and between protein domains. The symbol conventions defined for these molecular interaction maps are designed to accommodate multiprotein assemblies and protein modifications that can generate combinatorially large numbers of molecular species. Diagrams can either be "heuristic," meaning that detailed knowledge of all possible reaction paths is not required, or "explicit," meaning that the diagrams are totally unambiguous and suitable for simulation. Interaction maps are linked to annotation lists and indexes that provide ready access to pertinent data and references, and that allow any molecular species to be easily located. Illustrative interaction maps are included on the domain interactions of Src, transcription control of E2F-regulated genes, and signaling from receptor tyrosine kinase through phosphoinositides to Akt/PKB. A simple method of going from an explicit interaction diagram to an input file for a simulation program is outlined, in which the differential equations need not be written out. The role of interaction maps in selecting and defining systems for modeling is discussed.

  11. Theoretical investigation of gas-surface interactions

    NASA Technical Reports Server (NTRS)

    Dyall, Kenneth G.

    1990-01-01

    A Dirac-Hartree-Fock code was developed for polyatomic molecules. The program uses integrals over symmetry-adapted real spherical harmonic Gaussian basis functions generated by a modification of the MOLECULE integrals program. A single Gaussian function is used for the nuclear charge distribution, to ensure proper boundary conditions at the nuclei. The Gaussian primitive functions are chosen to satisfy the kinetic balance condition. However, contracted functions which do not necessarily satisfy this condition may be used. The Fock matrix is constructed in the scalar basis and transformed to a jj-coupled 2-spinor basis before diagonalization. The program was tested against numerical results for atoms with a Gaussian nucleus and diatomic molecules with point nuclei. The energies converge on the numerical values as the basis set size is increased. Full use of molecular symmetry (restricted to D sub 2h and subgroups) is yet to be implemented.

  12. Spectral tuning of organic nanocolloids by controlled molecular interactions.

    PubMed

    Spillmann, Christopher M; Naciri, Jawad; Anderson, George P; Chen, Mu-San; Ratna, Banahalli R

    2009-10-27

    The controlled self-assembly of molecules and interactions between them remain a challenge in creating tunable and functional organic nanostructures. One class of molecular systems that has proven useful for incorporating tunable functionality at different length scales is liquid crystals (LCs) due to its ability to inherently self-organize. Here we present a novel approach to utilize the self-assembly of polymerizable liquid crystals to control the molecular aggregation of stable fluorescent chromophores and create a unique class of organic fluorescent nanocolloids. By adjusting the ratio between the dye and LC molecules inside the nanocolloids, we demonstrate the ability to control the molecular interactions and tune the fluorescent emission spectra of nanocolloid populations under single wavelength excitation. The single absorption spectrum and multiple emission spectra are highly desirable and reminiscent of the spectroscopic signature of quantum dots. These novel fluorescent nanocolloids have broad potential applications in fluorescent imaging and biological labeling.

  13. Gesture Interaction Browser-Based 3D Molecular Viewer.

    PubMed

    Virag, Ioan; Stoicu-Tivadar, Lăcrămioara; Crişan-Vida, Mihaela

    2016-01-01

    The paper presents an open source system that allows the user to interact with a 3D molecular viewer using associated hand gestures for rotating, scaling and panning the rendered model. The novelty of this approach is that the entire application is browser-based and doesn't require installation of third party plug-ins or additional software components in order to visualize the supported chemical file formats. This kind of solution is suitable for instruction of users in less IT oriented environments, like medicine or chemistry. For rendering various molecular geometries our team used GLmol (a molecular viewer written in JavaScript). The interaction with the 3D models is made with Leap Motion controller that allows real-time tracking of the user's hand gestures. The first results confirmed that the resulting application leads to a better way of understanding various types of translational bioinformatics related problems in both biomedical research and education. PMID:27350455

  14. Gesture Interaction Browser-Based 3D Molecular Viewer.

    PubMed

    Virag, Ioan; Stoicu-Tivadar, Lăcrămioara; Crişan-Vida, Mihaela

    2016-01-01

    The paper presents an open source system that allows the user to interact with a 3D molecular viewer using associated hand gestures for rotating, scaling and panning the rendered model. The novelty of this approach is that the entire application is browser-based and doesn't require installation of third party plug-ins or additional software components in order to visualize the supported chemical file formats. This kind of solution is suitable for instruction of users in less IT oriented environments, like medicine or chemistry. For rendering various molecular geometries our team used GLmol (a molecular viewer written in JavaScript). The interaction with the 3D models is made with Leap Motion controller that allows real-time tracking of the user's hand gestures. The first results confirmed that the resulting application leads to a better way of understanding various types of translational bioinformatics related problems in both biomedical research and education.

  15. VIBE: A virtual biomolecular environment for interactive molecular modeling

    SciTech Connect

    Cruz-Neira, C.; Langley, R.; Bash, P.A.

    1996-12-31

    Virtual reality tightly coupled to high performance computing and communications ushers in a new era for the study of molecular recognition and the rational design of pharmaceutical compounds. We have created a Virtual Biomolecular Environment (VIBE), which consists of (1) massively parallel computing to simulate the physical and chemical properties of a molecular system, (2) the Cave Automatic Virtual Environment (CAVE) for immersive display and interaction with the molecular system, and (3) a high-speed network interface to exchange data between the simulation and the CAVE. VIBE enables molecular scientists to have a visual, auditory, and haptic experience with a chemical system, while simultaneously manipulating its physical properties by steering, in real-time, a simulation executed on a supercomputer. We demonstrate the characteristics of VIBE using an HIV protease-cyclic urea inhibitor complex. 22 refs., 4 figs.

  16. Growth mechanism, electronic spectral investigation and molecular orbital studies of L-prolinium phosphate.

    PubMed

    Liu, Xiaojing; Sun, Xin; Xu, Xijin; Sun, Ping

    2015-01-01

    By using atomic force microscopy, birth and spread has proved to be the primary growth mechanism for L-prolinium phosphate (LPP). The phenomenon of newly formed islands expanding to the edge of the preceding terrace was observed. The optimized molecular structure and the molecular properties were calculated by density functional theory method. Natural bond orbital analysis was carried out to demonstrate the various inter and intramolecular interactions that are responsible for the stabilization of LPP leading to high NLO activity. Molecular electrostatic potential, frontier molecular orbital analysis and thermodynamic properties were investigated to get a better insight of the molecular properties. Global and local reactivity descriptors were computed to predict the reactivity and reactive sites on the molecules. Non-linear optical (NLO) properties such as the total dipole moment (μ) and first order hyperopolarizability (β) were also calculated to predict NLO behavior.

  17. Molecular Interactions between a Novel Soybean Oil-Based Polymer and Doxorubicin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A novel soybean oil-based polymer, hydrolyzed polymers of epoxidized soybean oil (HPESO), was developed and investigated for drug delivery. This work was aimed at determining the molecular interactions between HPESO and doxorubicin (DOX), an anticancer drug. Powder X-ray diffraction, ATR-FTIR and ...

  18. Quantitative investigation of murine cytomegalovirus nucleocapsid interaction.

    PubMed

    Buser, Christopher; Fleischer, Frank; Mertens, Thomas; Michel, Detlef; Schmidt, Volker; Walther, Paul

    2007-10-01

    In this study, we quantitatively investigate the role of the M97 protein for viral morphogenesis in murine cytomegalovirus (MCMV)-infected fibroblast cells. For this purpose, a statistical analysis is performed for the spatial distribution of nuclear B-capsids (devoid of DNA, containing the scaffold) and C-capsids (filled with DNA). Cell nuclei infected with either wild-type or an M97 deletion mutant were compared. Univariate and multivariate point process characteristics (like Ripley's K-function, the L-function and the nearest neighbour distance distribution function) are investigated in order to describe and quantify the effects that the deletion of M97 causes to the process of DNA packaging into nucleocapsids. The estimation of the function L(r) -r reveals that with respect to the wild type there is an increased frequency of point pairs at a very short distance (less than approximately 100 nm) for both the B-capsids as well as for the C-capsids. For the M97 deletion mutant type this is no longer true. Here only the C-capsids show such a clustering behaviour, whereas for B-capsids it is almost nonexistant. Estimations of functionals such as the nearest neighbour distance distribution function confirmed these results. Thereby, a quantification is provided for the effect that the deletion of M97 leads to a loss of typical nucleocapsid clustering in MCMV-infected nuclei. PMID:17910700

  19. Generating interactive molecular documentaries using a library of graphical actions.

    PubMed

    Pulavarthi, P; Chiang, R; Altman, R B

    2000-01-01

    Paper-based publishing of scientific articles limits the types of presentations that can be used. The emergence of electronic publishing has created opportunities to increase the range of formats available for conveying scientific content. We introduce the Graphical Explanation Markup Language, GEML, implemented as an XML format for defining molecular documentaries which exploit the interactive capabilities of electronic publishing. GEML builds upon existing molecular structure definitions such as the Protein Data Bank (PDB) standard file format. GEML provides a library of gestures (or actions) commonly used for structural explanations, and is extensible. XML allows us to separate explicit statements about how to highlight a molecular structure from the implementation of these instructions. We also present GEIS (Generator of Explanatory Interactive Systems), a program that takes as input a GEML documentary definition file and produces all the files necessary for an interactive, web-based molecular documentary. To demonstrate GEML and GEIS, we constructed a documentary capturing the difficult 3D notions expressed in two selected published reports about human topoisomerase I. We have created a prototype Java application, GEMLBuilder, as an editor of GEML files. PMID:10902175

  20. Evolution & Phylogenetic Analysis: Classroom Activities for Investigating Molecular & Morphological Concepts

    ERIC Educational Resources Information Center

    Franklin, Wilfred A.

    2010-01-01

    In a flexible multisession laboratory, students investigate concepts of phylogenetic analysis at both the molecular and the morphological level. Students finish by conducting their own analysis on a collection of skeletons representing the major phyla of vertebrates, a collection of primate skulls, or a collection of hominid skulls.

  1. Ab initio molecular simulations on specific interactions between amyloid beta and monosaccharides

    NASA Astrophysics Data System (ADS)

    Nomura, Kazuya; Okamoto, Akisumi; Yano, Atsushi; Higai, Shin'ichi; Kondo, Takashi; Kamba, Seiji; Kurita, Noriyuki

    2012-09-01

    Aggregation of amyloid β (Aβ) peptides, which is a key pathogenetic event in Alzheimer's disease, can be caused by cell-surface saccharides. We here investigated stable structures of the solvated complexes of Aβ with some types of monosaccharides using molecular simulations based on protein-ligand docking and classical molecular mechanics methods. Moreover, the specific interactions between Aβ and the monosaccharides were elucidated at an electronic level by ab initio fragment molecular orbital calculations. Based on the results, we proposed which type of monosaccharide prefers to have large binding affinity to Aβ and inhibit the Aβ aggregation.

  2. Theoretical investigation of gas-surface interactions

    NASA Technical Reports Server (NTRS)

    Dyall, Kenneth G.

    1994-01-01

    The goal of this project was to develop computational tools for the calculation of the electronic structure of molecules containing heavy atoms, and to use these tools in the study of catalytic processes, with the overall objective of gaining an understanding of the catalytic process which could be used to design more efficient catalysts. The main catalytic system of interest was the combustion of hydrogen on platinum surfaces. Under this project, a flexible Dirac-Hartree-Fock (DHF) program has been developed, a code to calculate DHF correlation energies at the second-order Moeller-Plesset perturbation (PP2) level is almost complete, and code to include correlation at the MCSCF and MCSCF/MP2 level is planned. The tools so far developed have been validated and used to calibrate some more approximate methods, and applied to investigate the importance of relativistic effects in the bonding of hydrogen to platinum.

  3. Investigation of the ion beryllium surface interaction

    SciTech Connect

    Guseva, M.I.; Birukov, A.Yu.; Gureev, V.M.

    1995-09-01

    The self -sputtering yield of the Be was measured. The energy dependence of the Be self-sputtering yield agrees well with that calculated by W. Eckstein et. al. Below 770 K the self-sputtering yield is temperature independent; at T{sub irr}.> 870 K it increases sharply. Hot-pressed samples at 370 K were implanted with monoenergetic 5 keV hydrogen ions and with a stationary plasma (flux power {approximately} 5 MW/m{sup 2}). The investigation of hydrogen behavior in beryllium shows that at low doses hydrogen is solved, but at doses {ge} 5x10{sup 22} m{sup -2} the bubbles and channels are formed. It results in hydrogen profile shift to the surface and decrease of its concentration. The sputtering results in further concentration decrease at doses > 10{sup 25}m{sup -2}.

  4. Molecular and Cellular Quantitative Microscopy: theoretical investigations, technological developments and applications to neurobiology

    NASA Astrophysics Data System (ADS)

    Esposito, Alessandro

    2006-05-01

    This PhD project aims at the development and evaluation of microscopy techniques for the quantitative detection of molecular interactions and cellular features. The primarily investigated techniques are Fαrster Resonance Energy Transfer imaging and Fluorescence Lifetime Imaging Microscopy. These techniques have the capability to quantitatively probe the biochemical environment of fluorophores. An automated microscope capable of unsupervised operation has been developed that enables the investigation of molecular and cellular properties at high throughput levels and the analysis of cellular heterogeneity. State-of-the-art Förster Resonance Energy Transfer imaging, Fluorescence Lifetime Imaging Microscopy, Confocal Laser Scanning Microscopy and the newly developed tools have been combined with cellular and molecular biology techniques for the investigation of protein-protein interactions, oligomerization and post-translational modifications of α-Synuclein and Tau, two proteins involved in Parkinson’s and Alzheimer’s disease, respectively. The high inter-disciplinarity of this project required the merging of the expertise of both the Molecular Biophysics Group at the Debye Institute - Utrecht University and the Cell Biophysics Group at the European Neuroscience Institute - Gαttingen University. This project was conducted also with the support and the collaboration of the Center for the Molecular Physiology of the Brain (Göttingen), particularly with the groups associated with the Molecular Quantitative Microscopy and Parkinson’s Disease and Aggregopathies areas. This work demonstrates that molecular and cellular quantitative microscopy can be used in combination with high-throughput screening as a powerful tool for the investigation of the molecular mechanisms of complex biological phenomena like those occurring in neurodegenerative diseases.

  5. Molecular Interaction between Magainin 2 and Model Membranes in Situ

    PubMed Central

    Nguyen, Khoi; Le Clair, Stéphanie V.; Ye, Shuji; Chen, Zhan

    2009-01-01

    In this paper, we investigated the molecular interactions of Magainin 2 with model cell membranes using Sum Frequency Generation (SFG) vibrational spectroscopy and Attenuated Total Reflectance – Fourier Transform Infrared spectroscopy (ATR-FTIR). Symmetric 1-Palmitoyl-2-Oleoyl-sn-Glycero-3-[Phospho-rac-(1-glycerol)] (POPG) and 1-Palmitoyl-2-Oleoyl-sn-Glycero-3-Phosphocholine (POPC) bilayers, which model the bacterial and mammalian cell membranes respectively, were used in the studies. It was observed by SFG that Magainin 2 orients relatively parallel to the POPG lipid bilayer surface at low solution concentrations, around 200 nM. When increasing the Magainin 2 concentration to 800 nM, both SFG and ATR-FTIR results indicate that Magainin 2 molecules insert into the POPG bilayer and adopt a transmembrane orientation with an angle of about 20 degrees from the POPG bilayer normal. For the POPC bilayer, even at a much higher peptide concentration of 2.0 µM, no ATR-FTIR signal was detected. For this concentration on POPC, SFG studies indicated that Magainin 2 molecules adopt an orientation nearly parallel to the bilayer surface, with an orientation angle of 75 degrees from the surface normal. This shows that SFG has a much better detection limit than ATR-FTIR and can therefore be applied to study interfacial molecules with much lower surface coverage. This Magainin 2 orientation study and further investigation of the lipid bilayer SFG signals support the proposed toroidal pore model for the antimicrobial activity of Magainin 2. PMID:19728722

  6. Theoretical investigation of gas-surface interactions

    NASA Technical Reports Server (NTRS)

    Dyall, Kenneth G.

    1992-01-01

    The investigation into the appearance of intruder states from the negative continuum when some of the two-electron integrals were omitted was completed. The work shows that, provided all integrals involving core contracted functions in an atomic general contraction are included, or that the core functions are radially localized, meaningful results are obtained and intruder states do not appear. In the area of program development, the Dirac-Hartree-Fock (DHF) program for closed-shell polyatomic molecules was extended to permit Kramers-restricted open-shell DHF calculations with one electron in an open shell or one hole in a closed shell, or state-averaged DHF calculations over several particle or hole doublet states. One application of the open-shell code was to the KO molecule. Another major area of program development is the transformation of integrals from the scalar basis in which they are generated to the 2-spinor basis employed in parts of the DHF program, and hence to supermatrix form. Particularly concerning the omission of small component integrals, and with increase in availability of disk space, it is now possible to consider transforming the integrals. The use of ordered integrals, either in the scalar basis or in the 2-spinor basis, would considerably speed up the construction of the Fock matrix, and even more so if supermatrices were constructed. A considerable amount of effort was spent on analyzing the integral ordering and tranformation for the DHF program. The work of assessing the reliability of the relativistic effective core potentials (RECPs) was continued with calculation of the group IV monoxides. The perturbation of the metal atom provided by oxygen is expected to be larger than that provided by hydrogen and thus provide a better test of the qualification of the RECPs. Calculations on some platinum hydrides were carried out at nonrelativistic (NR), perturbation theory (PT) and DHF levels. Reprints of four papers describing this work are

  7. Rheological investigation of highly filled polymers: Effect of molecular weight

    NASA Astrophysics Data System (ADS)

    Hnatkova, Eva; Hausnerova, Berenika; Hales, Andrew; Jiranek, Lukas; Vera, Juan Miguel Alcon

    2015-04-01

    The paper deals with rheological properties of highly filled polymers used in powder injection molding. Within the experimental framework seven PIM feedstocks based on superalloy Inconel 718 powder were prepared. Each feedstock contains the fixed amount of powder loading and the same composition of binder system consisting of three components: polyethylene glycol (PEG) differing in molecular weight, poly (methyl methacrylate) (PMMA) and stearic acid (SA). The aim is to investigate the influence of PEG's molecular weight on the flow properties of feedstocks. Non-Newtonian indices, representing the shear rate sensitivity of the feedstocks, are obtained from a polynomial fit, and found to vary within measured shear rates range from 0.2 to 0.8. Temperature effect is considered via activation energies, showing decreasing trend with increasing of molecular weight of PEG (except of feedstock containing 1,500 g.mol-1 PEG).

  8. Bone regeneration: molecular and cellular interactions with calcium phosphate ceramics

    PubMed Central

    Barrère, Florence; van Blitterswijk, Clemens A; de Groot, Klaas

    2006-01-01

    Calcium phosphate bioceramics are widely used in orthopedic and dental applications and porous scaffolds made of them are serious candidates in the field of bone tissue engineering. They have superior properties for the stimulation of bone formation and bone bonding, both related to the specific interactions of their surface with the extracellular fluids and cells, ie, ionic exchanges, superficial molecular rearrangement and cellular activity. PMID:17717972

  9. Experimental investigation of interactions between proteins and carbon nanomaterials

    NASA Astrophysics Data System (ADS)

    Sengupta, Bishwambhar

    The global market for nanomaterials based products is forecasted to reach $1 trillion per annum per annum for 2015. Engineered nanomaterials (ENMs) exhibit unique physicochemical properties with potential to impact diverse aspects of society through applications in electronics, renewable energy, and medicine. While the research and proposed applications of ENMs continue to grow rapidly, the health and safety of ENMs still remains a major concern to the public as well as to policy makers and funding agencies. It is now widely accepted that focused efforts are needed for identifying the list of physicochemical descriptors of ENM before they can be evaluated for nanotoxicity and biological response. This task is surprisingly challenging, as many physicochemical properties of ENMs are closely inter related and cannot be varied independently (e.g. increasing the size of an ENM can introduce additional defects). For example, varying toxic response may ensue due to different methods of nanomaterial preparation, dissimilar impurities and defects. Furthermore, the inadvertent coating of proteins on ENM surface in any biological milieu results in the formation of the so-called "protein/bio-corona" which can in turn alter the fate of ENMs and their biological response. Carbon nanomaterials (CNMs) such as carbon nanotubes, graphene, and graphene oxide are widely used ENMs. It is now known that defects in CNMs play an important role not only in materials properties but also in the determination of how materials interact at the nano-bio interface. In this regard, this work investigates the influence of defect-induced hydrophilicity on the bio-corona formation using micro Raman, photoluminescence, infrared spectroscopy, electrochemistry, and molecular dynamics simulations. Our results show that the interaction of proteins (albumin and fibrinogen) with CNMs is strongly influenced by charge transfer between them, inducing protein unfolding which enhances conformational entropy and

  10. Energy level realignment in weakly interacting donor-acceptor binary molecular networks.

    PubMed

    Zhong, Jian-Qiang; Qin, Xinming; Zhang, Jia-Lin; Kera, Satoshi; Ueno, Nobuo; Wee, Andrew Thye Shen; Yang, Jinlong; Chen, Wei

    2014-02-25

    Understanding the effect of intermolecular and molecule-substrate interactions on molecular electronic states is key to revealing the energy level alignment mechanism at organic-organic heterojunctions or organic-inorganic interfaces. In this paper, we investigate the energy level alignment mechanism in weakly interacting donor-acceptor binary molecular superstructures, comprising copper hexadecafluorophthalocyanine (F16CuPc) intermixed with copper phthalocyanine (CuPc), or manganese phthalocynine (MnPc) on graphite. The molecular electronic structures have been systematically studied by in situ ultraviolet photoelectron spectroscopy (UPS) and low-temperature scanning tunneling microscopy/spectroscopy (LT-STM/STS) experiments and corroborated by density functional theory (DFT) calculations. As demonstrated by the UPS and LT-STM/STS measurements, the observed unusual energy level realignment (i.e., a large downward shift in donor HOMO level and a corresponding small upward shift in acceptor HOMO level) in the CuPc-F16CuPc binary superstructures originates from the balance between intermolecular and molecule-substrate interactions. The enhanced intermolecular interactions through the hydrogen bonding between neighboring CuPc and F16CuPc can stabilize the binary superstructures and modify the local molecular electronic states. The obvious molecular energy level shift was explained by gap-state-mediated interfacial charge transfer. PMID:24433044

  11. 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.

  12. Topology and static response of interaction networks in molecular biology.

    PubMed

    Radulescu, Ovidiu; Lagarrigue, Sandrine; Siegel, Anne; Veber, Philippe; Le Borgne, Michel

    2006-02-22

    We introduce a mathematical framework describing static response of networks occurring in molecular biology. This formalism has many similarities with the Laplace-Kirchhoff equations for electrical networks. We introduce the concept of graph boundary and we show how the response of the biological networks to external perturbations can be related to the Dirichlet or Neumann problems for the corresponding equations on the interaction graph. Solutions to these two problems are given in terms of path moduli (measuring path rigidity with respect to the propagation of interaction along the graph). Path moduli are related to loop products in the interaction graph via generalized Mason-Coates formulae. We apply our results to two specific biological examples: the lactose operon and the genetic regulation of lipogenesis. Our applications show consistency with experimental results and in the case of lipogenesis check some hypothesis on the behaviour of hepatic fatty acids on fasting. PMID:16849230

  13. Topology and static response of interaction networks in molecular biology

    PubMed Central

    Radulescu, Ovidiu; Lagarrigue, Sandrine; Siegel, Anne; Veber, Philippe; Le Borgne, Michel

    2005-01-01

    We introduce a mathematical framework describing static response of networks occurring in molecular biology. This formalism has many similarities with the Laplace–Kirchhoff equations for electrical networks. We introduce the concept of graph boundary and we show how the response of the biological networks to external perturbations can be related to the Dirichlet or Neumann problems for the corresponding equations on the interaction graph. Solutions to these two problems are given in terms of path moduli (measuring path rigidity with respect to the propagation of interaction along the graph). Path moduli are related to loop products in the interaction graph via generalized Mason–Coates formulae. We apply our results to two specific biological examples: the lactose operon and the genetic regulation of lipogenesis. Our applications show consistency with experimental results and in the case of lipogenesis check some hypothesis on the behaviour of hepatic fatty acids on fasting. PMID:16849230

  14. Effective interactions in molecular dynamics simulations of lysozyme solutions

    NASA Astrophysics Data System (ADS)

    Pellicane, Giuseppe; Sarkisov, Lev

    2014-09-01

    In this article we explore a problem of effective interactions between two rotationally restrained lysozyme molecules forming a crystal contact in aqueous solution. We perform non-equilibrium molecular dynamics simulations in order to estimate the interaction energy as a function of the distance between the two proteins obtained from direct application of the Jarzynski equality (JE), and compare it with that calculated by means of another non-equilibrium approach (Forward-Reverse method) and constrained force methods. The performance of the JE equality when applied to solvated protein interactions is discussed. All of the equilibrium and non-equilibrium methods show clear evidence that the potentials of mean force (PMF) are short-ranged, do not exceed few kTs, and that there is an accumulation of anions in the presence of hydrophobic surfaces.

  15. Binding properties of palmatine to DNA: spectroscopic and molecular modeling investigations.

    PubMed

    Mi, Ran; Tu, Bao; Bai, Xiao-Ting; Chen, Jun; Ouyang, Yu; Hu, Yan-Jun

    2015-12-01

    Palmatine, an isoquinoline alkaloid, is an important medicinal herbal extract with diverse pharmacological and biological properties. In this work, spectroscopic and molecular modeling approaches were employed to reveal the interaction between palmatine and DNA isolated from herring sperm. The absorption spectra and iodide quenching results indicated that groove binding was the main binding mode of palmatine to DNA. Fluorescence studies indicated that the binding constant (K) of palmatine and DNA was ~ 10(4)L·mol(-1). The associated thermodynamic parameters, ΔG, ΔH, and ΔS, indicated that hydrogen bonds and van der Waals forces played major roles in the interaction. The effects of chemical denaturant, thermal denaturation and pH on the interaction were investigated and provided further support for the groove binding mode. In addition to experimental approaches, molecular modeling was conducted to verify binding pattern of palmatine-DNA.

  16. Molecular Basis of Chemokine CXCL5-Glycosaminoglycan Interactions.

    PubMed

    Sepuru, Krishna Mohan; Nagarajan, Balaji; Desai, Umesh R; Rajarathnam, Krishna

    2016-09-23

    Chemokines, a large family of highly versatile small soluble proteins, play crucial roles in defining innate and adaptive immune responses by regulating the trafficking of leukocytes, and also play a key role in various aspects of human physiology. Chemokines share the characteristic feature of reversibly existing as monomers and dimers, and their functional response is intimately coupled to interaction with glycosaminoglycans (GAGs). Currently, nothing is known regarding the structural basis or molecular mechanisms underlying CXCL5-GAG interactions. To address this missing knowledge, we characterized the interaction of a panel of heparin oligosaccharides to CXCL5 using solution NMR, isothermal titration calorimetry, and molecular dynamics simulations. NMR studies indicated that the dimer is the high-affinity GAG binding ligand and that lysine residues from the N-loop, 40s turn, β3 strand, and C-terminal helix mediate binding. Isothermal titration calorimetry indicated a stoichiometry of two oligosaccharides per CXCL5 dimer. NMR-based structural models reveal that these residues form a contiguous surface within a monomer and, interestingly, that the GAG-binding domain overlaps with the receptor-binding domain, indicating that a GAG-bound chemokine cannot activate the receptor. Molecular dynamics simulations indicate that the roles of the individual lysines are not equivalent and that helical lysines play a more prominent role in determining binding geometry and affinity. Further, binding interactions and GAG geometry in CXCL5 are novel and distinctly different compared with the related chemokines CXCL1 and CXCL8. We conclude that a finely tuned balance between the GAG-bound dimer and free soluble monomer regulates CXCL5-mediated receptor signaling and function.

  17. Molecular Basis of Chemokine CXCL5-Glycosaminoglycan Interactions.

    PubMed

    Sepuru, Krishna Mohan; Nagarajan, Balaji; Desai, Umesh R; Rajarathnam, Krishna

    2016-09-23

    Chemokines, a large family of highly versatile small soluble proteins, play crucial roles in defining innate and adaptive immune responses by regulating the trafficking of leukocytes, and also play a key role in various aspects of human physiology. Chemokines share the characteristic feature of reversibly existing as monomers and dimers, and their functional response is intimately coupled to interaction with glycosaminoglycans (GAGs). Currently, nothing is known regarding the structural basis or molecular mechanisms underlying CXCL5-GAG interactions. To address this missing knowledge, we characterized the interaction of a panel of heparin oligosaccharides to CXCL5 using solution NMR, isothermal titration calorimetry, and molecular dynamics simulations. NMR studies indicated that the dimer is the high-affinity GAG binding ligand and that lysine residues from the N-loop, 40s turn, β3 strand, and C-terminal helix mediate binding. Isothermal titration calorimetry indicated a stoichiometry of two oligosaccharides per CXCL5 dimer. NMR-based structural models reveal that these residues form a contiguous surface within a monomer and, interestingly, that the GAG-binding domain overlaps with the receptor-binding domain, indicating that a GAG-bound chemokine cannot activate the receptor. Molecular dynamics simulations indicate that the roles of the individual lysines are not equivalent and that helical lysines play a more prominent role in determining binding geometry and affinity. Further, binding interactions and GAG geometry in CXCL5 are novel and distinctly different compared with the related chemokines CXCL1 and CXCL8. We conclude that a finely tuned balance between the GAG-bound dimer and free soluble monomer regulates CXCL5-mediated receptor signaling and function. PMID:27471273

  18. Evaluating Molecular Interactions in Polycaprolactone-Biomineralized Hydroxyapatite Nanocomposites using Steered Molecular Dynamics

    NASA Astrophysics Data System (ADS)

    Sharma, Anurag; Payne, Scott; Katti, Kalpana S.; Katti, Dinesh R.

    2015-04-01

    An experimental and modeling study of a complex nanoclay-based polymeric scaffold system is presented here. A representative molecular model of polymeric nanocomposite scaffold system for bone tissue engineering applications was developed. Polymeric scaffolds were synthesized using organically modified montmorillonite clay (OMMT) with biomineralized hydroxyapatite and polycaprolactone (OMMT-HAP-PCL). The OMMT-HAP-PCL representative model was constructed and validated using transmission electron microscopy, x-ray diffraction and material density results. We observed strong molecular interactions between OMMT, hydroxyapatite (HAP) and polycaprolactone (PCL) in the OMMT-HAP-PCL system. Attractive and repulsive interactions between PCL and different constituents of OMMT and HAP indicate influence of OMMT-HAP on PCL. Polymeric scaffolds were found to have improved nanomechanical properties as compared to pristine PCL due to the introduction of OMMT-HAP. Stress-strain response for the representative OMMT-HAP-PCL model was evaluated using constant force steered molecular dynamics (SMD) simulations. Two distinct stress-strain responses observed in the system indicate a two-phase nanomechanical behavior of OMMT-HAP-PCL obtained at low and high applied stresses. The results obtained from the MD and SMD simulations provide quantitative understanding of molecular interactions between different constituents of OMMT, HAP and PCL and mechanical response in the OMMT-HAP-PCL system.

  19. Interaction between Cassiopeia A and Nearby Molecular Clouds

    NASA Astrophysics Data System (ADS)

    Kilpatrick, C. D.; Bieging, J. H.; Rieke, G. H.

    2014-12-01

    We present spectroscopy of the supernova remnant Cassiopeia A (Cas A) observed at infrared wavelengths from 10 to 40 μm with the Spitzer Space Telescope and at millimeter wavelengths in 12CO and 13CO J =2-1 (230 and 220 GHz) with the Heinrich Hertz Submillimeter Telescope. The IR spectra demonstrate high-velocity features toward a molecular cloud coincident with a region of bright radio continuum emission along the northern shock front of Cas A. The millimeter observations indicate that CO emission is broadened by a factor of two in some clouds toward Cas A, particularly to the south and west. We believe that these features trace interactions between the Cas A shock front and nearby molecular clouds. In addition, some of the molecular clouds that exhibit broadening in CO lie 1'-2' away from the furthest extent of the supernova remnant shock front. We propose that this material may be accelerated by ejecta with velocity significantly larger than the observed free-expansion velocity of the Cas A shock front. These observations may trace cloud interactions with fast-moving outflows such as the bipolar outflow along the southwest to northeast axis of the Cas A supernova remnant, as well as fast-moving knots seen emerging in other directions.

  20. Interaction between Cassiopeia A and nearby molecular clouds

    SciTech Connect

    Kilpatrick, C. D.; Bieging, J. H.; Rieke, G. H.

    2014-12-01

    We present spectroscopy of the supernova remnant Cassiopeia A (Cas A) observed at infrared wavelengths from 10 to 40 μm with the Spitzer Space Telescope and at millimeter wavelengths in {sup 12}CO and {sup 13}CO J =2-1 (230 and 220 GHz) with the Heinrich Hertz Submillimeter Telescope. The IR spectra demonstrate high-velocity features toward a molecular cloud coincident with a region of bright radio continuum emission along the northern shock front of Cas A. The millimeter observations indicate that CO emission is broadened by a factor of two in some clouds toward Cas A, particularly to the south and west. We believe that these features trace interactions between the Cas A shock front and nearby molecular clouds. In addition, some of the molecular clouds that exhibit broadening in CO lie 1'-2' away from the furthest extent of the supernova remnant shock front. We propose that this material may be accelerated by ejecta with velocity significantly larger than the observed free-expansion velocity of the Cas A shock front. These observations may trace cloud interactions with fast-moving outflows such as the bipolar outflow along the southwest to northeast axis of the Cas A supernova remnant, as well as fast-moving knots seen emerging in other directions.

  1. Interaction of a Julolidine-Based Neutral Ultrafast Molecular Rotor with Natural DNA: Spectroscopic and Molecular Docking Studies.

    PubMed

    Kalel, Rahul; Mora, Aruna K; Ghosh, Rajib; Dhavale, Dilip D; Palit, Dipak K; Nath, Sukhendu

    2016-09-22

    Ultrafast molecular rotors (UMRs) are reported to be one of the best fluorescent sensors to study different microenvironments, including biomolecules. In the present work, we have explored the possibility of application of a julolidine-based neutral UMR, 9-(2,2-dicyano vinyl) julolidine (DCVJ), as a DNA sensor and studied its mode of binding with DNA in detail using spectroscopic and molecular docking techniques. Our spectroscopic studies indicate that association of DCVJ with DNA leads to a very large enhancement in its emission intensity. Detailed investigation reveals that, despite being a neutral molecule, binding of DCVJ with DNA is largely modulated in the presence of salt. Such an unusual salt effect has been explained by invoking the ion-dipole interaction between DCVJ and the phosphate backbone of DNA. The ion-dipole interaction has also been established by studying the interaction of DCVJ with nucleosides. Detailed time-resolved studies show that the twisting motion around the vinyl bond in DCVJ gets retarded to a great extent because of its association with DNA molecules. Through competitive binding studies, it has also been established that DCVJ also binds to DNA through intercalation. Finally, quantum chemical calculations and molecular docking studies have been performed to confirm the mode of binding of DCVJ with DNA. PMID:27559832

  2. Unravelling Protein-DNA Interactions at Molecular Level: A DFT and NCI Study.

    PubMed

    González, J; Baños, I; León, I; Contreras-García, J; Cocinero, E J; Lesarri, A; Fernández, J A; Millán, J

    2016-02-01

    Histone-DNA interactions were probed computationally at a molecular level, by characterizing the bimolecular clusters constituted by selected amino acid derivatives with polar (asparagine and glutamine), nonpolar (alanine, valine, and isoleucine), and charged (arginine) side chains and methylated pyrimidinic (1-methylcytosine and 1-methylthymine) and puric (9-methyladenine and 9-methylguanine) DNA bases. The computational approach combined different methodologies: a molecular mechanics (MMFFs forced field) conformational search and structural and vibrational density-functional calculations (M06-2X with double and triple-ζ Pople's basis sets). To dissect the interactions, intermolecular forces were analyzed with the Non-Covalent Interactions (NCI) analysis. The results for the 24 different clusters studied show a noticeable correlation between the calculated binding energies and the propensities for protein-DNA base interactions found in the literature. Such correlation holded even for the interaction of the selected amino acid derivatives with Watson and Crick pairs. Therefore, the balance between hydrogen bonds and van der Waals interactions (specially stacking) in the control of the final shape of the investigated amino acid-DNA base pairs seems to be well reproduced in dispersion-corrected DFT molecular models, reinforcing the idea that the specificity between the amino acids and the DNA bases play an important role in the regulation of DNA. PMID:26765058

  3. Investigation on the interaction of letrozole with herring sperm DNA through spectroscopic and modeling methods.

    PubMed

    Huang, Yan-Mei; Zheng, Shou-Jun; Yan, Jin; Yang, Hong-Qin; Wu, Di; Wang, Qing; Li, Hui

    2016-08-01

    The interaction of letrozole, an efficient and safe aromatase inhibitor, with herring sperm DNA (hsDNA) was investigated in vitro through spectroscopy analysis and molecular modeling to elucidate the binding mechanism of anticancer drugs and DNA. The binding constant and the number of binding sites were 2.13 × 10(4)  M(-1) and 1.09, respectively, at 298 K. Thermodynamic parameters (ΔG, ΔH and ΔS) exhibited negative values, which indicated that binding was spontaneous and Van der Waals forces and hydrogen bond were the main interaction forces. Fourier transform infrared spectroscopy and other spectroscopy analysis methods illustrated that letrozole could intercalate into the phosphate backbone of hsDNA and interact with the nitrogenous bases. Consistent with the experimental findings, molecular modeling results demonstrated that the interaction was dominated by intercalation and hydrogen bonding. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26669513

  4. Investigation on the interaction of letrozole with herring sperm DNA through spectroscopic and modeling methods.

    PubMed

    Huang, Yan-Mei; Zheng, Shou-Jun; Yan, Jin; Yang, Hong-Qin; Wu, Di; Wang, Qing; Li, Hui

    2016-08-01

    The interaction of letrozole, an efficient and safe aromatase inhibitor, with herring sperm DNA (hsDNA) was investigated in vitro through spectroscopy analysis and molecular modeling to elucidate the binding mechanism of anticancer drugs and DNA. The binding constant and the number of binding sites were 2.13 × 10(4)  M(-1) and 1.09, respectively, at 298 K. Thermodynamic parameters (ΔG, ΔH and ΔS) exhibited negative values, which indicated that binding was spontaneous and Van der Waals forces and hydrogen bond were the main interaction forces. Fourier transform infrared spectroscopy and other spectroscopy analysis methods illustrated that letrozole could intercalate into the phosphate backbone of hsDNA and interact with the nitrogenous bases. Consistent with the experimental findings, molecular modeling results demonstrated that the interaction was dominated by intercalation and hydrogen bonding. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Probing Interactions in Complex Molecular Systems through Ordered Assembly

    SciTech Connect

    De Yoreo, J J; Bartelt, M C; Orme, C A; Villacampa, A; Weeks, B L; Miller, A E

    2002-01-31

    Emerging from the machinery of epitaxial science and chemical synthesis, is a growing emphasis on development of self-organized systems of complex molecular species. The nature of self-organization in these systems spans the continuum from simple crystallization of large molecules such as dendrimers and proteins, to assembly into large organized networks of nanometer-scale structures such as quantum dots or nanoparticles. In truth, self-organization in complex molecular systems has always been a central feature of many scientific disciplines including fields as diverse as structural biology, polymer science and geochemistry. But over the past decade, changes in those fields have often been marked by the degree to which researchers are using molecular-scale approaches to understand the hierarchy of structures and processes driven by this ordered assembly. At the same time, physical scientists have begun to use their knowledge of simple atomic and molecular systems to fabricate synthetic self-organized systems. This increasing activity in the field of self-organization is testament to the success of the physical and chemical sciences in building a detailed understanding of crystallization and epitaxy in simple atomic and molecular systems, one that is soundly rooted in thermodynamics and chemical kinetics. One of the fundamental challenges of chemistry and materials science in the coming decades is to develop a similarly well-founded physical understanding of assembly processes in complex molecular systems. Over the past five years, we have successfully used in situ atomic force microscopy (AFM) to investigate the physical controls on single crystal epitaxy from solutions for a wide range of molecular species. More recently, we have combined this method with grazing incidence X-ray diffraction and kinetic Monte Carlo modeling in order to relate morphology to surface atomic structure and processes. The purpose of this proposal was to extend this approach to assemblies

  6. Electron-phonon interaction within classical molecular dynamics

    DOE PAGESBeta

    Tamm, A.; Samolyuk, G.; Correa, A. A.; Klintenberg, M.; Aabloo, A.; Caro, A.

    2016-07-14

    Here, we present a model for nonadiabatic classical molecular dynamics simulations that captures with high accuracy the wave-vector q dependence of the phonon lifetimes, in agreement with quantum mechanics calculations. It is based on a local view of the e-ph interaction where individual atom dynamics couples to electrons via a damping term that is obtained as the low-velocity limit of the stopping power of a moving ion in a host. The model is parameter free, as its components are derived from ab initio-type calculations, is readily extended to the case of alloys, and is adequate for large-scale molecular dynamics computermore » simulations. We also show how this model removes some oversimplifications of the traditional ionic damped dynamics commonly used to describe situations beyond the Born-Oppenheimer approximation.« less

  7. [Molecular mechanisms of the plague pathogenic agent interaction with invertebrates].

    PubMed

    Kutyrev, V V; Eroshenko, G A; Popov, N V; Vidiaeva, N A; Konnov, N P

    2009-01-01

    Microbe Russian Anti-Plague Research Institute, Saratov, Russia The literature data and experimental results of the authors on the molecular basis of plague agent interaction with invertebrates are discussed. The details of the plague agent life cycle, its genome organization, and molecular genetic mechanisms of its survival in flea vector and on the nematode cuticule are discussed. The experimental data about the ability to form biofilms at abiotic and biotic surfaces in the Yersinia pestis strains of the main and non-main subspecies are presented. Mechanisms of horizontal and vertical transmission of plague agent are considered. The suggestion about participation of the new member in the complex parasitic biocenosis (nematode, vector parasite) is put forward. PMID:20050160

  8. Electron-phonon interaction within classical molecular dynamics

    NASA Astrophysics Data System (ADS)

    Tamm, A.; Samolyuk, G.; Correa, A. A.; Klintenberg, M.; Aabloo, A.; Caro, A.

    2016-07-01

    We present a model for nonadiabatic classical molecular dynamics simulations that captures with high accuracy the wave-vector q dependence of the phonon lifetimes, in agreement with quantum mechanics calculations. It is based on a local view of the e -ph interaction where individual atom dynamics couples to electrons via a damping term that is obtained as the low-velocity limit of the stopping power of a moving ion in a host. The model is parameter free, as its components are derived from ab initio-type calculations, is readily extended to the case of alloys, and is adequate for large-scale molecular dynamics computer simulations. We also show how this model removes some oversimplifications of the traditional ionic damped dynamics commonly used to describe situations beyond the Born-Oppenheimer approximation.

  9. Ab Initio Study of Molecular Interactions in Cellulose Iα

    SciTech Connect

    Devarajan, Ajitha; Markutsya, Serjiy; Lamm, Monica H.; Cheng, Xiaolin; Smith, Jeremy C.; Baluyut, John Y.; Kholod, Yana; Gordon, Mark S.; Windus, Theresa L.

    2013-08-12

    Biomass recalcitrance, the resistance of cellulosic biomass to degradation, is due in part to the stability of the hydrogen bond network and stacking forces between the polysaccharide chains in cellulose microfibers. The fragment molecular orbital (FMO) method at the correlated Møller–Plesset second order perturbation level of theory was used on a model of the crystalline cellulose Iα core with a total of 144 glucose units. These computations show that the intersheet chain interactions are stronger than the intrasheet chain interactions for the crystalline structure, while they are more similar to each other for a relaxed structure. An FMO chain pair interaction energy decomposition analysis for both the crystal and relaxed structures reveals an intricate interplay between electrostatic, dispersion, charge transfer, and exchange repulsion effects. The role of the primary alcohol groups in stabilizing the interchain hydrogen bond network in the inner sheet of the crystal and relaxed structures of cellulose Iα, where edge effects are absent, was analyzed. The maximum attractive intrasheet interaction is observed for the GT-TG residue pair with one intrasheet hydrogen bond, suggesting that the relative orientation of the residues is as important as the hydrogen bond network in strengthening the interaction between the residues.

  10. [Evolution and systematics of nematodes based on molecular investigation].

    PubMed

    Okulewicz, Anna; Perec, Agnieszka

    2004-01-01

    Evolution and systematics of nematodes based on molecular investigation. The use of molecular phylogenetics to examine the interrelationships between animal parasites, free-living nematodes, and plant parasites versus traditional classification based on morphological-ecological characters was discussed and reviewed. Distinct differences were observed between parasitic nematodes and free-living ones. Within the former group, animal parasites turned out to be distinctly different from plant parasites. Using small subunit of ribosomal RNA gene sequence from a wide range of nematodes, there is a possibility to compare animal-parasitic, plant-parasitic and free-living taxa. Nowadays the parasitic nematodes expressed sequence tag (EST) project is currently generating sequence information to provide a new source of data to examine the evolutionary history of this taxonomic group. PMID:16859012

  11. Shock induced phase transition of water: Molecular dynamics investigation

    NASA Astrophysics Data System (ADS)

    Neogi, Anupam; Mitra, Nilanjan

    2016-02-01

    Molecular dynamics simulations were carried out using numerous force potentials to investigate the shock induced phenomenon of pure bulk liquid water. Partial phase transition was observed at single shock velocity of 4.0 km/s without requirement of any external nucleators. Change in thermodynamic variables along with radial distribution function plots and spectral analysis revealed for the first time in the literature, within the context of molecular dynamic simulations, the thermodynamic pathway leading to formation of ice VII from liquid water on shock loading. The study also revealed information for the first time in the literature about the statistical time-frame after passage of shock in which ice VII formation can be observed and variations in degree of crystallinity of the sample over the entire simulation time of 100 ns.

  12. Comparison between Free and Immobilized Ion Effects on Hydrophobic Interactions: A Molecular Dynamics Study.

    PubMed

    Huang, Kai; Gast, Sebastian; Ma, C Derek; Abbott, Nicholas L; Szlufarska, Izabela

    2015-10-15

    Fundamental studies of the effect of specific ions on hydrophobic interactions are driven by the need to understand phenomena such as hydrophobically driven self-assembly or protein folding. Using β-peptide-inspired nanorods, we investigate the effects of both free ions (dissolved salts) and proximally immobilized ions on hydrophobic interactions. We find that the free ion effect is correlated with the water density fluctuation near a nonpolar molecular surface, showing that such fluctuation can be an indicator of hydrophobic interactions in the case of solution additives. In the case of immobilized ion, our results demonstrate that hydrophobic interactions can be switched on and off by choosing different spatial arrangements of proximal ions on a nanorod. For globally amphiphilic nanorods, we find that the magnitude of the interaction can be further tuned using proximal ions with varying ionic sizes. In general, univalent proximal anions are found to weaken hydrophobic interactions. This is in contrast to the effect of free ions, which according to our simulations strengthen hydrophobic interactions. In addition, immobilized anions of increasing ionic size do not follow the same ordering (Hofmeister-like ranking) as free ions when it comes to their impact on hydrophobic interactions. The immobilized ion effect is not simply correlated with the water density fluctuation near the nonpolar side of the amphiphilic nanorod. We propose a molecular picture that explains the contrasting effects of immobilized versus free ions.

  13. Evaluation of molecular methods used for establishing the interactions and functions of microorganisms in anaerobic bioreactors.

    PubMed

    Talbot, G; Topp, E; Palin, M F; Massé, D I

    2008-02-01

    Molecular techniques have unveiled the complexity of the microbial consortium in anaerobic bioreactors and revealed the presence of several uncultivated species. This paper presents a review of the panoply of classical and recent molecular approaches and multivariate analyses that have been, or might be used to establish the interactions and functions of these anaerobic microorganisms. Most of the molecular approaches used so far are based on the analysis of small subunit ribosomal RNA but recent studies also use quantification of functional gene expressions. There are now several studies that have developed quantitative real-time PCR assays to investigate methanogens. With a view to improving the stability and performance of bioreactors, monitoring with molecular methods is also discussed. Advances in metagenomics and proteomics will lead to the development of promising lab-on chip technologies for cost-effective monitoring.

  14. Investigation of glassy state molecular motions in thermoset polymers

    NASA Astrophysics Data System (ADS)

    Tu, Jianwei

    This dissertation presents the investigation of the glassy state molecular motions in isomeric thermoset epoxies by means of solid-state deuterium (2H) NMR spectroscopy technique. The network structure of crosslinked epoxies was altered through monomer isomerism; specifically, diglycidyl ether of bisphenol A (DGEBA) was cured with isomeric amine curatives, i.e., the meta-substituted diaminodiphenylsulfone (33DDS) and para-substituted diaminodiphenylsulfone (44DDS). The use of structural isomerism provided a path way for altering macroscopic material properties while maintaining identical chemical composition within the crosslinked networks. The effects of structural isomerism on the glassy state molecular motions were studied using solid-state 2H NMR spectroscopy, which offers unrivaled power to monitor site-specific molecular motions. Three distinctive molecular groups on each isomeric network, i.e., the phenylene rings in the bisphenol A structure (BPA), the phenylene rings in the diaminodiphenylsulfone structure (DDS), and the hydroxypropoyl ether group (HPE) have been selectively deuterated for a comprehensive study of the structure-dynamics- property relationships in thermoset epoxies. Quadrupolar echo experiments and line shape simulations were employed as the main research approach to gain both qualitative and quantitative motional information of the epoxy networks in the glassy state. Quantitative information on the geometry and rate of the molecular motions allows the elucidation of the relationship between molecular motions and macro physical properties and the role of these motions in the mechanical relaxation. Specifically, it is revealed that both the BPA and HPE moieties in the isomeric networks have almost identical behaviors in the deep glassy state, which indicates that the molecular motions in the glassy state are localized, and the correlation length of the motions does not exceed the length of the DGEBA repeat unit. BPA ring motions contribute

  15. MOLVIE: an interactive visualization environment for molecular structures.

    PubMed

    Sun, Huandong; Li, Ming; Xu, Ying

    2003-05-01

    A Molecular visualization interactive environment (MOLVIE), is designed to display three-dimensional (3D) structures of molecules and support the structural analysis and research on proteins. The paper presents the features, design considerations and applications of MOLVIE, especially the new functions used to compare the structures of two molecules and view the partial fragment of a molecule. Being developed in JAVA, MOLVIE is platform-independent. Moreover, it may run on a webpage as an applet for remote users. MOLVIE is available at http://www.cs.ucsb.edu/~mli/Bioinf/software/index.html. PMID:12725967

  16. Characterization of the Interaction between Gallic Acid and Lysozyme by Molecular Dynamics Simulation and Optical Spectroscopy.

    PubMed

    Zhan, Minzhong; Guo, Ming; Jiang, Yanke; Wang, Xiaomeng

    2015-07-01

    The binding interaction between gallic acid (GA) and lysozyme (LYS) was investigated and compared by molecular dynamics (MD) simulation and spectral techniques. The results from spectroscopy indicate that GA binds to LYS to generate a static complex. The binding constants and thermodynamic parameters were calculated. MD simulation revealed that the main driving forces for GA binding to LYS are hydrogen bonding and hydrophobic interactions. The root-mean-square deviation verified that GA and LYS bind to form a stable complex, while the root-mean-square fluctuation results showed that the stability of the GA-LYS complex at 298 K was higher than that at 310 K. The calculated free binding energies from the molecular mechanics/Poisson-Boltzmann surface area method showed that van der Waals forces and electrostatic interactions are the predominant intermolecular forces. The MD simulation was consistent with the spectral experiments. This study provides a reference for future study of the pharmacological mechanism of GA.

  17. Transient Induced Molecular Electronic Spectroscopy (TIMES) for study of protein-ligand interactions

    PubMed Central

    Zhang, Tiantian; Ku, Ti-Hsuan; Han, Yuanyuan; Subramanian, Ramkumar; Niaz, Iftikhar Ahmad; Luo, Hua; Chang, Derrick; Huang, Jian-Jang; Lo, Yu-Hwa

    2016-01-01

    We present a method, Transient Induced Molecular Electronic Spectroscopy (TIMES), to detect protein-ligand interactions without any protein engineering or chemical modification. We developed a physics model for the TIMES signal and mathematically formulated the problem to attain physical insight of protein-ligand interactions without any disturbances by molecular probes, fluorescent labels, or immobilization of molecules. To demonstrate the functionality of this method, we have used the TIMES signals to find the dissociation constants for the affinity of reactions, the shear-stress dependent adsorption time of molecules on surface, and other interesting features of protein-ligand interaction in native conditions. As a unique tool, TIMES offers a simple and effective method to investigate fundamental protein chemistry and drug discoveries. PMID:27759045

  18. Diffusion and separation of CH4/N2 in pillared graphene nanomaterials: A molecular dynamics investigation

    NASA Astrophysics Data System (ADS)

    Zhou, Sainan; Lu, Xiaoqing; Wu, Zhonghua; Jin, Dongliang; Guo, Chen; Wang, Maohuai; Wei, Shuxian

    2016-09-01

    Diffusion and separation of CH4/N2 in pillared graphene were investigated by molecular dynamics. The pillared graphene with (6, 6) carbon nanotube (CNT) exhibited the higher diffusion and selectivity of CH4 over N2 than that with (7, 7) CNT due to the cooperative effect of pore topological characteristics and interaction energy. The stronger interaction facilitated CH4 to enter CNT prior to N2, and higher pressure promoted CH4 to pass CNT more easily. The relative concentrations profiles showed that CH4 reached equilibrium state faster than N2 at low pressure. Our results highlight potential use of pillared graphene in gas purification and separation.

  19. Molecular Insights into the Potential Toxicological Interaction of 2-Mercaptothiazoline with the Antioxidant Enzyme—Catalase

    PubMed Central

    Huang, Zhenxing; Huang, Ming; Mi, Chenyu; Wang, Tao; Chen, Dong; Teng, Yue

    2016-01-01

    2-mercaptothiazoline (2-MT) is widely used in many industrial fields, but its residue is potentially harmful to the environment. In this study, to evaluate the biological toxicity of 2-MT at protein level, the interaction between 2-MT and the pivotal antioxidant enzyme—catalase (CAT) was investigated using multiple spectroscopic techniques and molecular modeling. The results indicated that the CAT fluorescence quenching caused by 2-MT should be dominated by a static quenching mechanism through formation of a 2-MT/CAT complex. Furthermore, the identifications of the binding constant, binding forces, and the number of binding sites demonstrated that 2-MT could spontaneously interact with CAT at one binding site mainly via Van der Waals’ forces and hydrogen bonding. Based on the molecular docking simulation and conformation dynamic characterization, it was found that 2-MT could bind into the junctional region of CAT subdomains and that the binding site was close to enzyme active sites, which induced secondary structural and micro-environmental changes in CAT. The experiments on 2-MT toxicity verified that 2-MT significantly inhibited CAT activity via its molecular interaction, where 2-MT concentration and exposure time both affected the inhibitory action. Therefore, the present investigation provides useful information for understanding the toxicological mechanism of 2-MT at the molecular level. PMID:27537873

  20. Molecular Insights into the Potential Toxicological Interaction of 2-Mercaptothiazoline with the Antioxidant Enzyme-Catalase.

    PubMed

    Huang, Zhenxing; Huang, Ming; Mi, Chenyu; Wang, Tao; Chen, Dong; Teng, Yue

    2016-01-01

    2-mercaptothiazoline (2-MT) is widely used in many industrial fields, but its residue is potentially harmful to the environment. In this study, to evaluate the biological toxicity of 2-MT at protein level, the interaction between 2-MT and the pivotal antioxidant enzyme-catalase (CAT) was investigated using multiple spectroscopic techniques and molecular modeling. The results indicated that the CAT fluorescence quenching caused by 2-MT should be dominated by a static quenching mechanism through formation of a 2-MT/CAT complex. Furthermore, the identifications of the binding constant, binding forces, and the number of binding sites demonstrated that 2-MT could spontaneously interact with CAT at one binding site mainly via Van der Waals' forces and hydrogen bonding. Based on the molecular docking simulation and conformation dynamic characterization, it was found that 2-MT could bind into the junctional region of CAT subdomains and that the binding site was close to enzyme active sites, which induced secondary structural and micro-environmental changes in CAT. The experiments on 2-MT toxicity verified that 2-MT significantly inhibited CAT activity via its molecular interaction, where 2-MT concentration and exposure time both affected the inhibitory action. Therefore, the present investigation provides useful information for understanding the toxicological mechanism of 2-MT at the molecular level. PMID:27537873

  1. Molecular dynamics modeling of a nanomaterials-water surface interaction

    NASA Astrophysics Data System (ADS)

    Nejat Pishkenari, Hossein; Keramati, Ramtin; Abdi, Ahmad; Minary-Jolandan, Majid

    2016-04-01

    In this article, we study the formation of nanomeniscus around a nanoneedle using molecular dynamics simulation approach. The results reveal three distinct phases in the time-evolution of meniscus before equilibrium according to the contact angle, meniscus height, and potential energy. In addition, we investigated the correlation between the nanoneedle diameter and nanomeniscus characteristics. The results have applications in various fields such as scanning probe microscopy and rheological measurements.

  2. Density functional theory based study of molecular interactions, recognition, engineering, and quantum transport in π molecular systems.

    PubMed

    Cho, Yeonchoo; Cho, Woo Jong; Youn, Il Seung; Lee, Geunsik; Singh, N Jiten; Kim, Kwang S

    2014-11-18

    CONSPECTUS: In chemical and biological systems, various interactions that govern the chemical and physical properties of molecules, assembling phenomena, and electronic transport properties compete and control the microscopic structure of materials. The well-controlled manipulation of each component can allow researchers to design receptors or sensors, new molecular architectures, structures with novel morphology, and functional molecules or devices. In this Account, we describe the structures and electronic and spintronic properties of π-molecular systems that are important for controlling the architecture of a variety of carbon-based systems. Although DFT is an important tool for describing molecular interactions, the inability of DFT to accurately represent dispersion interactions has made it difficult to properly describe π-interactions. However, the recently developed dispersion corrections for DFT have allowed us to include these dispersion interactions cost-effectively. We have investigated noncovalent interactions of various π-systems including aromatic-π, aliphatic-π, and non-π systems based on dispersion-corrected DFT (DFT-D). In addition, we have addressed the validity of DFT-D compared with the complete basis set (CBS) limit values of coupled cluster theory with single, double, and perturbative triple excitations [CCSD(T)] and Møller-Plesset second order perturbation theory (MP2). The DFT-D methods are still unable to predict the correct ordering in binding energies within the benzene dimer and the cyclohexane dimer. Nevertheless, the overall DFT-D predicted binding energies are in reasonable agreement with the CCSD(T) results. In most cases, results using the B97-D3 method closely reproduce the CCSD(T) results with the optimized energy-fitting parameters. On the other hand, vdW-DF2 and PBE0-TS methods estimate the dispersion energies from the calculated electron density. In these approximations, the interaction energies around the equilibrium

  3. An Investigation of Molecular Docking and Molecular Dynamic Simulation on Imidazopyridines as B-Raf Kinase Inhibitors.

    PubMed

    Xie, Huiding; Li, Yupeng; Yu, Fang; Xie, Xiaoguang; Qiu, Kaixiong; Fu, Jijun

    2015-11-16

    In the recent cancer treatment, B-Raf kinase is one of key targets. Nowadays, a group of imidazopyridines as B-Raf kinase inhibitors have been reported. In order to investigate the interaction between this group of inhibitors and B-Raf kinase, molecular docking, molecular dynamic (MD) simulation and binding free energy (ΔGbind) calculation were performed in this work. Molecular docking was carried out to identify the key residues in the binding site, and MD simulations were performed to determine the detail binding mode. The results obtained from MD simulation reveal that the binding site is stable during the MD simulations, and some hydrogen bonds (H-bonds) in MD simulations are different from H-bonds in the docking mode. Based on the obtained MD trajectories, ΔGbind was computed by using Molecular Mechanics Generalized Born Surface Area (MM-GBSA), and the obtained energies are consistent with the activities. An energetic analysis reveals that both electrostatic and van der Waals contributions are important to ΔGbind, and the unfavorable polar solvation contribution results in the instability of the inhibitor with the lowest activity. These results are expected to understand the binding between B-Raf and imidazopyridines and provide some useful information to design potential B-Raf inhibitors.

  4. Interaction of peptides with cell membranes: insights from molecular modeling

    NASA Astrophysics Data System (ADS)

    Li, Zhen-lu; Ding, Hong-ming; Ma, Yu-qiang

    2016-03-01

    The investigation of the interaction of peptides with cell membranes is the focus of active research. It can enhance the understanding of basic membrane functions such as membrane transport, fusion, and signaling processes, and it may shed light on potential applications of peptides in biomedicine. In this review, we will present current advances in computational studies on the interaction of different types of peptides with the cell membrane. Depending on the properties of the peptide, membrane, and external environment, the peptide-membrane interaction shows a variety of different forms. Here, on the basis of recent computational progress, we will discuss how different peptides could initiate membrane pores, translocate across the membrane, induce membrane endocytosis, produce membrane curvature, form fibrils on the membrane surface, as well as interact with functional membrane proteins. Finally, we will present a conclusion summarizing recent progress and providing some specific insights into future developments in this field.

  5. Nonlinear Optical Investigations of Vibrational Relaxation in Molecular Crystals

    NASA Astrophysics Data System (ADS)

    Decola, Philip Lawrence

    Experimental studies of four-wave mixing have been used to obtain novel spectroscopic information in molecular crystals. This work can be separated into singly resonant and multiresonant investigations. One effort was to exploit the frequency and time domain capabilities of singly resonant coherent anti-Stokes Raman spectroscopy (CARS) to study vibrational dynamics in naphthalene and benzene single crystals at liquid Helium temperatures. To a large extent vibrational energy is chemical energy, so to understand the flow of vibrational energy in molecules and molecular aggregates can enhance our understanding of chemical reaction rates and pathways. Some of the salient results are: (1) the existence of motional narrowing in molecular crystals makes it possible for lifetime (T _1) broadening to dominate the linewidth of the vibrational transition even when the intrinsic disorder width is much larger than 1/T_1, (2) relaxation in molecular crystals can be surprisingly slow, ranging from subnanosecond to nanosecond, (3) substantial mode dependent contribution to relaxation from ^{13}C impurities in benzene, and (4) evidence of mode specific energy relaxation observed in a systematic study of benzene Raman active modes. The results obtained here are applied to the problems of understanding the contributions to residual low-temperature vibron linewidths and of developing simple mechanical intuitions to explain systematically the kinetic pathways for vibrational relaxation in molecular crystals. These results are discussed in light of the current theories of excitation dynamics in condensed phases. The other area of study was multiresonant nonlinear spectroscopic investigations of mixed organic crystals. The first multiresonant CARS and its Stokes analogue (CSRS) have been obtained in a mixed crystal of pentacene in benzoic acid allowing the simultaneous observation of ground and excited state Raman spectra. These spectra contain lines that are much sharper than expected

  6. A microcalorimetric study of molecular interactions between immunoglobulin G and hydrophobic charge-induction ligand.

    PubMed

    Yuan, Xiao-Ming; Lin, Dong-Qiang; Zhang, Qi-Lei; Gao, Dong; Yao, Shan-Jing

    2016-04-22

    Hydrophobic charge-induction chromatography (HCIC) with 4-mercaptoethyl-pyridine (MEP) as the ligand is a novel technology for antibody purification. In this study, isothermal titration calorimetry (ITC) was used to evaluate the molecular interactions between MEP ligand and immunoglobulin G (IgG). Three types of IgG molecules including human IgG (hIgG), bovine IgG (bIgG) and a monoclonal antibody (mAb) were investigated with human serum albumins (HSA) and bovine serum albumin (BSA) as the comparison. The thermodynamic parameters obtained from ITC were compared with the adsorption data. The results indicated that MEP binding to protein at neutral pH was entropy driven and induced by multimodal molecular interactions that was dominated by hydrophobic forces. The interactions between MEP and IgGs were stronger than that of albumins, which resulted in high binding affinity of IgGs. Moreover, the effects of pH and salt addition on MEP-hIgG binding were studied. The change of enthalpy increased obviously with the decrease of pH, which revealed that the electrostatic forces dominated the MEP-hIgG interactions at acidic condition and caused typical charge-induced elution of HCIC. Salt addition influenced both hydrophobic and electrostatic interactions. With the increase of salt concentration, the hydrophobic interactions decreased first and then increased, while the electrostatic interactions showed the opposite trend. This resulted in trade-off between the multimodal interactions, which caused the salt-tolerant property of MEP resin. In general, ITC studies revealed the molecular mechanism of three critical characteristics of HCIC, multimodal interactions, pH-dependent and salt-tolerant properties.

  7. A microcalorimetric study of molecular interactions between immunoglobulin G and hydrophobic charge-induction ligand.

    PubMed

    Yuan, Xiao-Ming; Lin, Dong-Qiang; Zhang, Qi-Lei; Gao, Dong; Yao, Shan-Jing

    2016-04-22

    Hydrophobic charge-induction chromatography (HCIC) with 4-mercaptoethyl-pyridine (MEP) as the ligand is a novel technology for antibody purification. In this study, isothermal titration calorimetry (ITC) was used to evaluate the molecular interactions between MEP ligand and immunoglobulin G (IgG). Three types of IgG molecules including human IgG (hIgG), bovine IgG (bIgG) and a monoclonal antibody (mAb) were investigated with human serum albumins (HSA) and bovine serum albumin (BSA) as the comparison. The thermodynamic parameters obtained from ITC were compared with the adsorption data. The results indicated that MEP binding to protein at neutral pH was entropy driven and induced by multimodal molecular interactions that was dominated by hydrophobic forces. The interactions between MEP and IgGs were stronger than that of albumins, which resulted in high binding affinity of IgGs. Moreover, the effects of pH and salt addition on MEP-hIgG binding were studied. The change of enthalpy increased obviously with the decrease of pH, which revealed that the electrostatic forces dominated the MEP-hIgG interactions at acidic condition and caused typical charge-induced elution of HCIC. Salt addition influenced both hydrophobic and electrostatic interactions. With the increase of salt concentration, the hydrophobic interactions decreased first and then increased, while the electrostatic interactions showed the opposite trend. This resulted in trade-off between the multimodal interactions, which caused the salt-tolerant property of MEP resin. In general, ITC studies revealed the molecular mechanism of three critical characteristics of HCIC, multimodal interactions, pH-dependent and salt-tolerant properties. PMID:27017449

  8. Targeting molecular interactions essential for Plasmodium sexual reproduction

    PubMed Central

    Vega-Rodriguez, Joel; Perez-Barreto, Davinia; Ruiz-Reyes, Antonio; Jacobs-Lorena, Marcelo

    2015-01-01

    Summary Malaria remains one of the most devastating infectious diseases, killing up to a million people every year. Whereas much progress has been made in understanding the life cycle of the parasite in the human host and in the mosquito vector, significant gaps of knowledge remain. Fertilization of malaria parasites, a process that takes place in the lumen of the mosquito midgut, is poorly understood and the molecular interactions (receptor–ligand) required for Plasmodium fertilization remain elusive. By use of a phage display library, we identified FG1 (Female Gamete peptide 1), a peptide that binds specifically to the surface of female Plasmodium berghei gametes. Importantly, FG1 but not a scrambled version of the peptide, strongly reduces P. berghei oocyst formation by interfering with fertilization. In addition, FG1 also inhibits P. falciparum oocyst formation suggesting that the peptide binds to a molecule on the surface of the female gamete whose structure is conserved. Identification of the molecular interactions disrupted by the FG1 peptide may lead to the development of novel malaria transmission-blocking strategies. PMID:25944054

  9. A molecular model for H(2) interactions in aliphatic and aromatic hydrocarbons.

    PubMed

    Figueroa-Gerstenmaier, Susana; Giudice, Simona; Cavallo, Luigi; Milano, Giuseppe

    2009-05-28

    A model for molecular hydrogen interacting with aliphatic and aromatic hydrocarbons is presented. The model has been derived using ab initio techniques and molecular dynamics simulations. In particular, quadrupole moments of hydrogen, and variation on energy with intermolecular distance of different conformations for the hydrogen-benzene couple were calculated using the Møller-Plesset method. Hydrogen was modelled using a two-centre Lennard-Jones potential plus electrostatic interactions. Lennard-Jones parameters were optimized on the basis of a correct reproduction of experimental data of hydrogen solubility in benzene and cyclohexane, calculated using the test particle insertion method. Different sets of parameters for specific interactions (hydrogen-aliphatic and hydrogen-aromatic systems) were considered avoiding the simple use of Lorentz-Berthelot combining rules. Additionally, structural and thermodynamic properties of hydrogen-benzene, hydrogen-cyclohexane and hydrogen in an equimolar mixture of benzene-cyclohexane at different low concentrations of hydrogen were investigated by means of molecular dynamics simulations. Electrostatic charges were taken from ab initio quantum mechanical calculations but after careful analysis of the calculated properties, their irrelevance was evidenced. Moreover, Coulombic interactions make simulations more expensive and, therefore, we do not recommend their inclusion in the modelling of hydrogen-aliphatic and aromatic interactions. PMID:19440622

  10. Depositions of molecular nanomagnets on graphene investigated with atomic force microscopy and Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Walker, Sean; Vojvodin, Cameron; Li, Zhi; Willick, Kyle; Tang, Xiaowu (Shirley); Baugh, Jonathan

    Molecular nanomagnets display interesting quantum phenomena, and have been proposed as potential building blocks in a variety of nanoelectronic devices with applications to both quantum memory and quantum information processing. These devices often require deposition of the molecules either sparsely (e.g. for single molecule devices) or as a thin-film. Consequently, in order for these devices to be successfully realized, the nature of the interactions between nanomagnets and the surfaces on which they may be deposited needs to be understood. We have investigated the depositions of molecular nanomagnets on graphene using atomic force microscopy and Raman spectrocopy. The nanomagnets contained a range of chemical functional groups including long alkyl chains and extended π-systems of electrons. By comparing their binding affinities we learn about the nature of the interactions between the different functional groups and the graphene.

  11. Deconvolving molecular signatures of interactions between microbial colonies

    PubMed Central

    Harn, Y.-C.; Powers, M. J.; Shank, E. A.; Jojic, V.

    2015-01-01

    Motivation: The interactions between microbial colonies through chemical signaling are not well understood. A microbial colony can use different molecules to inhibit or accelerate the growth of other colonies. A better understanding of the molecules involved in these interactions could lead to advancements in health and medicine. Imaging mass spectrometry (IMS) applied to co-cultured microbial communities aims to capture the spatial characteristics of the colonies’ molecular fingerprints. These data are high-dimensional and require computational analysis methods to interpret. Results: Here, we present a dictionary learning method that deconvolves spectra of different molecules from IMS data. We call this method MOLecular Dictionary Learning (MOLDL). Unlike standard dictionary learning methods which assume Gaussian-distributed data, our method uses the Poisson distribution to capture the count nature of the mass spectrometry data. Also, our method incorporates universally applicable information on common ion types of molecules in MALDI mass spectrometry. This greatly reduces model parameterization and increases deconvolution accuracy by eliminating spurious solutions. Moreover, our method leverages the spatial nature of IMS data by assuming that nearby locations share similar abundances, thus avoiding overfitting to noise. Tests on simulated datasets show that this method has good performance in recovering molecule dictionaries. We also tested our method on real data measured on a microbial community composed of two species. We confirmed through follow-up validation experiments that our method recovered true and complete signatures of molecules. These results indicate that our method can discover molecules in IMS data reliably, and hence can help advance the study of interaction of microbial colonies. Availability and implementation: The code used in this paper is available at: https://github.com/frizfealer/IMS_project. Contact: vjojic@cs.unc.edu Supplementary

  12. Molecular recognition of malachite green by hemoglobin and their specific interactions: insights from in silico docking and molecular spectroscopy.

    PubMed

    Peng, Wei; Ding, Fei; Peng, Yu-Kui; Sun, Ying

    2014-01-01

    Malachite green is an organic compound that can be widely used as a dyestuff for various materials; it has also emerged as a controversial agent in aquaculture. Since malachite green is proven to be carcinogenic and mutagenic, it may become a hazard to public health. For this reason, it is urgently required to analyze this controversial dye in more detail. In our current research, the interaction between malachite green and hemoglobin under physiological conditions was investigated by the methods of molecular modeling, fluorescence spectroscopy, circular dichroism (CD) as well as hydrophobic ANS displacement experiments. From the molecular docking, the central cavity of hemoglobin was assigned to possess high-affinity for malachite green, this result was corroborated by time-resolved fluorescence and hydrophobic ANS probe results. The recognition mechanism was found to be of static type, or rather the hemoglobin-malachite green complex formation occurred via noncovalent interactions such as π-π interactions, hydrogen bonds and hydrophobic interactions with an association constant of 10(4) M(-1). Moreover, the results also show that the spatial structure of the biopolymer was changed in the presence of malachite green with a decrease of the α-helix and increase of the β-sheet, turn and random coil suggesting protein damage, as derived from far-UV CD and three-dimensional fluorescence. Results of this work will help to further comprehend the molecular recognition of malachite green by the receptor protein and the possible toxicological profiles of other compounds, which are the metabolites and ramifications of malachite green.

  13. Intra-membrane molecular interactions of K+ channel proteins :

    SciTech Connect

    Moczydlowski, Edward G.

    2013-07-01

    Ion channel proteins regulate complex patterns of cellular electrical activity and ionic signaling. Certain K+ channels play an important role in immunological biodefense mechanisms of adaptive and innate immunity. Most ion channel proteins are oligomeric complexes with the conductive pore located at the central subunit interface. The long-term activity of many K+ channel proteins is dependent on the concentration of extracellular K+; however, the mechanism is unclear. Thus, this project focused on mechanisms underlying structural stability of tetrameric K+ channels. Using KcsA of Streptomyces lividans as a model K+ channel of known structure, the molecular basis of tetramer stability was investigated by: 1. Bioinformatic analysis of the tetramer interface. 2. Effect of two local anesthetics (lidocaine, tetracaine) on tetramer stability. 3. Molecular simulation of drug docking to the ion conduction pore. The results provide new insights regarding the structural stability of K+ channels and its possible role in cell physiology.

  14. Investigation of hydrogen bonded molecular solids by diffraction, spectroscopy, and computational chemistry

    NASA Astrophysics Data System (ADS)

    Hudson, Matthew R.

    The nature of hydrogen-bonding interactions in the solid state is examined through the investigation of molecular crystals by incoherent inelastic neutron scattering (INS) spectroscopy, Raman spectroscopy, X-ray and neutron diffraction, and computational chemistry. The molecular solids studied range from small organic molecules to larger inorganic acid salts. Hydrogen bonding is the primary mode of interaction in the solid state for each of the systems studied. INS spectra were collected at 25 K for each molecular solid and the motions of the hydrogen atoms assigned. Raman spectra were collected at 78 and 298 K to aid in the molecular mode assignments of the INS spectra and to examine possible phase changes as a function of temperature. Neutron diffraction was employed, when possible, to accurately locate the hydrogen atom positions, and X-ray diffraction was performed to obtain accurate unit cell dimensions and to obtain initial characterizations of the samples. The diffraction structures served as the basis for solid-state density functional theory (DFT) calculations. DFT simulations were used to aid in the vibrational normal mode assignments, to investigate possible solid-phase transitions, and as a test of the limits of basis sets and the available DFT theory. Of the six molecular solids studied, several important observations were made: (1) the determination of a structural phase transition in L-alanine alaninium nitrate by both spectroscopic and theoretical methods, (2) the structure of picolinic acid was elucidated at 25 K and room-temperature by the combination of INS and theory, (3) glycine lithium sulfate was found to be a useful test of DFT to accurately optimize the structure and calculate the normal modes of a complex 3D network of hydrogen-bonding interactions, (4) nicotinic acid was found to be a useful test of one dimensional hydrogen-bonding interactions with pi-stacking interactions dominating the orthogonal directions, and (5) parabanic acid

  15. Molecular self-assembly for biological investigations and nanoscale lithography

    NASA Astrophysics Data System (ADS)

    Cheunkar, Sarawut

    Small, diffusible molecules when recognized by their binding partners, such as proteins and antibodies, trigger enzymatic activity, cell communication, and immune response. Progress in analytical methods enabling detection, characterization, and visualization of biological dynamics at the molecular level will advance our exploration of complex biological systems. In this dissertation, analytical platforms were fabricated to capture membrane-associated receptors, which are essential proteins in cell signaling pathways. The neurotransmitter serotonin and its biological precursor were immobilized on gold substrates coated with self-assembled monolayers (SAMs) of oligo(ethylene glycol)alkanethiols and their reactive derivatives. The SAM-coated substrates present the biologically selective affinity of immobilized molecules to target native membrane-associated receptors. These substrates were also tested for biospecificity using antibodies. In addition, small-molecule-functionalized platforms, expressing neurotransmitter pharmacophores, were employed to examine kinetic interactions between G-protein-coupled receptors and their associated neurotransmitters. The binding interactions were monitored using a quartz crystal microbalance equipped with liquid-flow injection. The interaction kinetics of G-protein-coupled serotonin 1A receptor and 5-hydroxytyptophan-functionalized surfaces were studied in a real-time, label-free environment. Key binding parameters, such as equilibrium dissociation constants, binding rate constants, and dissociative half-life, were extracted. These parameters are critical for understanding and comparing biomolecular interactions in modern biomedical research. By integrating self-assembly, surface functionalization, and nanofabrication, small-molecule microarrays were created for high-throughput screening. A hybrid soft-lithography, called microcontact insertion printing, was used to pattern small molecules at the dilute scales necessary for highly

  16. Probing the interaction of troxerutin with transfer RNA by spectroscopic and molecular modeling.

    PubMed

    Subastri, A; Ramamurthy, C H; Suyavaran, A; Lokeswara Rao, P; Preedia Babu, E; Hari Krishna, K; Suresh Kumar, M; Thirunavukkarasu, C

    2015-12-01

    The studies on the interaction between tRNA (transfer RNA) and small molecules are an area of remarkable recent attention. For this notion a fundamental knowledge of the molecular features involving the interaction of small molecules with tRNA is crucial. Hence, in the present study we have investigated the interaction of TXER (troxerutin), natural bioflavonoid rutin derivative with yeast tRNA by using various spectroscopic techniques and molecular docking studies. The UV absorption and fluorescence emission studies demonstrated external binding of TXER on tRNA with low binding constant values as compared to strong binders. Circular dichroism (CD) spectroscopy study revealed that TXER did not show any significant modification on native conformation of tRNA. Furthermore in electrochemical study, the complex of TXER-tRNA did not expose any noticeable positive potential peak shift which indicated an interaction of TXER with tRNA by electrostatic or external binding mode. The docking study showed that the hydrogen and hydrophobic interactions were involved in binding of TXER-tRNA with docking score -7.0 kcal/mol. These findings led us to confirm the interaction of TXER on tRNA through external binding with low binding affinity, indicating its potential bioapplication in the future.

  17. Compatibility polymorphism in snail/schistosome interactions: From field to theory to molecular mechanisms

    PubMed Central

    Mitta, G.; Adema, C.M.; Gourbal, B.; Loker, E.S.; Theron, A.

    2013-01-01

    Coevolutionary dynamics in host–parasite interactions potentially lead to an arms race that results in compatibility polymorphism. The mechanisms underlying compatibility have remained largely unknown in the interactions between the snail Biomphalaria glabrata and Schistosoma mansoni, one of the agents of human schistosomiasis. This review presents a combination of data obtained from field and laboratory studies arguing in favor of a matching phenotype model to explain compatibility polymorphism. Investigations focused on the molecular determinants of compatibility have revealed two repertoires of polymorphic and/or diversified molecules that have been shown to interact: the parasite antigens S. mansoni polymorphic mucins and the B. glabrata fibrinogen-related proteins immune receptors. We hypothesize their interactions define the compatible/incompatible status of a specific snail/schistosome combination. This line of thought suggests concrete approaches amenable to testing in field-oriented studies attempting to control schistosomiasis by disrupting schistosome–snail compatibility. PMID:21945832

  18. Thermal and molecular investigation of laser tissue welding

    SciTech Connect

    Small, W., IV

    1998-06-01

    Despite the growing number of successful animal and human trials, the exact mechanisms of laser tissue welding remain unknown. Furthermore, the effects of laser heating on tissue on the molecular scale are not fully understood. To address these issues, a multi-front attack oil both extrinsic (solder/patch mediated) and intrinsic (laser only) tissue welding was launched using two-color infrared thermometry, computer modeling, weld strength assessment, biochemical assays, and vibrational spectroscopy. The coupling of experimentally measured surface temperatures with the predictive numerical simulations provided insight into the sub-surface dynamics of the laser tissue welding process. Quantification of the acute strength of the welds following the welding procedure enabled comparison among trials during an experiment, with previous experiments, and with other studies in the literature. The acute weld integrity also provided an indication of tile probability of long-term success. Molecular effects induced In the tissue by laser irradiation were investigated by measuring tile concentrations of specific collagen covalent crosslinks and characterizing the Fourier-Transform infrared (FTIR) spectra before and after the laser exposure.

  19. Interactive display of molecular models using a microcomputer system

    NASA Technical Reports Server (NTRS)

    Egan, J. T.; Macelroy, R. D.

    1980-01-01

    A simple, microcomputer-based, interactive graphics display system has been developed for the presentation of perspective views of wire frame molecular models. The display system is based on a TERAK 8510a graphics computer system with a display unit consisting of microprocessor, television display and keyboard subsystems. The operating system includes a screen editor, file manager, PASCAL and BASIC compilers and command options for linking and executing programs. The graphics program, written in USCD PASCAL, involves the centering of the coordinate system, the transformation of centered model coordinates into homogeneous coordinates, the construction of a viewing transformation matrix to operate on the coordinates, clipping invisible points, perspective transformation and scaling to screen coordinates; commands available include ZOOM, ROTATE, RESET, and CHANGEVIEW. Data file structure was chosen to minimize the amount of disk storage space. Despite the inherent slowness of the system, its low cost and flexibility suggests general applicability.

  20. Molecular and chemical dialogues in bacteria-protozoa interactions

    PubMed Central

    Song, Chunxu; Mazzola, Mark; Cheng, Xu; Oetjen, Janina; Alexandrov, Theodore; Dorrestein, Pieter; Watrous, Jeramie; van der Voort, Menno; Raaijmakers, Jos M.

    2015-01-01

    Protozoan predation of bacteria can significantly affect soil microbial community composition and ecosystem functioning. Bacteria possess diverse defense strategies to resist or evade protozoan predation. For soil-dwelling Pseudomonas species, several secondary metabolites were proposed to provide protection against different protozoan genera. By combining whole-genome transcriptome analyses with (live) imaging mass spectrometry (IMS), we observed multiple changes in the molecular and chemical dialogues between Pseudomonas fluorescens and the protist Naegleria americana. Lipopeptide (LP) biosynthesis was induced in Pseudomonas upon protozoan grazing and LP accumulation transitioned from homogeneous distributions across bacterial colonies to site-specific accumulation at the bacteria-protist interface. Also putrescine biosynthesis was upregulated in P. fluorescens upon predation. We demonstrated that putrescine induces protozoan trophozoite encystment and adversely affects cyst viability. This multifaceted study provides new insights in common and strain-specific responses in bacteria-protozoa interactions, including responses that contribute to bacterial survival in highly competitive soil and rhizosphere environments. PMID:26246193

  1. Integrating pathways of Parkinson's disease in a molecular interaction map.

    PubMed

    Fujita, Kazuhiro A; Ostaszewski, Marek; Matsuoka, Yukiko; Ghosh, Samik; Glaab, Enrico; Trefois, Christophe; Crespo, Isaac; Perumal, Thanneer M; Jurkowski, Wiktor; Antony, Paul M A; Diederich, Nico; Buttini, Manuel; Kodama, Akihiko; Satagopam, Venkata P; Eifes, Serge; Del Sol, Antonio; Schneider, Reinhard; Kitano, Hiroaki; Balling, Rudi

    2014-02-01

    Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a complex interplay of genetic and environmental factors. Information on various aspects of PD pathogenesis is rapidly increasing and needs to be efficiently organized, so that the resulting data is available for exploration and analysis. Here we introduce a computationally tractable, comprehensive molecular interaction map of PD. This map integrates pathways implicated in PD pathogenesis such as synaptic and mitochondrial dysfunction, impaired protein degradation, alpha-synuclein pathobiology and neuroinflammation. We also present bioinformatics tools for the analysis, enrichment and annotation of the map, allowing the research community to open new avenues in PD research. The PD map is accessible at http://minerva.uni.lu/pd_map .

  2. Collapse and coexistence for a molecular braid with an attractive interaction component subject to mechanical forces

    NASA Astrophysics Data System (ADS)

    (O' Lee, Dominic J.

    2015-04-01

    Dual mechanical braiding experiments provide a useful tool with which to investigate the nature of interactions between rod-like molecules, for instance actin and DNA. In conditions close to molecular condensation, one would expect an appearance of a local minimum in the interaction potential between the two molecules. We investigate this situation, introducing an attractive component into the interaction potential, using a model developed for describing such experiments. We consider both attractive interactions that do not depend on molecular structure and those which depend on a DNA-like helix structure. In braiding experiments, an attractive term may lead to certain effects. A local minimum may cause molecules to collapse from a loosely braided configuration into a tight one, occurring at a critical value of the moment applied about the axis of the braid. For a fixed number of braid pitches, this may lead to coexistence between the two braiding states, tight and loose. Coexistence implies certain proportions of the braid are in each state, their relative size depending on the number of braid pitches. This manifests itself as a linear dependence in numerically calculated quantities as functions of the number of braid pitches. Also, in the collapsed state, the braid radius stays roughly constant. Furthermore, if the attractive interaction is helix dependent, the left-right handed braid symmetry is broken. For a DNA like charge distribution, using the Kornyshev-Leikin interaction model, our results suggest that significant braid collapse and coexistence only occurs for left handed braids. Regardless of the interaction model, the study highlights the possible qualitative physics of braid collapse and coexistence; and the role helix specific forces might play, if important. The model could be used to connect other microscopic theories of interaction with braiding experiments.

  3. Ligand binding to anti-cancer target CD44 investigated by molecular simulations.

    PubMed

    Nguyen, Tin Trung; Tran, Duy Phuoc; Pham Dinh Quoc Huy; Hoang, Zung; Carloni, Paolo; Van Pham, Phuc; Nguyen, Chuong; Li, Mai Suan

    2016-07-01

    CD44 is a cell-surface glycoprotein and receptor for hyaluronan, one of the major components of the tumor extracellular matrix. There is evidence that the interaction between CD44 and hyaluronan promotes breast cancer metastasis. Recently, the molecule F-19848A was shown to inhibit hyaluronan binding to receptor CD44 in a cell-based assay. In this study, we investigated the mechanism and energetics of F-19848A binding to CD44 using molecular simulation. Using the molecular mechanics/Poisson Boltzmann surface area (MM-PBSA) method, we obtained the binding free energy and inhibition constant of the complex. The van der Waals (vdW) interaction and the extended portion of F-19848A play key roles in the binding affinity. We screened natural products from a traditional Chinese medicine database to search for CD44 inhibitors. From combining pharmaceutical requirements with docking and molecular dynamics simulations, we found ten compounds that are potentially better or equal to the F-19848A ligand at binding to CD44 receptor. Therefore, we have identified new candidates of CD44 inhibitors, based on molecular simulation, which may be effective small molecules for the therapy of breast cancer. PMID:27342250

  4. Theoretical investigation of the molecular structure of the isoquercitrin molecule

    NASA Astrophysics Data System (ADS)

    Cornard, J. P.; Boudet, A. C.; Merlin, J. C.

    1999-09-01

    Isoquercitrin is a glycosilated flavonoid that has received a great deal of attention because of its numerous biological effects. We present a theoretical study on isoquercitrin using both empirical (Molecular Mechanics (MM), with MMX force field) and quantum chemical (AM1 semiempirical method) techniques. The most stable structures of the molecule obtained by MM calculations have been used as input data for the semiempirical treatment. The position and orientation of the glucose moiety with regard to the remainder of the molecule have been investigated. The flexibility of isoquercitrin principally lies in rotations around the inter-ring bond and the sugar link. In order to know the structural modifications generated by the substitution by a sugar, geometrical parameters of quercetin (aglycon) and isoquercitrin have been compared. The good accordance between theoretical and experimental electronic spectra permits to confirm the reliability of the structural model.

  5. Molecular-dynamics investigation of the desensitization of detonable material

    NASA Astrophysics Data System (ADS)

    Rice, Betsy M.; Mattson, William; Trevino, Samuel F.

    1998-05-01

    A molecular-dynamics investigation of the effects of a diluent on the detonation of a model crystalline explosive is presented. The diluent, a heavy material that cannot exothermally react with any species of the system, is inserted into the crystalline explosive in two ways. The first series of simulations investigates the attenuation of the energy of a detonation wave in a pure explosive after it encounters a small layer of crystalline diluent that has been inserted into the lattice of the pure explosive. After the shock wave has traversed the diluent layer, it reenters the pure explosive. Unsupported detonation is not reestablished unless the energy of the detonation wave exceeds a threshold value. The second series of simulations investigates detonation of solid solutions of different concentrations of the explosive and diluent. For both types of simulations, the key to reestablishing or reaching unsupported detonation is the attainment of a critical number density behind the shock front. Once this critical density is reached, the explosive molecules make a transition to an atomic phase. This is the first step in the reaction mechanism that leads to the heat release that sustains the detonation. The reactive fragments formed from the atomization of the heteronuclear reactants subsequently combine with new partners, with homonuclear product formation exothermally favored. The results of detonation of the explosive-diluent crystals are consistent with those presented in an earlier study on detonation of pure explosive [B. M. Rice, W. Mattson, J. Grosh, and S. F. Trevino, Phys. Rev. E 53, 611 (1996)].

  6. Creep rupture of fiber bundles: A molecular dynamics investigation

    NASA Astrophysics Data System (ADS)

    Linga, G.; Ballone, P.; Hansen, Alex

    2015-08-01

    The creep deformation and eventual breaking of polymeric samples under a constant tensile load F is investigated by molecular dynamics based on a particle representation of the fiber bundle model. The results of the virtual testing of fibrous samples consisting of 40 000 particles arranged on Nc=400 chains reproduce characteristic stages seen in the experimental investigations of creep in polymeric materials. A logarithmic plot of the bundle lifetime τ versus load F displays a marked curvature, ruling out a simple power-law dependence of τ on F . A power law τ ˜F-4 , however, is recovered at high load. We discuss the role of reversible bond breaking and formation on the eventual fate of the sample and simulate a different type of creep testing, imposing a constant stress rate on the sample up to its breaking point. Our simulations, relying on a coarse-grained representation of the polymer structure, introduce new features into the standard fiber bundle model, such as real-time dynamics, inertia, and entropy, and open the way to more detailed models, aiming at material science aspects of polymeric fibers, investigated within a sound statistical mechanics framework.

  7. Spectroscopy and molecular docking study on the interaction behavior between nobiletin and pepsin.

    PubMed

    Zeng, Hua-jin; Qi, Tingting; Yang, Ran; You, Jing; Qu, Ling-bo

    2014-07-01

    In this study, the binding mode of nobiletin (NOB) with pepsin was investigated by spectroscopic and molecular docking methods. NOB can interact with pepsin to form a NOB-pepsin complex. The binding constant, number of binding sites and thermodynamic parameters were measured, which indicated that NOB could spontaneously bind with pepsin through hydrophobic and electrostatic forces with one binding site. Molecular docking results revealed that NOB bound into the pepsin cavity. Synchronous and three-dimensional fluorescence spectra results provide data concerning conformational and some micro-environmental changes of pepsin. Furthermore, the binding of NOB can inhibit pepsin activity in vitro. The present study provides direct evidence at a molecular level to show that NOB could induce changes in the enzyme pepsin structure and function.

  8. Cryo-bioorganic chemistry: molecular interactions at low temperature.

    PubMed

    Vajda, T

    1999-10-30

    Freezing of aqueous or organic solutions plays a pivotal role in enhancement of rate and/or yield of biomolecular reactions. The smooth conditions of the frozen state at low temperature can also suppress racemization and side-product formation of the reactions. Molecular interactions in liquid undercooled solutions, on the other hand, offer the possibility to study enzyme activity mechanisms in vitro and a chance for survival of organisms in vivo. This review illustrates the differences between frozen and liquid conditions on several small and large biomolecules, together with the synthetic use of freezing. In relation to the freezing effect on enzyme activity, a peculiar phenomenon is discussed: 'cryo-oscillations' are temporal motions of trypsin activity in frozen solution in the presence of Mn2+ ion. The molecular basis of cold adaptation is also discussed, which points to mechanisms evolved by organisms living at subzero temperatures. The factors involved in the freezing effect are shown; i.e. the role of freeze-concentration and frozen solvent surface is demonstrated and elucidated using several examples. PMID:11212294

  9. Investigation of high voltage spacecraft system interactions with plasma environments

    NASA Technical Reports Server (NTRS)

    Stevens, N. J.; Berkopec, F. D.; Purvis, C. K.; Grier, N.; Staskus, J.

    1978-01-01

    The exposure of high voltage spacecraft systems to the charged particle environment of space can produce interactions that will influence system operation. An experimental investigation of these interactions has been undertaken for insulator and conductor test surfaces biased up to plus or minus 1 kV in a simulated low earth orbit charged particle environment. It has been found that these interactions are controlled by the insulator surfaces surrounding the biased conductors. For positive applied voltages the electron current collection can be enhanced by the insulators. For negative applied voltages the insulator surface confines the voltage to the conductor region; this can cause arcing. Understanding these interactions and the technology to control their impact on system operation is essential to the design of solar cell arrays for ion drive propulsion applications that use direct drive power processing.

  10. The DigitalSeed: An Interactive Toy for Investigating Plants

    ERIC Educational Resources Information Center

    Cherubini, Mauro; Gash, Hugh; McCloughlin, Thomas

    2008-01-01

    Plant growth, development and reproduction are fundamental concepts in biology; yet there is a recorded lack of motivation for young people to grapple with these concepts. Here we present the "DigitalSeed" toy for making investigations around these concepts more accessible to children through hands-on digital interaction. This is part of an…

  11. Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments

    PubMed Central

    Shen, Rong; Han, Wei; Fiorin, Giacomo; Islam, Shahidul M.; Schulten, Klaus; Roux, Benoît

    2015-01-01

    The knowledge of multiple conformational states is a prerequisite to understand the function of membrane transport proteins. Unfortunately, the determination of detailed atomic structures for all these functionally important conformational states with conventional high-resolution approaches is often difficult and unsuccessful. In some cases, biophysical and biochemical approaches can provide important complementary structural information that can be exploited with the help of advanced computational methods to derive structural models of specific conformational states. In particular, functional and spectroscopic measurements in combination with site-directed mutations constitute one important source of information to obtain these mixed-resolution structural models. A very common problem with this strategy, however, is the difficulty to simultaneously integrate all the information from multiple independent experiments involving different mutations or chemical labels to derive a unique structural model consistent with the data. To resolve this issue, a novel restrained molecular dynamics structural refinement method is developed to simultaneously incorporate multiple experimentally determined constraints (e.g., engineered metal bridges or spin-labels), each treated as an individual molecular fragment with all atomic details. The internal structure of each of the molecular fragments is treated realistically, while there is no interaction between different molecular fragments to avoid unphysical steric clashes. The information from all the molecular fragments is exploited simultaneously to constrain the backbone to refine a three-dimensional model of the conformational state of the protein. The method is illustrated by refining the structure of the voltage-sensing domain (VSD) of the Kv1.2 potassium channel in the resting state and by exploring the distance histograms between spin-labels attached to T4 lysozyme. The resulting VSD structures are in good agreement with

  12. Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments.

    PubMed

    Shen, Rong; Han, Wei; Fiorin, Giacomo; Islam, Shahidul M; Schulten, Klaus; Roux, Benoît

    2015-10-01

    The knowledge of multiple conformational states is a prerequisite to understand the function of membrane transport proteins. Unfortunately, the determination of detailed atomic structures for all these functionally important conformational states with conventional high-resolution approaches is often difficult and unsuccessful. In some cases, biophysical and biochemical approaches can provide important complementary structural information that can be exploited with the help of advanced computational methods to derive structural models of specific conformational states. In particular, functional and spectroscopic measurements in combination with site-directed mutations constitute one important source of information to obtain these mixed-resolution structural models. A very common problem with this strategy, however, is the difficulty to simultaneously integrate all the information from multiple independent experiments involving different mutations or chemical labels to derive a unique structural model consistent with the data. To resolve this issue, a novel restrained molecular dynamics structural refinement method is developed to simultaneously incorporate multiple experimentally determined constraints (e.g., engineered metal bridges or spin-labels), each treated as an individual molecular fragment with all atomic details. The internal structure of each of the molecular fragments is treated realistically, while there is no interaction between different molecular fragments to avoid unphysical steric clashes. The information from all the molecular fragments is exploited simultaneously to constrain the backbone to refine a three-dimensional model of the conformational state of the protein. The method is illustrated by refining the structure of the voltage-sensing domain (VSD) of the Kv1.2 potassium channel in the resting state and by exploring the distance histograms between spin-labels attached to T4 lysozyme. The resulting VSD structures are in good agreement with

  13. Molecular interactions in the priming complex of bacteriophage T7

    PubMed Central

    Kulczyk, Arkadiusz W.; Richardson, Charles C.

    2012-01-01

    The lagging-strand DNA polymerase requires an oligoribonucleotide, synthesized by DNA primase, to initiate the synthesis of an Okazaki fragment. In the replication system of bacteriophage T7 both DNA primase and DNA helicase activities are contained within a single protein, the bifunctional gene 4 protein (gp4). Intermolecular interactions between gp4 and T7 DNA polymerase are crucial for the stabilization of the oligoribonucleotide, its transfer to the polymerase, and its extension by DNA polymerase. We have identified conditions necessary to assemble the T7 priming complex and characterized its biophysical properties using fluorescence anisotropy. In order to reveal molecular interactions that occur during delivery of the oligoribonucleotide to DNA polymerase, we have used four genetically altered gp4 to demonstrate that both the RNA polymerase and the zinc-finger domains of DNA primase are involved in the stabilization of the priming complex and in sequence recognition in the DNA template. We find that the helicase domain of gp4 contributes to the stability of the complex by binding to the ssDNA template. The C-terminal tail of gp4 is not required for complex formation. PMID:22645372

  14. Molecular Dynamics of "Fuzzy" Transcriptional Activator-Coactivator Interactions

    PubMed Central

    Scholes, Natalie S.; Weinzierl, Robert O. J.

    2016-01-01

    Transcriptional activation domains (ADs) are generally thought to be intrinsically unstructured, but capable of adopting limited secondary structure upon interaction with a coactivator surface. The indeterminate nature of this interface made it hitherto difficult to study structure/function relationships of such contacts. Here we used atomistic accelerated molecular dynamics (aMD) simulations to study the conformational changes of the GCN4 AD and variants thereof, either free in solution, or bound to the GAL11 coactivator surface. We show that the AD-coactivator interactions are highly dynamic while obeying distinct rules. The data provide insights into the constant and variable aspects of orientation of ADs relative to the coactivator, changes in secondary structure and energetic contributions stabilizing the various conformers at different time points. We also demonstrate that a prediction of α-helical propensity correlates directly with the experimentally measured transactivation potential of a large set of mutagenized ADs. The link between α-helical propensity and the stimulatory activity of ADs has fundamental practical and theoretical implications concerning the recruitment of ADs to coactivators. PMID:27175900

  15. Molecular interactions between (-)-epigallocatechin gallate analogs and pancreatic lipase.

    PubMed

    Wang, Shihui; Sun, Zeya; Dong, Shengzhao; Liu, Yang; Liu, Yun

    2014-01-01

    The molecular interactions between pancreatic lipase (PL) and four tea polyphenols (EGCG analogs), like (-)-epigallocatechin gallate (EGCG), (-)-gallocatechin gallate (GCG), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin (EC), were studied from PL activity, conformation, kinetics and thermodynamics. It was observed that EGCG analogs inhibited PL activity, and their inhibitory rates decreased by the order of EGCG>GCG>ECG>EC. PL activity at first decreased rapidly and then slowly with the increase of EGCG analogs concentrations. α-Helix content of PL secondary structure decreased dependent on EGCG analogs concentration by the order of EGCG>GCG>ECG>EC. EGCG, ECG, and EC could quench PL fluorescence both dynamically and statically, while GCG only quenched statically. EGCG analogs would induce PL self-assembly into complexes and the hydrodynamic radii of the complexes possessed a close relationship with the inhibitory rates. Kinetics analysis showed that EGCG analogs non-competitively inhibited PL activity and did not bind to PL catalytic site. DSC measurement revealed that EGCG analogs decreased the transition midpoint temperature of PL enzyme, suggesting that these compounds reduced PL enzyme thermostability. In vitro renaturation through urea solution indicated that interactions between PL and EGCG analogs were weak and non-covalent. PMID:25365042

  16. Multitargeting by curcumin as revealed by molecular interaction studies

    PubMed Central

    Gupta, Subash C.; Prasad, Sahdeo; Kim, Ji Hye; Patchva, Sridevi; Webb, Lauren J.; Priyadarsini, Indira K.

    2012-01-01

    Curcumin (diferuloylmethane), the active ingredient in turmeric (Curcuma longa), is a highly pleiotropic molecule with anti-inflammatory, anti-oxidant, chemopreventive, chemosensitization, and radiosensitization activities. The pleiotropic activities attributed to curcumin come from its complex molecular structure and chemistry, as well as its ability to influence multiple signaling molecules. Curcumin has been shown to bind by multiple forces directly to numerous signaling molecules, such as inflammatory molecules, cell survival proteins, protein kinases, protein reductases, histone acetyltransferase, histone deacetylase, glyoxalase I, xanthine oxidase, proteasome, HIV1 integrase, HIV1 protease, sarco (endo) plasmic reticulum Ca2+ ATPase, DNA methyltransferases 1, FtsZ protofilaments, carrier proteins, and metal ions. Curcumin can also bind directly to DNA and RNA. Owing to its β-diketone moiety, curcumin undergoes keto–enol tautomerism that has been reported as a favorable state for direct binding. The functional groups on curcumin found suitable for interaction with other macromolecules include the α, β-unsaturated β-diketone moiety, carbonyl and enolic groups of the β-diketone moiety, methoxy and phenolic hydroxyl groups, and the phenyl rings. Various biophysical tools have been used to monitor direct interaction of curcumin with other proteins, including absorption, fluorescence, Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopy, surface plasmon resonance, competitive ligand binding, Forster type fluorescence resonance energy transfer (FRET), radiolabeling, site-directed mutagenesis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), immunoprecipitation, phage display biopanning, electron microscopy, 1-anilino-8-naphthalene-sulfonate (ANS) displacement, and co-localization. Molecular docking, the most commonly employed computational tool for calculating binding affinities and predicting

  17. Family interaction and adolescent suicidal behaviour: a preliminary investigation.

    PubMed

    Williams, C; Lyons, C M

    1976-09-01

    While investigators have emphasized the importance of familial relations in the production of suicidal behaviour in adolescence, experimental evaluation of specific family interaction processes has, thus far, been neglected. The aim of the present study was to investigate possible relationships between adolescent suicidal behaviour and total on-going family functioning. Hypotheses were advanced to evaluate the communication, interaction and reinforcement patterns in families. A modified revealed differences technique was employed to elicit standardized segments of interaction which were video-taped and later studied by two independent raters. The sample consisted of twelve individually matched, intact family tetrads, six normal (N) and six containing an adolescent female who had exhibited suicidal behaviour (SM). Results suggest that SM families constitute a malfunctioning system which can be differentiated from that of normal samples. As compared with the N group, SM family interaction evidenced less effective productivity, specificity, and adaptive interaction, and higher rates of conflict and negative reinforcement. Overall findings were discussed in terms of current family theory and their possible relationship to the genesis, maintenance and management of some classes of suicidal behaviour.

  18. Insights into the molecular interactions between aminopeptidase and amyloid beta peptide using molecular modeling techniques.

    PubMed

    Dhanavade, Maruti J; Sonawane, Kailas D

    2014-08-01

    Amyloid beta (Aβ) peptides play a central role in the pathogenesis of Alzheimer's disease. The accumulation of Aβ peptides in AD brain was caused due to overproduction or insufficient clearance and defects in the proteolytic degradation of Aβ peptides. Hence, Aβ peptide degradation could be a promising therapeutic approach in AD treatment. Recent experimental report suggests that aminopeptidase from Streptomyces griseus KK565 (SGAK) can degrade Aβ peptides but the interactive residues are yet to be known in detail at the atomic level. Hence, we developed the three-dimensional model of aminopeptidase (SGAK) using SWISS-MODEL, Geno3D and MODELLER. Model built by MODELLER was used for further studies. Molecular docking was performed between aminopeptidase (SGAK) with wild-type and mutated Aβ peptides. The docked complex of aminopeptidase (SGAK) and wild-type Aβ peptide (1IYT.pdb) shows more stability than the other complexes. Molecular docking and MD simulation results revealed that the residues His93, Asp105, Glu139, Glu140, Asp168 and His255 are involved in the hydrogen bonding with Aβ peptide and zinc ions. The interactions between carboxyl oxygen atoms of Glu139 of aminopeptidase (SGAK) with water molecule suggest that the Glu139 may be involved in the nucleophilic attack on Ala2-Glu3 peptide bond of Aβ peptide. Hence, amino acid Glu139 of aminopeptidase (SGAK) might play an important role to degrade Aβ peptides, a causative agent of Alzheimer's disease.

  19. Investigation of high voltage spacecraft system interactions with plasma environments

    NASA Technical Reports Server (NTRS)

    Stevens, N. J.; Berkopec, F. D.; Purvis, C. K.; Grier, N.; Staskus, J. V.

    1978-01-01

    An experimental investigation was undertaken for insulator and conductor test surfaces biased up to + or - 1kV in a simulated low earth orbit charged particle environment. It was found that these interactions are controlled by the insulator surfaces surrounding the biased conductors. For positive applied voltages the electron current collection can be enhanced by the insulators. For negative applied voltages the insulator surface confines the voltage to the conductor region. Understanding these interactions and the technology to control their impact on system operation is essential to the design of solar cell arrays for ion drive propulsion applications that use direct drive power processing.

  20. Enhancing Metagenomics Investigations of Microbial Interactions with Biofilm Technology

    PubMed Central

    McLean, Robert J. C.; Kakirde, Kavita S.

    2013-01-01

    Investigations of microbial ecology and diversity have been greatly enhanced by the application of culture-independent techniques. One such approach, metagenomics, involves sample collections from soil, water, and other environments. Extracted nucleic acids from bulk environmental samples are sequenced and analyzed, which allows microbial interactions to be inferred on the basis of bioinformatics calculations. In most environments, microbial interactions occur predominately in surface-adherent, biofilm communities. In this review, we address metagenomics sampling and biofilm biology, and propose an experimental strategy whereby the resolving power of metagenomics can be enhanced by incorporating a biofilm-enrichment step during sample acquisition. PMID:24284397

  1. Enhancing metagenomics investigations of microbial interactions with biofilm technology.

    PubMed

    McLean, Robert J C; Kakirde, Kavita S

    2013-11-11

    Investigations of microbial ecology and diversity have been greatly enhanced by the application of culture-independent techniques. One such approach, metagenomics, involves sample collections from soil, water, and other environments. Extracted nucleic acids from bulk environmental samples are sequenced and analyzed, which allows microbial interactions to be inferred on the basis of bioinformatics calculations. In most environments, microbial interactions occur predominately in surface-adherent, biofilm communities. In this review, we address metagenomics sampling and biofilm biology, and propose an experimental strategy whereby the resolving power of metagenomics can be enhanced by incorporating a biofilm-enrichment step during sample acquisition.

  2. Molecular Dynamics Investigation of the Substrate Binding Mechanism in Carboxylesterase

    DOE PAGESBeta

    Chen, Qi; Luan, Zheng-Jiao; Cheng, Xiaolin; Xu, Jian-He

    2015-02-25

    A recombinant carboxylesterase, cloned from Pseudomonas putida and designated as rPPE, is capable of catalyzing the bioresolution of racemic 2-acetoxy-2-(2 -chlorophenyl)acetate (rac-AcO-CPA) with excellent (S)-enantioselectivity. Semi-rational design of the enzyme showed that the W187H variant could increase the activity by ~100-fold compared to the wild type (WT) enzyme. In this study, we performed all-atom molecular dynamics (MD) simulations of both apo-rPPE and rPPE in complex with (S)-AcO-CPA to gain insights into the origin of the increased catalysis in the W187H mutant. Moreover, our results show differential binding of (S)-AcO-CPA in the WT and W187H enzymes, especially the interactions of themore » substrate with the two active site residues Ser159 and His286. The replacement of Trp187 by His leads to considerable structural rearrangement in the active site of W187H. Unlike in the WT rPPE, the cap domain in the W187 mutant shows an open conformation in the simulations of both apo and substrate-bound enzymes. This open conformation exposes the catalytic triad to the solvent through a water accessible channel, which may facilitate the entry of the substrate and/or the exit of the product. Binding free energy calculations confirmed that the substrate binds more strongly in W187H than in WT. Based on these computational results, furthermore, we predicted that the mutations W187Y and D287G might also be able to increase the substrate binding, thus improve the enzyme s catalytic efficiency. Experimental binding and kinetic assays on W187Y and D287G show improved catalytic efficiency over WT, but not W187H. Contrary to our prediction, W187Y shows slightly decreased substrate binding coupled with a 100 fold increase in turn-over rate, while in D287G the substrate binding is 8 times stronger but with a slightly reduced turn-over rate. Finally, our work provides important molecular-level insights into the binding of the (S)-AcO-CPA substrate to carboxylesterase r

  3. Molecular Dynamics Investigation of the Substrate Binding Mechanism in Carboxylesterase

    SciTech Connect

    Chen, Qi; Luan, Zheng-Jiao; Cheng, Xiaolin; Xu, Jian-He

    2015-02-25

    A recombinant carboxylesterase, cloned from Pseudomonas putida and designated as rPPE, is capable of catalyzing the bioresolution of racemic 2-acetoxy-2-(2 -chlorophenyl)acetate (rac-AcO-CPA) with excellent (S)-enantioselectivity. Semi-rational design of the enzyme showed that the W187H variant could increase the activity by ~100-fold compared to the wild type (WT) enzyme. In this study, we performed all-atom molecular dynamics (MD) simulations of both apo-rPPE and rPPE in complex with (S)-AcO-CPA to gain insights into the origin of the increased catalysis in the W187H mutant. Moreover, our results show differential binding of (S)-AcO-CPA in the WT and W187H enzymes, especially the interactions of the substrate with the two active site residues Ser159 and His286. The replacement of Trp187 by His leads to considerable structural rearrangement in the active site of W187H. Unlike in the WT rPPE, the cap domain in the W187 mutant shows an open conformation in the simulations of both apo and substrate-bound enzymes. This open conformation exposes the catalytic triad to the solvent through a water accessible channel, which may facilitate the entry of the substrate and/or the exit of the product. Binding free energy calculations confirmed that the substrate binds more strongly in W187H than in WT. Based on these computational results, furthermore, we predicted that the mutations W187Y and D287G might also be able to increase the substrate binding, thus improve the enzyme s catalytic efficiency. Experimental binding and kinetic assays on W187Y and D287G show improved catalytic efficiency over WT, but not W187H. Contrary to our prediction, W187Y shows slightly decreased substrate binding coupled with a 100 fold increase in turn-over rate, while in D287G the substrate binding is 8 times stronger but with a slightly reduced turn-over rate. Finally, our work provides important molecular-level insights into the binding of the (S)-AcO-CPA substrate to carboxylesterase r

  4. A probe to study the toxic interaction of tartrazine with bovine hemoglobin at the molecular level.

    PubMed

    Li, Yating; Wei, Haoran; Liu, Rutao

    2014-03-01

    Tartrazine is an artificial azo dye commonly used in food products, but tartrazine in the environment is potentially harmful. The toxic interaction between tartrazine and bovine hemoglobin (BHb) was investigated using fluorescence, synchronous fluorescence, UV-vis absorption, circular dichroism (CD) and molecular modeling techniques under simulated physiological conditions. The fluorescence data showed that tartrazine can bind with BHb to form a complex. The binding process was a spontaneous molecular interaction, in which van der Waals' forces and hydrogen bonds played major roles. Molecular docking results showed that the hydrogen bonds exist between the oxygen atoms at position 31 of tartrazine and the nitrogen atom NZ7 on Lys99, and also between the oxygen atoms at position 15 of tartrazine and the nitrogen atom NZ7 on Lys104, Lys105. The results of UV-vis and CD spectra revealed that tartrazine led to conformational changes in BHb, including loosening of the skeleton structure and decreasing α helix in the secondary structure. The synchronous fluorescence experiment revealed that tartrazine binds into the hemoglobin central cavity, and this was verified using a molecular modeling study. PMID:23653408

  5. Spectroscopic investigation of interaction between mangiferin and bovine serum albumin

    NASA Astrophysics Data System (ADS)

    Lin, Hui; Lan, Jingfeng; Guan, Min; Sheng, Fenling; Zhang, Haixia

    2009-09-01

    The mechanism of interaction between mangiferin (MA) and bovine serum albumin (BSA) in aqueous solution was investigated by fluorescence spectra, synchronous fluorescence spectra, absorbance spectra and Fourier transform infrared (FT-IR) spectroscopy. The binding constants and binding sites of MA to BSA at different reaction times were calculated. And the distance between MA and BSA was estimated to be 5.20 nm based on Föster's theory. In addition, synchronous fluorescence and FT-IR measurements revealed that the secondary structures of the protein changed after the interaction of MA with BSA. As a conclusion, the interaction between the anti-diabetes Chinese medicine MA and BSA may provide some significant information for the mechanism of the traditional chinese medicine MA on the protein level to cure diabetes or other diseases.

  6. Molecular Interaction Mechanism between 2-Mercaptobenzimidazole and Copper-Zinc Superoxide Dismutase

    PubMed Central

    Teng, Yue; Zou, Luyi; Huang, Ming; Chen, Yadong

    2014-01-01

    2-Mercaptobenzimidazole (MBI) is widely utilized as a corrosion inhibitor, copper-plating brightener and rubber accelerator. The residue of MBI in the environment is potentially harmful. In the present work, the toxic interaction of MBI with the important antioxidant enzyme copper-zinc superoxide dismutase (Cu/ZnSOD) was investigated using spectroscopic and molecular docking methods. MBI can interact with Cu/ZnSOD to form an MBI-Cu/ZnSOD complex. The binding constant, number of binding sites and thermodynamic parameters were measured, which indicated that MBI could spontaneously bind with Cu/ZnSOD with one binding site through hydrogen bonds and van der Waals forces. MBI bound into the Cu/ZnSOD interface of two subdomains, which caused some microenvironmental and secondary structure changes of Cu/ZnSOD and further resulted in the inhibition of Cu/ZnSOD activity. This work provides direct evidence at a molecular level to show that exposure to MBI could induce changes in the structure and function of the enzyme Cu/ZnSOD. The estimated methods in this work may be applied to probe molecular interactions of biomacromolecules and other pollutants and drugs. PMID:25157630

  7. Investigation of High-Temperature Slag/Copper/Spinel Interactions

    NASA Astrophysics Data System (ADS)

    De Wilde, Evelien; Bellemans, Inge; Campforts, Mieke; Guo, Muxing; Blanpain, Bart; Moelans, Nele; Verbeken, Kim

    2016-09-01

    An important cause for the mechanical entrainment of copper droplets in slags during primary and secondary copper production is their interaction with solid spinel particles, hindering the sedimentation of the copper droplets. In the present study, the interactions between the three phases involved (slag-Cu droplets-spinel solids) were investigated using an adapted sessile drop experiment, combined with detailed microstructural investigation of the interaction zone. An industrially relevant synthetic PbO-CaO-SiO2-Cu2O-Al2O3-FeO-ZnO slag system, a MgAl2O4 spinel particle, and pure copper were examined with electron microscopy after their brief interaction at 1523 K (1250 °C). Based on the experimental results, a mechanism depending on the interlinked dissolved Cu and oxygen contents within the slag is proposed to describe the origin of the phenomenon of sticking Cu alloy droplets. In addition, the oxygen potential gradient across the phases (i.e., liquid Cu, slag, and spinel) appears to affect the Cu entrainment, as deduced from a microstructural analysis.

  8. Ranking of Molecular Biomarker Interaction with Targeted DNA Nucleobases via Full Atomistic Molecular Dynamics

    PubMed Central

    Zhang, Wenjun; Wang, Ming L.; Cranford, Steven W.

    2016-01-01

    DNA-based sensors can detect disease biomarkers, including acetone and ethanol for diabetes and H2S for cardiovascular diseases. Before experimenting on thousands of potential DNA segments, we conduct full atomistic steered molecular dynamics (SMD) simulations to screen the interactions between different DNA sequences with targeted molecules to rank the nucleobase sensing performance. We study and rank the strength of interaction between four single DNA nucleotides (Adenine (A), Guanine (G), Cytosine (C), and Thymine (T)) on single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with acetone, ethanol, H2S and HCl. By sampling forward and reverse interaction paths, we compute the free-energy profiles of eight systems for the four targeted molecules. We find that dsDNA react differently than ssDNA to the targeted molecules, requiring more energy to move the molecule close to DNA as indicated by the potential of mean force (PMF). Comparing the PMF values of different systems, we obtain a relative ranking of DNA base for the detection of each molecule. Via the same procedure, we could generate a library of DNA sequences for the detection of a wide range of chemicals. A DNA sensor array built with selected sequences differentiating many disease biomarkers can be used in disease diagnosis and monitoring. PMID:26750747

  9. Interpretation of Association Behavior and Molecular Interactions in Binary Mixtures from Thermoacoustics and Molecular Compression Data

    NASA Astrophysics Data System (ADS)

    Shukla, Rajeev K.; Kumar, Atul; Srivastava, Urvashi; Srivastava, Kirti; Pandey, Vivek K.

    2016-09-01

    Density and acoustic velocity were measured for binary liquid mixtures of formamide, N-methylacetamide (NMA), dimethylformamide (DMF), and dimethylacetamide (DMA) with acetonitrile at atmospheric pressure and 293.15 K, 298.15 K, 303.15 K, 308.15 K, or 313.15 K over the concentration range 0.12 to 0.97. Models assuming association and nonassociation of the components of the mixtures were used to predict the behavior of the studied liquids, which would typically show weak interactions. The measured properties were fitted to the Redlich-Kister polynomial to estimate the binary coefficients and standard errors. The data were used to study the molecular interactions in the binary mixtures. Furthermore, the McAllister multibody interaction model was used to correlate the properties of the binary liquid mixtures. Testing of the nonassociation and association models for the different systems showed that, compared with the nonassociation model theoretical results, the association model theoretical results were more consistent with the experimental results.

  10. Ranking of Molecular Biomarker Interaction with Targeted DNA Nucleobases via Full Atomistic Molecular Dynamics

    NASA Astrophysics Data System (ADS)

    Zhang, Wenjun; Wang, Ming L.; Cranford, Steven W.

    2016-01-01

    DNA-based sensors can detect disease biomarkers, including acetone and ethanol for diabetes and H2S for cardiovascular diseases. Before experimenting on thousands of potential DNA segments, we conduct full atomistic steered molecular dynamics (SMD) simulations to screen the interactions between different DNA sequences with targeted molecules to rank the nucleobase sensing performance. We study and rank the strength of interaction between four single DNA nucleotides (Adenine (A), Guanine (G), Cytosine (C), and Thymine (T)) on single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with acetone, ethanol, H2S and HCl. By sampling forward and reverse interaction paths, we compute the free-energy profiles of eight systems for the four targeted molecules. We find that dsDNA react differently than ssDNA to the targeted molecules, requiring more energy to move the molecule close to DNA as indicated by the potential of mean force (PMF). Comparing the PMF values of different systems, we obtain a relative ranking of DNA base for the detection of each molecule. Via the same procedure, we could generate a library of DNA sequences for the detection of a wide range of chemicals. A DNA sensor array built with selected sequences differentiating many disease biomarkers can be used in disease diagnosis and monitoring.

  11. Molecular Ecological Insights into Neotropical Bird-Tick Interactions.

    PubMed

    Miller, Matthew J; Esser, Helen J; Loaiza, Jose R; Herre, Edward Allen; Aguilar, Celestino; Quintero, Diomedes; Alvarez, Eric; Bermingham, Eldredge

    2016-01-01

    In the tropics, ticks parasitize many classes of vertebrate hosts. However, because many tropical tick species are only identifiable in the adult stage, and these adults usually parasitize mammals, most attention on the ecology of tick-host interactions has focused on mammalian hosts. In contrast, immature Neotropical ticks are often found on wild birds, yet difficulties in identifying immatures hinder studies of birds' role in tropical tick ecology and tick-borne disease transmission. In Panama, we found immature ticks on 227 out of 3,498 individually-sampled birds representing 93 host species (24% of the bird species sampled, and 13% of the Panamanian land bird fauna). Tick parasitism rates did not vary with rainfall or temperature, but did vary significantly with several host ecological traits. Likewise, Neotropical-Nearctic migratory birds were significantly less likely to be infested than resident species. Using a molecular library developed from morphologically-identified adult ticks specifically for this study, we identified eleven tick species parasitizing birds, indicating that a substantial portion of the Panamanian avian species pool is parasitized by a diversity of tick species. Tick species that most commonly parasitized birds had the widest diversity of avian hosts, suggesting that immature tick species are opportunistic bird parasites. Although certain avian ecological traits are positively associated with parasitism, we found no evidence that individual tick species show specificity to particular avian host ecological traits. Finally, our data suggest that the four principal vectors of Rocky Mountain Spotted Fever in the Neotropics rarely, if ever, parasitize Panamanian birds. However, other tick species that harbor newly-discovered rickettsial parasites of unknown pathogenicity are frequently found on these birds. Given our discovery of broad interaction between Panamanian tick and avian biodiversity, future work on tick ecology and the dynamics of

  12. Molecular Ecological Insights into Neotropical Bird–Tick Interactions

    PubMed Central

    Esser, Helen J.; Loaiza, Jose R.; Herre, Edward Allen; Aguilar, Celestino; Quintero, Diomedes; Alvarez, Eric; Bermingham, Eldredge

    2016-01-01

    In the tropics, ticks parasitize many classes of vertebrate hosts. However, because many tropical tick species are only identifiable in the adult stage, and these adults usually parasitize mammals, most attention on the ecology of tick-host interactions has focused on mammalian hosts. In contrast, immature Neotropical ticks are often found on wild birds, yet difficulties in identifying immatures hinder studies of birds’ role in tropical tick ecology and tick-borne disease transmission. In Panama, we found immature ticks on 227 out of 3,498 individually–sampled birds representing 93 host species (24% of the bird species sampled, and 13% of the Panamanian land bird fauna). Tick parasitism rates did not vary with rainfall or temperature, but did vary significantly with several host ecological traits. Likewise, Neotropical–Nearctic migratory birds were significantly less likely to be infested than resident species. Using a molecular library developed from morphologically–identified adult ticks specifically for this study, we identified eleven tick species parasitizing birds, indicating that a substantial portion of the Panamanian avian species pool is parasitized by a diversity of tick species. Tick species that most commonly parasitized birds had the widest diversity of avian hosts, suggesting that immature tick species are opportunistic bird parasites. Although certain avian ecological traits are positively associated with parasitism, we found no evidence that individual tick species show specificity to particular avian host ecological traits. Finally, our data suggest that the four principal vectors of Rocky Mountain Spotted Fever in the Neotropics rarely, if ever, parasitize Panamanian birds. However, other tick species that harbor newly–discovered rickettsial parasites of unknown pathogenicity are frequently found on these birds. Given our discovery of broad interaction between Panamanian tick and avian biodiversity, future work on tick ecology and the

  13. Interaction of proteases with legume seed inhibitors. Molecular features.

    PubMed

    de Seidl, D S

    1996-12-01

    After having found that raw black beans (Phaseolus vulgaris) were toxic, while the cooked ones constitute the basic diet of the underdeveloped peoples of the world, in the sixties, our research directed by Dr. Jaffé, concentrated mainly around the detection and identification of the heat labile toxic factors in legume seeds. A micromethod for the detection of protease inhibitors (PI) in individual seeds was developed, for the purpose of establishing that the multiple trypsin inhibitors (TI) found in the Cubagua variety were expressions of single seeds and not a mixture of a non homogenous bean lot. Six isoinhibitors were isolated and purified, all of which were "double-headed" and interacted with trypsin (T) and chymotrypsin (CHT) independently and simultaneously, as shown by electrophoresis of their binary and ternary complexes with each and both enzymes. However, their affinity for the enzymes, including elastases, was rather variable, as well as their amino acid composition which consisted of 51 units for inhibitor V, the smallest, and 83 amino acids for inhibitor I, the largest. A low molecular weight protein fraction that inhibited subtilisin (S), but recognized neither T, CHT nor pancreatic elastase was detected in 63 varieties of Phaseolus vulgaris as well as in broad beans (Vicia faba), chick peas (Cicer arietinum), jack beans (Canavalia ensiformis), kidney beans (Vigna aureus), etc., It was absent though, in soybeans (Glycine max), lentils (Lens culinaris), green peas (Pisum sativum), cowpea (Vigna sinensis) and lupine seeds (Lupinus sp). Subtilisin inhibitors (SI) were isolated from black beans, broad beans, chick peas and jack beans. Their Mr is between 8-9KD and they show a rather high stability in the presence of denaturing agents. They are specific toward microbial proteases, in addition to subtilisins, Carlsberg and BPN', they inhibit the alkaline protease from Tritirachium album (Protease K), from Aspergillus oryzae and one isolated from

  14. Molecular Ecological Insights into Neotropical Bird-Tick Interactions.

    PubMed

    Miller, Matthew J; Esser, Helen J; Loaiza, Jose R; Herre, Edward Allen; Aguilar, Celestino; Quintero, Diomedes; Alvarez, Eric; Bermingham, Eldredge

    2016-01-01

    In the tropics, ticks parasitize many classes of vertebrate hosts. However, because many tropical tick species are only identifiable in the adult stage, and these adults usually parasitize mammals, most attention on the ecology of tick-host interactions has focused on mammalian hosts. In contrast, immature Neotropical ticks are often found on wild birds, yet difficulties in identifying immatures hinder studies of birds' role in tropical tick ecology and tick-borne disease transmission. In Panama, we found immature ticks on 227 out of 3,498 individually-sampled birds representing 93 host species (24% of the bird species sampled, and 13% of the Panamanian land bird fauna). Tick parasitism rates did not vary with rainfall or temperature, but did vary significantly with several host ecological traits. Likewise, Neotropical-Nearctic migratory birds were significantly less likely to be infested than resident species. Using a molecular library developed from morphologically-identified adult ticks specifically for this study, we identified eleven tick species parasitizing birds, indicating that a substantial portion of the Panamanian avian species pool is parasitized by a diversity of tick species. Tick species that most commonly parasitized birds had the widest diversity of avian hosts, suggesting that immature tick species are opportunistic bird parasites. Although certain avian ecological traits are positively associated with parasitism, we found no evidence that individual tick species show specificity to particular avian host ecological traits. Finally, our data suggest that the four principal vectors of Rocky Mountain Spotted Fever in the Neotropics rarely, if ever, parasitize Panamanian birds. However, other tick species that harbor newly-discovered rickettsial parasites of unknown pathogenicity are frequently found on these birds. Given our discovery of broad interaction between Panamanian tick and avian biodiversity, future work on tick ecology and the dynamics of

  15. Molecular interactions of the neuronal GPI-anchored lipocalin Lazarillo.

    PubMed

    Sanchez, Diego; Ortega-Cubero, Sara; Akerström, Bo; Herrera, Macarena; Bastiani, Michael J; Ganfornina, Maria D

    2008-01-01

    Lazarillo, a glycoprotein involved in axon growth and guidance in the grasshopper embryo, is the only member of the lipocalin family that is attached to the cell surface by a GPI anchor. Recently, the study of Lazarillo homologous genes in Drosophila and mouse has revealed new functions in the regulation of lifespan, stress resistance and neurodegeneration. Here we report an analysis of biochemical properties of Lazarillo to gain insight into the molecular basis of its physiological function. Recombinant forms of the grasshopper protein were expressed in two different systems to test: (1) potential binding of several hydrophobic ligands; (2) protein-protein homophilic interactions; and (3) whether interaction with the function-blocking mAb 10E6 interferes with ligand binding. We tested 10 candidate ligands (retinoic acid, heme, bilirubin, biliverdin, ecdysterone, juvenile hormone, farnesol, arachidonic acid, linoleic acid and palmitic acid), and monitored binding using electrophoretic mobility shift, absorbance spectrum, and fluorimetry assays. Our work indicates binding to heme and retinoic acid, resulting in increased electrophoretic mobility, as well as to fatty acids, resulting in multimerization. Retinoic acid and fatty acids binding were confirmed by fluorescence titration, and heme binding was confirmed with absorbance spectrum assays. We demonstrate that Lazarillo oligomerizes in solution and can form clusters in the plasma membrane when expressed and GPI-anchored to the cell surface, however it is unable to mediate cell-cell adhesion. Finally, by ligand-mAb competition experiments we show that ligand-binding alone cannot be the key factor for Lazarillo to perform its function during axonal growth in the grasshopper embryo.

  16. Mechanical properties of borophene films: a reactive molecular dynamics investigation

    NASA Astrophysics Data System (ADS)

    Quy Le, Minh; Mortazavi, Bohayra; Rabczuk, Timon

    2016-11-01

    The most recent experimental advances could provide ways for the fabrication of several atomic thick and planar forms of boron atoms. For the first time, we explore the mechanical properties of five types of boron films with various vacancy ratios ranging from 0.1–0.15, using molecular dynamics simulations with ReaxFF force field. It is found that the Young’s modulus and tensile strength decrease with increasing the temperature. We found that boron sheets exhibit an anisotropic mechanical response due to the different arrangement of atoms along the armchair and zigzag directions. At room temperature, 2D Young’s modulus and fracture stress of these five sheets appear in the range 63–136 N m‑1 and 12–19 N m‑1, respectively. In addition, the strains at tensile strength are in the ranges of 9%–14%, 11%–19%, and 10%–16% at 1, 300, and 600 K, respectively. This investigation not only reveals the remarkable stiffness of 2D boron, but establishes relations between the mechanical properties of the boron sheets to the loading direction, temperature and atomic structures.

  17. Mechanical properties of borophene films: a reactive molecular dynamics investigation.

    PubMed

    Le, Minh Quy; Mortazavi, Bohayra; Rabczuk, Timon

    2016-11-01

    The most recent experimental advances could provide ways for the fabrication of several atomic thick and planar forms of boron atoms. For the first time, we explore the mechanical properties of five types of boron films with various vacancy ratios ranging from 0.1-0.15, using molecular dynamics simulations with ReaxFF force field. It is found that the Young's modulus and tensile strength decrease with increasing the temperature. We found that boron sheets exhibit an anisotropic mechanical response due to the different arrangement of atoms along the armchair and zigzag directions. At room temperature, 2D Young's modulus and fracture stress of these five sheets appear in the range 63-136 N m(-1) and 12-19 N m(-1), respectively. In addition, the strains at tensile strength are in the ranges of 9%-14%, 11%-19%, and 10%-16% at 1, 300, and 600 K, respectively. This investigation not only reveals the remarkable stiffness of 2D boron, but establishes relations between the mechanical properties of the boron sheets to the loading direction, temperature and atomic structures. PMID:27678335

  18. Molecular dynamics simulation investigations of atomic-scale wear

    NASA Astrophysics Data System (ADS)

    Shao, Yuchong; Falk, Michael

    2013-03-01

    Frictional running-in and material transfer in wear take place at the micro- and nano-scale but the fundamental physics remain poorly understood. Here we intend to investigate wear and running-in phenomena in silicon based materials, which are widely utilized in micro/nano electromechanical systems(MEMS/NEMS). We use an atomic force microscopy (AFM) model composed of a crystalline silicon tip and substrate coated with native oxide layers. Molecular dynamics simulation has been performed over a range of temperatures, external loads and slip rates. Results show that adhesive wear takes place across the interface in an atom-by-atom fashion which remodels the tip leading to a final steady state. We quantify the rate of material transfer as a function of the coverage of non-bridging oxygen (NBO) atoms, which has a pronounced change of the system's tribological and wear behaviors. A constitutive rate and state model is proposed to predict the evolution of frictional strength and wear. This work is supported by the National Science Foundation under Award No. 0926111.

  19. Mechanical properties of borophene films: a reactive molecular dynamics investigation.

    PubMed

    Le, Minh Quy; Mortazavi, Bohayra; Rabczuk, Timon

    2016-11-01

    The most recent experimental advances could provide ways for the fabrication of several atomic thick and planar forms of boron atoms. For the first time, we explore the mechanical properties of five types of boron films with various vacancy ratios ranging from 0.1-0.15, using molecular dynamics simulations with ReaxFF force field. It is found that the Young's modulus and tensile strength decrease with increasing the temperature. We found that boron sheets exhibit an anisotropic mechanical response due to the different arrangement of atoms along the armchair and zigzag directions. At room temperature, 2D Young's modulus and fracture stress of these five sheets appear in the range 63-136 N m(-1) and 12-19 N m(-1), respectively. In addition, the strains at tensile strength are in the ranges of 9%-14%, 11%-19%, and 10%-16% at 1, 300, and 600 K, respectively. This investigation not only reveals the remarkable stiffness of 2D boron, but establishes relations between the mechanical properties of the boron sheets to the loading direction, temperature and atomic structures.

  20. Novel Genetic and Molecular Tools for the Investigation and Control of Dengue Virus Transmission by Mosquitoes.

    PubMed

    Franz, Alexander W E; Clem, Rollie J; Passarelli, A Lorena

    2014-03-01

    Aedes aegypti is the principal vector of dengue virus (DENV) throughout the tropical world. This anthropophilic mosquito species needs to be persistently infected with DENV before it can transmit the virus through its saliva to a new vertebrate host. In the mosquito, DENV is confronted with several innate immune pathways, among which RNA interference is considered the most important. The Ae. aegypti genome project opened the doors for advanced molecular studies on pathogen-vector interactions including genetic manipulation of the vector for basic research and vector control purposes. Thus, Ae. aegypti has become the primary model for studying vector competence for arboviruses at the molecular level. Here, we present recent findings regarding DENV-mosquito interactions, emphasizing how innate immune responses modulate DENV infections in Ae. aegypti. We also describe the latest advancements in genetic manipulation of Ae. aegypti and discuss how this technology can be used to investigate vector transmission of DENV at the molecular level and to control transmission of the virus in the field.

  1. Prediction of drug-packaging interactions via molecular dynamics (MD) simulations.

    PubMed

    Feenstra, Peter; Brunsteiner, Michael; Khinast, Johannes

    2012-07-15

    The interaction between packaging materials and drug products is an important issue for the pharmaceutical industry, since during manufacturing, processing and storage a drug product is continuously exposed to various packaging materials. The experimental investigation of a great variety of different packaging material-drug product combinations in terms of efficacy and safety can be a costly and time-consuming task. In our work we used molecular dynamics (MD) simulations in order to evaluate the applicability of such methods to pre-screening of the packaging material-solute compatibility. The solvation free energy and the free energy of adsorption of diverse solute/solvent/solid systems were estimated. The results of our simulations agree with experimental values previously published in the literature, which indicates that the methods in question can be used to semi-quantitatively reproduce the solid-liquid interactions of the investigated systems.

  2. Interaction of diuron to human serum albumin: Insights from spectroscopic and molecular docking studies.

    PubMed

    Chen, Huilun; Rao, Honghao; Yang, Jian; Qiao, Yongxiang; Wang, Fei; Yao, Jun

    2016-01-01

    This investigation was undertaken to determine the interaction of diuron with human serum albumin (HSA) was studied by monitoring the spectral behavior of diuron-HSA system. The fluorescence of HSA at 340 nm excited at 230 nm was obviously quenched by diuron due to dynamic collision and the quenching constant was of the order of 10(4) L mol(-1) at 310 K. However, no fluorescence quenching was observed when excited at 280 nm. Thermodynamic investigations revealed that the combination between diuron and HSA was entropy driven by predominantly hydrophobic interactions. The binding of diuron induced the drastic reduction in α-helix conformation and the significant enhancement in β-turn conformation of HSA. In addition, both sites marker competition study and molecular modeling simulation evidenced the binding of diuron to HSA primarily took place in subdomain IIIA (Sudlow's site II). PMID:26671830

  3. Investigating the correlations among the chemical structures, bioactivity profiles and molecular targets of small molecules

    PubMed Central

    Cheng, Tiejun; Wang, Yanli; Bryant, Stephen H.

    2010-01-01

    Motivation: Most of the previous data mining studies based on the NCI-60 dataset, due to its intrinsic cell-based nature, can hardly provide insights into the molecular targets for screened compounds. On the other hand, the abundant information of the compound–target associations in PubChem can offer extensive experimental evidence of molecular targets for tested compounds. Therefore, by taking advantages of the data from both public repositories, one may investigate the correlations between the bioactivity profiles of small molecules from the NCI-60 dataset (cellular level) and their patterns of interactions with relevant protein targets from PubChem (molecular level) simultaneously. Results: We investigated a set of 37 small molecules by providing links among their bioactivity profiles, protein targets and chemical structures. Hierarchical clustering of compounds was carried out based on their bioactivity profiles. We found that compounds were clustered into groups with similar mode of actions, which strongly correlated with chemical structures. Furthermore, we observed that compounds similar in bioactivity profiles also shared similar patterns of interactions with relevant protein targets, especially when chemical structures were related. The current work presents a new strategy for combining and data mining the NCI-60 dataset and PubChem. This analysis shows that bioactivity profile comparison can provide insights into the mode of actions at the molecular level, thus will facilitate the knowledge-based discovery of novel compounds with desired pharmacological properties. Availability: The bioactivity profiling data and the target annotation information are publicly available in the PubChem BioAssay database (ftp://ftp.ncbi.nlm.nih.gov/pubchem/Bioassay/). Contact: ywang@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.gov Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20947527

  4. Experimental and theoretical investigation on the interaction between cyclovirobuxine D and human serum albumin

    NASA Astrophysics Data System (ADS)

    Yue, Yuanyuan; Liu, Ren; Liu, Jianming; Dong, Qiao; Fan, Jing

    2014-07-01

    Cyclovirobuxine D is an active compound extracted from the plant Buxux microphylla, and widely available as medications; however, its abuse may casts potential detrimental effects on human health. By using multispectroscopic techniques and molecular modeling, the interaction of cyclovirobuxine D with human serum albumin was investigated. The fluorescence results manifested that static type was the operative mechanism for the interaction with human serum albumin. The structural investigation of the complexed HSA through CD, three-dimensional, FT-IR and synchronous fluorescence shown the polypeptide chain of HSA partially destabilizing. Docking studies revealed the molecule to be bound in the subdomain IIA. Finally, we investigated the distance between the bound ligand and Trp-214 of human serum albumin.

  5. 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. PMID:25311860

  6. Molecular Interactions Between Alcohols and Metal Phthalocyanine Thin Films for Optical Gas Sensor Applications

    NASA Astrophysics Data System (ADS)

    Uttiya, Sureeporn; Kladsomboon, Sumana; Chamlek, Onanong; Suwannet, Wiriya; Osotchan, Tanakorn; Kerdcharoen, Teerakiat; Brinkmann, Martin; Pratontep, Sirapat

    Optically active organic gas sensors represent a promising molecular sensing device with low power consumption. We report experimental and computational investigations into the molecular interactions of metal phthalocyanine thin films with alcohol vapor. In the gas-sensing regime, the interactions of zinc phthalocyanine and alcohol molecules were studied by the Density Functional Theory (DFT) calculations, in comparison to the x-ray absorption spectroscopy. The DFT results reveal a reversible charge interaction mechanism between the zinc atom and the oxygen atom in the alcohol OH group, which corresponds to a shift in the x-ray absorption edge of the zinc atom. In the irreversible interaction regime, the effect of saturated alcohol vapor on spin-coated zinc phthalocyanine films was studied by the phase contrast microscopy, the optical absorption spectroscopy, and the transmission electron microscopy. Annealing the spin-coated films in saturated methanol vapor was found to induce an irreversible structural transformation from an amorphous to a crystalline phase, similar to the effect of a thermal annealing process. These crystallization processes of the zinc phthalocyanine films were also found to enhance their stability and alcohol sensing performance.

  7. Interaction of glutathione with bovine serum albumin: Spectroscopy and molecular docking.

    PubMed

    Jahanban-Esfahlan, Ali; Panahi-Azar, Vahid

    2016-07-01

    This study aims to investigate the interaction between glutathione and bovine serum albumin (BSA) using ultraviolet-visible (UV-vis) absorption, fluorescence spectroscopies under simulated physiological conditions (pH 7.4) and molecular docking methods. The results of fluorescence spectroscopy indicated that the fluorescence intensity of BSA was decreased considerably upon the addition of glutathione through a static quenching mechanism. The fluorescence quenching obtained was related to the formation of BSA-glutathione complex. The values of KSV, Ka and Kb for the glutathione and BSA interaction were in the order of 10(5). The thermodynamic parameters including enthalpy change (ΔH), entropy change (ΔS) and also Gibb's free energy (ΔG) were determined using Van't Hoff equation. These values showed that hydrogen bonding and van der Waals forces were the main interactions in the binding of glutathione to BSA and the stabilization of the complex. Also, the interaction of glutathione and BSA was spontaneous. The effects of glutathione on the BSA conformation were determined using UV-vis spectroscopy. Moreover, glutathione was docked in BSA using ArgusLab as a molecular docking program. It was recognized that glutathione binds within the sub-domain IIA pocket in domain II of BSA. PMID:26920314

  8. Molecular dynamics simulation of the interactions between EHD1 EH domain and multiple peptides* #

    PubMed Central

    Yu, Hua; Wang, Mao-Jun; Xuan, Nan-Xia; Shang, Zhi-Cai; Wu, Jun

    2015-01-01

    Objective: To provide essential information for peptide inhibitor design, the interactions of Eps15 homology domain of Eps15 homology domain-containing protein 1 (EHD1 EH domain) with three peptides containing NPF (asparagine-proline-phenylalanine), DPF (aspartic acid-proline-phenylalanine), and GPF (glycine-proline-phenylalanine) motifs were deciphered at the atomic level. The binding affinities and the underlying structure basis were investigated. Methods: Molecular dynamics (MD) simulations were performed on EHD1 EH domain/peptide complexes for 60 ns using the GROMACS package. The binding free energies were calculated and decomposed by molecular mechanics/generalized Born surface area (MM/GBSA) method using the AMBER package. The alanine scanning was performed to evaluate the binding hot spot residues using FoldX software. Results: The different binding affinities for the three peptides were affected dominantly by van der Waals interactions. Intermolecular hydrogen bonds provide the structural basis of contributions of van der Waals interactions of the flanking residues to the binding. Conclusions: van der Waals interactions should be the main consideration when we design peptide inhibitors of EHD1 EH domain with high affinities. The ability to form intermolecular hydrogen bonds with protein residues can be used as the factor for choosing the flanking residues. PMID:26465136

  9. Tuning the size and optical properties in molecular nano/microcrystals: manifestation of hierarchical interactions.

    PubMed

    Patra, A; Hebalkar, N; Sreedhar, B; Sarkar, M; Samanta, A; Radhakrishnan, T P

    2006-05-01

    Intermolecular interactions, such as hydrogen bonding, dipolar and van der Waals, occurring in molecular crystals cover a range of magnitudes. As the crystal evolves from a relatively softer state in the nanoscopic size regime to a harder one in the microcrystalline and bulk solid state, the impact of the hierarchy of intermolecular interactions can be expected to emerge in a progressive fashion. The strongest interactions alone would be manifested at small sizes; as the crystal grows, the effect of the weaker ones will be added on, with the bulk crystals exhibiting the cumulative impact of the different interactions. We demonstrate this phenomenon through investigations of the solution, colloid, and solid state of a novel zwitterionic molecule based on the diaminodicyanoquinodimethane framework. A reprecipitation-digestion protocol is developed for the fabrication of nano/microcrystals of varying sizes. Microscopic and spectroscopic characterizations reveal tuning of the size and optical properties of this material. The optical absorption of the colloidal particles evolves with size towards that of the bulk solid, the emission showing a steady enhancement of intensity. Crystallographic investigations coupled with semiempirical computations provide a viable model to describe the range of observations in terms of the gradual accumulation of hierarchical intermolecular interactions.

  10. Interactions between polymers and single-walled boron nitride nanotubes: a molecular dynamics simulation approach.

    PubMed

    Nasrabadi, Amir Taghavi; Foroutan, Masumeh

    2010-12-01

    In this work, we used a molecular dynamics (MD) simulation approach to investigate the interfacial binding of boron nitride nanotubes (BNNTs) with poly[m-phenylenevinylene-co-(2,5-dioctyloxy-p-phenylenevinylene)] (PmPV), polystyrene (PS), and polythiophene (PT). Quantum partial charges of BNNT-polymer composites were determined by density functional theory (DFT) calculations and then included in MD simulations. The interaction energy between nanotubes and polymer molecules was computed, and the morphology of polymers stacked onto the surface of the nanotubes was investigated based on the dihedral angle (θ). Our results confirm that the interaction energy is strongly influenced by the specific monomer structure of polymer and nanotube radius, but the influence of temperature is likely negligible. Among the investigated polymers, PT possesses the strongest adhesion to the BNNTs, followed by PmPV and PS. Moreover, the comparison of our results for BNNT-polymer composities with those of the similar carbon nanotube (CNT)-polymer composites reveals that the BNNT-polymer interactions are much stronger, which is the most important result of this work. This finding is also in good agreement with recent experimental observations. The higher values of interaction energy of BNNT-polymer composites suggest that the BNNTs could be more efficient nanofillers than the CNTs for nanocomposite reinforcement applications.

  11. Investigation of Syngas Interaction in Alcohol Synthesis Catalysts

    SciTech Connect

    1997-09-01

    This report presents the work done on Investigation of Syngas Interaction in Alcohol Synthesis Catalysts during the last quarter. FTIR absorption studies on Cu/Co/Cr catalysts using CO as a probe molecule are presented in this report. The aim of this study is to investigate the nature of infrared adsorption of CO on copper-cobalt-chromia catalysts. The chemisorption of CO on metal particles can be associative/dissociative depending upon the nature of the metal, the type of exposed faces and adsorption temperature. Several investigators [1-3], classified cobalt as a border line element which under particular conditions can dissociate CO. For instance the (0001) face of CO is known to be inactive for CO dissociation at room temperature, while the stepped (1012) face is active at very moderate temperatures [4-5] with formation of surface carbide. Of the dissociated species carbon could form a surface carbide and simultaneously the oxygen could form a surface oxide.

  12. Optoelectronic investigation of nanodiamond interactions with human blood

    NASA Astrophysics Data System (ADS)

    Ficek, M.; Wróbel, M. S.; Wasowicz, M.; Jedrzejewska-Szczerska, M.

    2016-03-01

    We present optoelectronic investigation of in vitro interactions of whole human blood with different nanodiamond biomarkers. Plasmo-chemical modifications of detonation nanodiamond particles gives the possibility for controlling their surface for biological applications. Optical investigations reveal the biological activity of nanodiamonds in blood dependent on its surface termination. We compare different types of nanodiamonds: commercial non-modified detonation nanodiamonds, and nanodiamonds modified by MW PACVD method with H2-termination, and chemically modified nanodiamond with O2-termination. The absorption spectra, and optical microscope investigations were conducted. The results indicate haemocompatibility of non-modified detonation nanodiamond as well as modified nanodiamonds, which enables their application for drug delivery, as well as sensing applications.

  13. Experimental investigation of the piano hammer-string interaction.

    PubMed

    Birkett, Stephen

    2013-04-01

    Experimental techniques for investigating the piano hammer-string interaction are described. It is argued that the accuracy, consistency, and scope of conclusions of previous studies can be compromised by limitations of the conventional methods relating to key inputs; physical distortion; numerical distortion, particularly when differentiation or integration of measured signals is used to derive primary response variables; contact identification; and synchronization issues. These problems are discussed, and experimental methods that have been devised to avoid them are described and illustrated by detailed results from a study of the hammer-string interaction in a vertical piano. High resolution displacements are obtained directly by non-contact high-speed imaging and quantitative motion tracking. The attention focused on achieving very accurate and consistent temporal and spatial alignment, including the objective procedure used for contact identification, allows meaningful comparisons of responses from separate tests. String motion at the strike point and on each side of it, as well as hammer motion, is obtained for eight dynamic levels from 1.06 to 2.98 m/s impact velocity. Detailed observations of the force-compression behavior of the hammer interacting with real strings are presented. The direct effects of hammer shank deflection and agraffe string pulses on the interaction are also highlighted. PMID:23556611

  14. Experimental investigation of the piano hammer-string interaction.

    PubMed

    Birkett, Stephen

    2013-04-01

    Experimental techniques for investigating the piano hammer-string interaction are described. It is argued that the accuracy, consistency, and scope of conclusions of previous studies can be compromised by limitations of the conventional methods relating to key inputs; physical distortion; numerical distortion, particularly when differentiation or integration of measured signals is used to derive primary response variables; contact identification; and synchronization issues. These problems are discussed, and experimental methods that have been devised to avoid them are described and illustrated by detailed results from a study of the hammer-string interaction in a vertical piano. High resolution displacements are obtained directly by non-contact high-speed imaging and quantitative motion tracking. The attention focused on achieving very accurate and consistent temporal and spatial alignment, including the objective procedure used for contact identification, allows meaningful comparisons of responses from separate tests. String motion at the strike point and on each side of it, as well as hammer motion, is obtained for eight dynamic levels from 1.06 to 2.98 m/s impact velocity. Detailed observations of the force-compression behavior of the hammer interacting with real strings are presented. The direct effects of hammer shank deflection and agraffe string pulses on the interaction are also highlighted.

  15. Experimental investigation of interaction processes between droplets and hot walls

    NASA Astrophysics Data System (ADS)

    Karl, A.; Frohn, A.

    2000-04-01

    A detailed experimental investigation of interaction processes of small liquid droplets with hot walls well above the Leidenfrost temperature has been carried out. The experimental method which uses monodisperse droplet streams in combination with a standard video camera allows very detailed observations and measurements with very high time resolution. The main intent of this paper is to study the mechanical behavior of liquid droplets impacting on hot walls well above the Leidenfrost temperature. A better understanding of this process may lead to a better modeling of two-phase flows, especially for applications in fuel preparation processes, combustion processes, and spray cooling. The loss of momentum of the droplets, the droplet deformation, and the onset of droplet disintegration have been investigated. For all experimental results correlations have been developed, which can be used to improve the numerical modeling of two-phase flows. Using the correlation for the loss of momentum a theoretical approximation for the maximum droplet deformation has been deduced, which yields a very good agreement with our own measurements as well as with results reported in the literature. A minimum impinging angle for droplet disintegration has been discovered for small impinging angles. Below this impinging angle no droplet disintegration is observed. This phenomenon is directly related to the energy dissipation at the wall during the interaction process. With the presented work the understanding of basic interaction processes between droplets and hot walls may be improved.

  16. Specific interactions between amyloid-β peptide and curcumin derivatives: Ab initio molecular simulations

    NASA Astrophysics Data System (ADS)

    Ishimura, Hiromi; Kadoya, Ryushi; Suzuki, Tomoya; Murakawa, Takeru; Shulga, Sergiy; Kurita, Noriyuki

    2015-07-01

    Alzheimer's disease is caused by accumulation of amyloid-β (Aβ) peptides in a brain. To suppress the production of Aβ peptides, it is effective to inhibit the cleavage of amyloid precursor protein (APP) by secretases. However, because the secretases also play important roles to produce vital proteins for human body, inhibitors for the secretases may have side effects. To propose new agents for protecting the cleavage site of APP from the attacking of the γ-secretase, we have investigated here the specific interactions between a short APP peptide and curcumin derivatives, using protein-ligand docking as well as ab initio molecular simulations.

  17. Molecular weight control in organochromium olefin polymerization catalysis by hemilabile ligand-metal interactions.

    PubMed

    Mark, Stefan; Wadepohl, Hubert; Enders, Markus

    2016-01-01

    A series of Cr(III) complexes based on quinoline-cyclopentadienyl ligands with additional hemilabile side arms were prepared and used as single-site catalyst precursors for ethylene polymerization. The additional donor functions interact with the metal centers only after activation with the co-catalyst. Evidence for this comes from DFT-calculations and from the differing behavior of the complexes in ethylene polymerization. All complexes investigated show very high catalytic activity and the additional side arm minimizes chain-transfer reactions, leading to increase of molecular weights of the resulting polymers. PMID:27559387

  18. Phonon-magnon interactions in BCC iron: A combined molecular and spin dynamics study

    SciTech Connect

    Perera, Meewanage Dilina N; Landau, David P; Nicholson, Don M; Stocks, George Malcolm; Eisenbach, Markus; Yin, Junqi; Brown, Greg

    2014-01-01

    Combining an atomistic many-body potential with a classical spin Hamiltonian pa- rameterized by first principles calculations, molecular-spin dynamics computer sim- ulations were performed to investigate phonon-magnon interactions in BCC iron. Results obtained for spin-spin and density-density dynamic structure factors show that noticeable softening and damping of magnon modes occur due to the presence of lattice vibrations. Furthermore, as a result of the phonon-magnon coupling, addi- tional longitudinal spin wave excitations are observed, with the same frequencies as the longitudinal phonon modes.

  19. Molecular weight control in organochromium olefin polymerization catalysis by hemilabile ligand–metal interactions

    PubMed Central

    Mark, Stefan; Wadepohl, Hubert

    2016-01-01

    Summary A series of Cr(III) complexes based on quinoline-cyclopentadienyl ligands with additional hemilabile side arms were prepared and used as single-site catalyst precursors for ethylene polymerization. The additional donor functions interact with the metal centers only after activation with the co-catalyst. Evidence for this comes from DFT-calculations and from the differing behavior of the complexes in ethylene polymerization. All complexes investigated show very high catalytic activity and the additional side arm minimizes chain-transfer reactions, leading to increase of molecular weights of the resulting polymers. PMID:27559387

  20. Phonon-magnon interactions in body centered cubic iron: A combined molecular and spin dynamics study

    SciTech Connect

    Perera, Dilina Landau, David P.; Nicholson, Don M.; Malcolm Stocks, G.; Eisenbach, Markus; Yin, Junqi; Brown, Gregory

    2014-05-07

    Combining an atomistic many-body potential with a classical spin Hamiltonian parameterized by first principles calculations, molecular-spin dynamics computer simulations were performed to investigate phonon-magnon interactions in body centered cubic iron. Results obtained for spin-spin and density-density dynamic structure factors show that noticeable softening and damping of magnon modes occur due to the presence of lattice vibrations. Furthermore, as a result of the phonon-magnon coupling, additional longitudinal spin wave excitations are observed, with the same frequencies as the longitudinal phonon modes.

  1. High-resolution single-molecule recognition imaging of the molecular details of ricin-aptamer interaction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The molecular details of DNA aptamer-ricin interactions were investigated. The toxic protein ricin molecules were immobilized on Au(111) surface using N-hydroxysuccinimide (NHS) ester to specifically react with lysine residues located on the ricin B chains. A single ricin molecule was visualized in ...

  2. Interactions of acidic pharmaceuticals with human serum albumin: insights into the molecular toxicity of emerging pollutants.

    PubMed

    Chen, Jiabin; Zhou, Xuefei; Zhang, Yalei; Qian, Yajie; Gao, Haiping

    2012-10-01

    Acidic pharmaceuticals such as diclofenac (DCF), clofibric acid (CA) and ketoprofen (KTP) have been detected frequently in environmental media. In order to reveal the toxicity of such emerging pollutants, their interactions with human serum albumin (HSA) were investigated by capillary electrophoresis, molecular spectrometry, and equilibrium dialysis. The binding constants and sites of these acidic pharmaceuticals with HSA were obtained. The thermodynamic parameters, e.g. enthalpy change and entropy change of these interactions were calculated to characterize that all the reactions resulted from hydrophobic and electrostatic interactions. The static quenching of the fluorescence of HSA was observed when interacted with acidic pharmaceuticals, indicating acidic pharmaceuticals bound to Tryptophan residue of HSA. The 3D fluorescence and circular dichroism confirmed that the secondary conformation of HSA changed after the interactions with the pharmaceuticals. At physiological condition, only 0.12 mM acidic pharmaceuticals reduced the binding of vitamin B(2) to HSA by 37, 30 and 21% for DCF, KTP and CA, respectively. This work provides an insight into non-covalent interactions between emerging contaminants and biomolecule, and is helpful for clarifying the toxic mechanism of such emerging contaminants. PMID:22307229

  3. Solvent- and concentration-dependent molecular interactions of taxol (Paclitaxel).

    PubMed

    Balasubramanian, S V; Alderfer, J L; Straubinger, R M

    1994-10-01

    Taxol (paclitaxel) is a promising anticancer agent that has been approved for the treatment of ovarian cancer and is under investigation for the therapy of other tumors. Paclitaxel is poorly soluble in water, and information on its physical behavior in hydrophilic and hydrophobic environments is limited. Circular dichroism (CD) and nuclear magnetic resonance spectroscopy were used to investigate the effect of solvent and drug concentration on the solution conformation of paclitaxel. CD is sensitive to paclitaxel's environment, owing to the presence of effective chromophores in the vicinity of several chiral centers. It was found that (i) the conformation of the paclitaxel side chain depends on the polarity of the solvent and (ii) paclitaxel has a tendency to undergo concentration-dependent aggregation in solvents such as chloroform. To account for the observations, a model is proposed in which paclitaxel molecules are held together in stacks by intermolecular hydrogen bonds involving all four exchangeable protons. Intermolecular interactions and self-association of paclitaxel may have impact not only on the physical stability of the drug in existing formulations or investigational vehicles but also on the effect of paclitaxel in the stabilization of cellular microtubules.

  4. Molecular Modeling and Experimental Investigations of Nonlinear Optical Compounds Monosubstituted Derivatives of Dicyanovinylbenzene

    NASA Technical Reports Server (NTRS)

    Timofeeva, Tatiana V.; Nesterov, Vladimir N.; Antipin, Mikhail Yu.; Clark, Ronald D.; Sanghadasa, Mohan; Cardelino, Beatriz H.; Moore, Craig E.; Frazier, Donald O.

    1999-01-01

    A search for potential nonlinear optical compounds was performed using the Cambridge Structure Database and molecular modeling. We investigated a series of monosubstituted derivatives of dicyanovinylbenzene, since the nonlinear optical (NLO) properties of such derivatives (o-methoxy-dicyanovinylbenzene, DIVA) were studied earlier. The molecular geometry of these compounds was investigated with x-ray analysis and discussed along with the results of molecular mechanics and ab initio quantum chemical calculations. The influence of crystal packing on the planarity of the molecules of this series has been revealed. Two new compounds from the series studied, ortho-F and para-Cl-dicyanovinylbenzene, according to powder measurements, were found to be NLO compounds in the crystal state about 10 times more active than urea. The peculiarities of crystal structure formation in the framework of balance between van der Waals and electrostatic interactions have been discussed. The crystal shape of DIVA and two new NLO compounds have been calculated on the basis of the known crystal structure.

  5. Ochratoxin A: Molecular Interactions, Mechanisms of Toxicity and Prevention at the Molecular Level.

    PubMed

    Kőszegi, Tamás; Poór, Miklós

    2016-04-01

    Ochratoxin A (OTA) is a widely-spread mycotoxin all over the world causing major health risks. The focus of the present review is on the molecular and cellular interactions of OTA. In order to get better insight into the mechanism of its toxicity and on the several attempts made for prevention or attenuation of its toxic action, a detailed description is given on chemistry and toxicokinetics of this mycotoxin. The mode of action of OTA is not clearly understood yet, and seems to be very complex. Inhibition of protein synthesis and energy production, induction of oxidative stress, DNA adduct formation, as well as apoptosis/necrosis and cell cycle arrest are possibly involved in its toxic action. Since OTA binds very strongly to human and animal albumin, a major emphasis is done regarding OTA-albumin interaction. Displacement of OTA from albumin by drugs and by natural flavonoids are discussed in detail, hypothesizing their potentially beneficial effect in order to prevent or attenuate the OTA-induced toxic consequences. PMID:27092524

  6. Ochratoxin A: Molecular Interactions, Mechanisms of Toxicity and Prevention at the Molecular Level

    PubMed Central

    Kőszegi, Tamás; Poór, Miklós

    2016-01-01

    Ochratoxin A (OTA) is a widely-spread mycotoxin all over the world causing major health risks. The focus of the present review is on the molecular and cellular interactions of OTA. In order to get better insight into the mechanism of its toxicity and on the several attempts made for prevention or attenuation of its toxic action, a detailed description is given on chemistry and toxicokinetics of this mycotoxin. The mode of action of OTA is not clearly understood yet, and seems to be very complex. Inhibition of protein synthesis and energy production, induction of oxidative stress, DNA adduct formation, as well as apoptosis/necrosis and cell cycle arrest are possibly involved in its toxic action. Since OTA binds very strongly to human and animal albumin, a major emphasis is done regarding OTA-albumin interaction. Displacement of OTA from albumin by drugs and by natural flavonoids are discussed in detail, hypothesizing their potentially beneficial effect in order to prevent or attenuate the OTA-induced toxic consequences. PMID:27092524

  7. Matrix metalloproteinase expression and molecular interaction network analysis in gastric cancer

    PubMed Central

    Xu, Jianting; E, Changyong; Yao, Yongfang; Ren, Shuangchun; Wang, Guoqing; Jin, Haofan

    2016-01-01

    Gastric cancer (GC) is one of the most common types of cancer of the digestive tract. Invasion of tumor cells into surrounding tissue and metastasis are among the most significant checkpoints in tumor progression. It is known that matrix metalloproteinases (MMPs) are involved in these processes; however, knowledge of their molecular interaction networks is still limited. Investigation of these networks could provide a more comprehensive picture of the function of MMPs in tumorigenesis. Furthermore, it could be used to develop new approaches to targeted anticancer therapy. In this study, we performed microarray analysis, and 1666 genes that were aberrantly expressed in GC tissues were identified (fold change >2, P<0.05). In addition, quantitative polymerase chain reaction analysis has confirmed that MMP1, MMP3, MMP7, MMP10, MMP11 and MMP12 expression is upregulated in GC. In addition, the MMP3 expression level was negatively correlated with GC differentiation (P<0.05). By integrating the microarray information and BioGRID and STRING databases, we constructed an MMP-related molecular interaction network and observed that 18 genes (including MMPs) were highly expressed in GC tissues. The most enriched of these 18 genes in the Gene Oncology (GO) and pathway analysis were in extracellular matrix disassembly (GO biological process) and extracellular matrix-receptor interaction (KEGG pathway), which are closely correlated with cancer invasion and metastasis. Collectively, our results suggest that the MMP-related interaction network has a role in GC progression, and therefore further studies are required in order to investigate these network interactions in tumorigenesis. PMID:27698806

  8. Matrix metalloproteinase expression and molecular interaction network analysis in gastric cancer

    PubMed Central

    Xu, Jianting; E, Changyong; Yao, Yongfang; Ren, Shuangchun; Wang, Guoqing; Jin, Haofan

    2016-01-01

    Gastric cancer (GC) is one of the most common types of cancer of the digestive tract. Invasion of tumor cells into surrounding tissue and metastasis are among the most significant checkpoints in tumor progression. It is known that matrix metalloproteinases (MMPs) are involved in these processes; however, knowledge of their molecular interaction networks is still limited. Investigation of these networks could provide a more comprehensive picture of the function of MMPs in tumorigenesis. Furthermore, it could be used to develop new approaches to targeted anticancer therapy. In this study, we performed microarray analysis, and 1666 genes that were aberrantly expressed in GC tissues were identified (fold change >2, P<0.05). In addition, quantitative polymerase chain reaction analysis has confirmed that MMP1, MMP3, MMP7, MMP10, MMP11 and MMP12 expression is upregulated in GC. In addition, the MMP3 expression level was negatively correlated with GC differentiation (P<0.05). By integrating the microarray information and BioGRID and STRING databases, we constructed an MMP-related molecular interaction network and observed that 18 genes (including MMPs) were highly expressed in GC tissues. The most enriched of these 18 genes in the Gene Oncology (GO) and pathway analysis were in extracellular matrix disassembly (GO biological process) and extracellular matrix-receptor interaction (KEGG pathway), which are closely correlated with cancer invasion and metastasis. Collectively, our results suggest that the MMP-related interaction network has a role in GC progression, and therefore further studies are required in order to investigate these network interactions in tumorigenesis.

  9. Molecular interactions between dimethoxycurcumin and Pamam dendrimer carriers.

    PubMed

    Markatou, Eleni; Gionis, Vassilis; Chryssikos, Georgios D; Hatziantoniou, Sophia; Georgopoulos, Aristidis; Demetzos, Costas

    2007-07-18

    Dimethoxycurcumin, a lipophilic analog of curcumin found as a major pigment in the Indian species turmeric (Curcuma longa Linn.), is known to possess significant activity against various cancer cell lines, but its use as an anticancer drug is hindered by its poor water solubility. The conjugation of dimethoxycurcumin to water-soluble PAMAM dendrimers (generations 3.5 and 4) is demonstrated. The maximum drug-dendrimer incorporation efficiency is 4.3 and 5.0 molar for G3.5 and G4, respectively. The FTIR-ATR investigation of the neat compounds and the drug-dendrimer systems indicate that dimethoxycurcumin is in the enolic form, while its interaction with the integer generation dendrimer involves the major conformational change of the terminal ethylene amine groups. PMID:17428628

  10. Understanding Molecular Interactions within Chemically Selective Layered Polymer Assemblies

    SciTech Connect

    Gary J. Blanchard

    2009-06-30

    This work focuses on two broad issues. These are (1) the molecular origin of the chemical selectivity achieved with ultrathin polymer multilayers, and (2) how the viscoelastic properties of the polymer layers are affected by exposure to solvent and analytes. These issues are inter-related, and to understand them we need to design experiments that probe both the energetic and kinetic aspects of interfacial adsorption processes. This project focuses on controling the chemical structure, thickness, morphology and sequential ordering of polymer layers bound to interfaces using maleimide-vinyl ether and closely related alternating copolymerization chemistry and efficient covalent cross-linking reactions that allow for layer-by-layer polymer deposition. This chemistry has been developed during the funding cycle of this Grant. We have measure the equilibrium constants for interactions between specific layers within the polymer interfaces and size-controlled, surface-functionalized gold nanoparticles. The ability to control both size and functionality of gold nanoparticle model analytes allows us to evaluate the average “pore size” that characterizes our polymer films. We have measured the “bulk” viscosity and shear modulus of the ultrathin polymer films as a function of solvent overlayer identity using quartz crystal microbalance complex impedance measurements. We have measured microscopic viscosity at specific locations within the layered polymer interfaces with time-resolved fluorescence lifetime and depolarization techniques. We combine polymer, cross-linking and nanoparticle synthetic expertise with a host of characterization techniques, including QCM gravimetry and complex impedance analysis, steady state and time-resolved spectroscopies.

  11. Raman probing of molecular interactions of alginate biopolymers with cells

    NASA Astrophysics Data System (ADS)

    Chourpa, Igor; Carpentier, Philippe; Maingault, Philippe; Fetissoff, Franck; Dubois, Pierre

    2000-05-01

    The biological polymers extracted from brown algae, alginates, are novel materials in biotechnology and biomedicine. Their ability to form viscous gels is used to immobilize or encapsulate yeast, enzymes, living cells and drugs. Calcium-alginate fibers are extensively used in wound dressings since exhibit antihaemostatic and healing properties. The problem with alginate-made dressings in surgery is their slow biodegradability: if entrapped within tissues, they can induce a local cellular recruitment with an inflammatory response contemporaneous to the resorption phase. In part, this problem is a consequence of poor solubility of the calcium alginates in water. Although calcium alginate fibers can exchange calcium ions with sodium ions from the wound exudate to create a calcium/sodium alginate fibers, the residual alginates are thought to be not totally degradable in vivo. Rapid and non- destructive characterization of series of the crude alginates and calcium alginate fibers has been performed using Raman spectroscopy with near IR excitation. Study of structural organization of the polymeric chains within calcium alginate fibers have been previously reported as made by confocal Raman multispectral imaging (CRMSI) in visible. Here, the Raman approach has been used to monitor the ion exchange reactions for different types of alginates and their salts in vitro. For in vivo evaluation, histological sections of alginate-treated rat tissue have been analyzed by light microscopy and CRMSI. The in vitro Raman modeling and the histochemical mapping were a necessary precursor for application of the Raman microprobe to follow in a non-invasive way the alginate-cell molecular interactions in rat tissue.

  12. Modelling molecular interaction pathways using a two-stage identification algorithm.

    PubMed

    Gormley, Padhraig; Li, Kang; Irwin, George W

    2007-08-01

    In systems biology, molecular interactions are typically modelled using white-box methods, usually based on mass action kinetics. Unfortunately, problems with dimensionality can arise when the number of molecular species in the system is very large, which makes the system modelling and behavior simulation extremely difficult or computationally too expensive. As an alternative, this paper investigates the identification of two molecular interaction pathways using a black-box approach. This type of method creates a simple linear-in-the-parameters model using regression of data, where the output of the model at any time is a function of previous system states of interest. One of the main objectives in building black-box models is to produce an optimal sparse nonlinear one to effectively represent the system behavior. In this paper, it is achieved by applying an efficient iterative approach, where the terms in the regression model are selected and refined using a forward and backward subset selection algorithm. The method is applied to model identification for the MAPK signal transduction pathway and the Brusselator using noisy data of different sizes. Simulation results confirm the efficacy of the black-box modelling method which offers an alternative to the computationally expensive conventional approach. PMID:19003449

  13. Molecular models of alginic acid: Interactions with calcium ions and calcite surfaces

    NASA Astrophysics Data System (ADS)

    Perry, Thomas D.; Cygan, Randall T.; Mitchell, Ralph

    2006-07-01

    Cation binding by polysaccharides is observed in many environments and is important for predictive environmental modeling, and numerous industrial and food technology applications. The complexities of these cation-organic interactions are well suited for predictive molecular modeling and the analysis of conformation and configuration of polysaccharides and their influence on cation binding. In this study, alginic acid was chosen as a model polymer system and representative disaccharide and polysaccharide subunits were developed. Molecular dynamics simulation of the torsion angles of the ether linkage between various monomeric subunits identified local and global energy minima for selected disaccharides. The simulations indicate stable disaccharide configurations and a common global energy minimum for all disaccharide models at Φ = 274 ± 7°, Ψ = 227 ± 5°, where Φ and Ψ are the torsion angles about the ether linkage. The ability of disaccharide subunits to bind calcium ions and to associate with the (101¯4) surface of calcite was also investigated. Molecular models of disaccharide interactions with calcite provide binding energy differences for conformations that are related to the proximity and residence densities of the electron-donating moieties with calcium ions on the calcite surface, which are controlled, in part, by the torsion of the ether linkage between monosaccharide units. Dynamically optimized configurations for polymer alginate models with calcium ions were also derived.

  14. Molecular modeling of polymer composite-analyte interactions in electronic nose sensors

    NASA Technical Reports Server (NTRS)

    Shevade, A. V.; Ryan, M. A.; Homer, M. L.; Manfreda, A. M.; Zhou, H.; Manatt, K. S.

    2003-01-01

    We report a molecular modeling study to investigate the polymer-carbon black (CB) composite-analyte interactions in resistive sensors. These sensors comprise the JPL electronic nose (ENose) sensing array developed for monitoring breathing air in human habitats. The polymer in the composite is modeled based on its stereoisomerism and sequence isomerism, while the CB is modeled as uncharged naphthalene rings with no hydrogens. The Dreiding 2.21 force field is used for the polymer, solvent molecules and graphite parameters are assigned to the carbon black atoms. A combination of molecular mechanics (MM) and molecular dynamics (NPT-MD and NVT-MD) techniques are used to obtain the equilibrium composite structure by inserting naphthalene rings in the polymer matrix. Polymers considered for this work include poly(4-vinylphenol), polyethylene oxide, and ethyl cellulose. Analytes studied are representative of both inorganic and organic compounds. The results are analyzed for the composite microstructure by calculating the radial distribution profiles as well as for the sensor response by predicting the interaction energies of the analytes with the composites. c2003 Elsevier Science B.V. All rights reserved.

  15. Modelling molecular interaction pathways using a two-stage identification algorithm

    PubMed Central

    Li, Kang; Irwin, George W.

    2008-01-01

    In systems biology, molecular interactions are typically modelled using white-box methods, usually based on mass action kinetics. Unfortunately, problems with dimensionality can arise when the number of molecular species in the system is very large, which makes the system modelling and behavior simulation extremely difficult or computationally too expensive. As an alternative, this paper investigates the identification of two molecular interaction pathways using a black-box approach. This type of method creates a simple linear-in-the-parameters model using regression of data, where the output of the model at any time is a function of previous system states of interest. One of the main objectives in building black-box models is to produce an optimal sparse nonlinear one to effectively represent the system behavior. In this paper, it is achieved by applying an efficient iterative approach, where the terms in the regression model are selected and refined using a forward and backward subset selection algorithm. The method is applied to model identification for the MAPK signal transduction pathway and the Brusselator using noisy data of different sizes. Simulation results confirm the efficacy of the black-box modelling method which offers an alternative to the computationally expensive conventional approach. PMID:19003449

  16. Investigation of possible interaction between pinaverium bromide and digoxin.

    PubMed

    Weitzel, O; Seidel, G; Engelbert, S; Berksoy, M; Eberhardt, G; Bode, R

    1983-01-01

    A single-blind study was carried out in 25 patients, who were receiving maintenance therapy for congestive heart failure with digoxin, to investigate the effect on steady-state plasma digoxin levels of concomitant administration of the spasmolytic, pinaverium bromide (50 mg 3-times daily). Patients received pinaverium bromide for 12 days followed by placebo for a further 7 days. Assessment of the results in 21 patients showed no evidence of any statistically significant variations in plasma digoxin levels during either treatment period or in the clinical observations which might indicate drug interaction. PMID:6653138

  17. Coarse-Grained Molecular Dynamics Simulations of Membrane-Trehalose Interactions.

    PubMed

    Kapla, Jon; Stevensson, Baltzar; Maliniak, Arnold

    2016-09-15

    It is well established that trehalose (TRH) affects the physical properties of lipid bilayers and stabilizes biological membranes. We present molecular dynamics (MD) computer simulations to investigate the interactions between lipid membranes formed by 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and TRH. Both atomistic and coarse-grained (CG) interaction models were employed, and the coarse graining of DMPC leads to a reduction in the acyl chain length corresponding to a 1,2-dilauroyl-sn-glycero-3-phosphocholine lipid (DLPC). Several modifications of the Martini interaction model, used for CG simulations, were implemented, resulting in different potentials of mean force (PMFs) for DMPC bilayer-TRH interactions. These PMFs were subsequently used in a simple two-site analytical model for the description of sugar binding at the membrane interface. In contrast to that in atomistic MD simulations, the binding in the CG model was not in agreement with the two-site model. Our interpretation is that the interaction balance, involving water, TRH, and lipids, in the CG systems needs further tuning of the force-field parameters. The area per lipid is only weakly affected by TRH concentration, whereas the compressibility modulus related to the fluctuations of the membrane increases with an increase in TRH content. In agreement with experimental findings, the bending modulus is not affected by the inclusion of TRH. The important aspects of lipid bilayer interactions with biomolecules are membrane curvature generation and sensing. In the present investigation, membrane curvature is generated by artificial buckling of the bilayer in one dimension. It turns out that TRH prefers the regions with the highest curvature, which enables the most favorable situation for lipid-sugar interactions. PMID:27530142

  18. Investigations and advanced concepts on gyrotron interaction modeling and simulations

    NASA Astrophysics Data System (ADS)

    Avramidis, K. A.

    2015-12-01

    In gyrotron theory, the interaction between the electron beam and the high frequency electromagnetic field is commonly modeled using the slow variables approach. The slow variables are quantities that vary slowly in time in comparison to the electron cyclotron frequency. They represent the electron momentum and the high frequency field of the resonant TE modes in the gyrotron cavity. For their definition, some reference frequencies need to be introduced. These include the so-called averaging frequency, used to define the slow variable corresponding to the electron momentum, and the carrier frequencies, used to define the slow variables corresponding to the field envelopes of the modes. From the mathematical point of view, the choice of the reference frequencies is, to some extent, arbitrary. However, from the numerical point of view, there are arguments that point toward specific choices, in the sense that these choices are advantageous in terms of simulation speed and accuracy. In this paper, the typical monochromatic gyrotron operation is considered, and the numerical integration of the interaction equations is performed by the trajectory approach, since it is the fastest, and therefore it is the one that is most commonly used. The influence of the choice of the reference frequencies on the interaction simulations is studied using theoretical arguments, as well as numerical simulations. From these investigations, appropriate choices for the values of the reference frequencies are identified. In addition, novel, advanced concepts for the definitions of these frequencies are addressed, and their benefits are demonstrated numerically.

  19. Investigations and advanced concepts on gyrotron interaction modeling and simulations

    SciTech Connect

    Avramidis, K. A.

    2015-12-15

    In gyrotron theory, the interaction between the electron beam and the high frequency electromagnetic field is commonly modeled using the slow variables approach. The slow variables are quantities that vary slowly in time in comparison to the electron cyclotron frequency. They represent the electron momentum and the high frequency field of the resonant TE modes in the gyrotron cavity. For their definition, some reference frequencies need to be introduced. These include the so-called averaging frequency, used to define the slow variable corresponding to the electron momentum, and the carrier frequencies, used to define the slow variables corresponding to the field envelopes of the modes. From the mathematical point of view, the choice of the reference frequencies is, to some extent, arbitrary. However, from the numerical point of view, there are arguments that point toward specific choices, in the sense that these choices are advantageous in terms of simulation speed and accuracy. In this paper, the typical monochromatic gyrotron operation is considered, and the numerical integration of the interaction equations is performed by the trajectory approach, since it is the fastest, and therefore it is the one that is most commonly used. The influence of the choice of the reference frequencies on the interaction simulations is studied using theoretical arguments, as well as numerical simulations. From these investigations, appropriate choices for the values of the reference frequencies are identified. In addition, novel, advanced concepts for the definitions of these frequencies are addressed, and their benefits are demonstrated numerically.

  20. Investigation of cellular responses upon interaction with silver nanoparticles

    PubMed Central

    Subbiah, Ramesh; Jeon, Seong Beom; Park, Kwideok; Ahn, Sang Jung; Yun, Kyusik

    2015-01-01

    In order for nanoparticles (NPs) to be applied in the biomedical field, a thorough investigation of their interactions with biological systems is required. Although this is a growing area of research, there is a paucity of comprehensive data in cell-based studies. To address this, we analyzed the physicomechanical responses of human alveolar epithelial cells (A549), mouse fibroblasts (NIH3T3), and human bone marrow stromal cells (HS-5), following their interaction with silver nanoparticles (AgNPs). When compared with kanamycin, AgNPs exhibited moderate antibacterial activity. Cell viability ranged from ≤80% at a high AgNPs dose (40 µg/mL) to >95% at a low dose (10 µg/mL). We also used atomic force microscopy-coupled force spectroscopy to evaluate the biophysical and biomechanical properties of cells. This revealed that AgNPs treatment increased the surface roughness (P<0.001) and stiffness (P<0.001) of cells. Certain cellular changes are likely due to interaction of the AgNPs with the cell surface. The degree to which cellular morphology was altered directly proportional to the level of AgNP-induced cytotoxicity. Together, these data suggest that atomic force microscopy can be used as a potential tool to develop a biomechanics-based biomarker for the evaluation of NP-dependent cytotoxicity and cytopathology. PMID:26346562

  1. Investigation of cellular responses upon interaction with silver nanoparticles.

    PubMed

    Subbiah, Ramesh; Jeon, Seong Beom; Park, Kwideok; Ahn, Sang Jung; Yun, Kyusik

    2015-01-01

    In order for nanoparticles (NPs) to be applied in the biomedical field, a thorough investigation of their interactions with biological systems is required. Although this is a growing area of research, there is a paucity of comprehensive data in cell-based studies. To address this, we analyzed the physicomechanical responses of human alveolar epithelial cells (A549), mouse fibroblasts (NIH3T3), and human bone marrow stromal cells (HS-5), following their interaction with silver nanoparticles (AgNPs). When compared with kanamycin, AgNPs exhibited moderate antibacterial activity. Cell viability ranged from ≤ 80% at a high AgNPs dose (40 µg/mL) to >95% at a low dose (10 µg/mL). We also used atomic force microscopy-coupled force spectroscopy to evaluate the biophysical and biomechanical properties of cells. This revealed that AgNPs treatment increased the surface roughness (P<0.001) and stiffness (P<0.001) of cells. Certain cellular changes are likely due to interaction of the AgNPs with the cell surface. The degree to which cellular morphology was altered directly proportional to the level of AgNP-induced cytotoxicity. Together, these data suggest that atomic force microscopy can be used as a potential tool to develop a biomechanics-based biomarker for the evaluation of NP-dependent cytotoxicity and cytopathology. PMID:26346562

  2. A molecular investigation of adsorption onto mineral pigments

    NASA Astrophysics Data System (ADS)

    Ninness, Brian J.

    Pigment suspensions are important in several processes such as ceramics, paints, inks, and coatings. In the wet state, pigments are combined with a variety of chemical species such as polymers, surfactants, and polyelectrolytes which produce a complex colloidal system. The adsorption, desorption, and redistribution of these species at the pigment-aqueous solution interface can have an impact on the behavior in both the wet state or its final dried state. The goal of this work is to establish a molecular picture of the adsorption properties of these pigmented systems. A novel in situ infrared technique has been developed which allows the detection of adsorbed surface species on pigment particles in an aqueous environment. The technique involves the use of a polymeric binder to anchor the colloidal pigment particles to the surface of an internal reflection element (IRE). The binder only weakly perturbs about 25% of the reactive surface sites (hydroxyl groups) on silica. The reaction of succinic anhydride with an aminosilanized silica surface has been quantified using this technique. The adsorption dynamics of the cationic surfactant cetyltrimethylammonium bromide (C16TAB) at the TiO2-aqueous solution interface has been investigated using Fourier transform infrared-attenuated total reflection spectroscopy (FTIR-ATR) and electrokinetic analysis. At low bulk concentrations, C16TAB is shown to adsorb as isolated islands with a "defective" bilayer structure. Anionic probe molecules are shown to effectively "tune" the adsorbed surfactant microstructure. The results indicate that the structure of the adsorbed surfactant layer, and not the amount of adsorbed surfactant, dictates the subsequent adsorption behavior of the system. Atomic Layer Deposition is used to deposit a TiO2 layer onto the surfaces of silica and kaolin pigments. The process involves the cyclic reaction sequence of the vapors of TiCl4 and H2O. Three complete deposition cycles are needed before the surfaces

  3. Amino acids as co-amorphous stabilizers for poorly water-soluble drugs--Part 2: molecular interactions.

    PubMed

    Löbmann, Korbinian; Laitinen, Riikka; Strachan, Clare; Rades, Thomas; Grohganz, Holger

    2013-11-01

    The formation of co-amorphous drug-drug mixtures has proved to be a powerful approach to stabilize the amorphous form and at the same time increase the dissolution of poorly water-soluble drugs. Molecular interactions in these co-amorphous formulations can play a crucial role in stabilization and dissolution enhancement. In this regard, Fourier-transform infrared spectroscopy (FTIR) is a valuable tool to analyze the molecular near range order of the compounds in the co-amorphous mixtures. In this study, several co-amorphous drugs--low molecular weight excipient blends--have been analyzed with FTIR spectroscopy. Molecular interactions of the drugs carbamazepine and indomethacin with the amino acids arginine, phenylalanine, and tryptophan were investigated. The amino acids were chosen from the biological target site of both drugs and prepared as co-amorphous formulations together with the drugs by vibrational ball milling. A detailed analysis of the FTIR spectra of these formulations revealed specific peak shifts in the vibrational modes of functional groups of drug and amino acid, as long as one amino acid from the biological target site was present in the blends. These peak shifts indicate that the drugs formed specific molecular interactions (hydrogen bonding and π-π interactions) with the amino acids. In the drug-amino acid mixtures that contained amino acids which were not present at the biological target site, no such interactions were identified. This study shows the potential of amino acids as small molecular weight excipients in co-amorphous formulations to stabilize the amorphous form of a poorly water-soluble drug through strong and specific molecular interactions with the drug.

  4. A survey for Galactic supernova remnant/molecular cloud interactions ssing carbon monoxide

    NASA Astrophysics Data System (ADS)

    Kilpatrick, Charles; Rieke, George; Bieging, John

    2016-06-01

    Supernova remnants are one of the primary engines through which stars add energy to the interstellar medium. The efficiency of this transfer of energy is enhanced where supernova remnants encounter dense interstellar gas, such as in molecular clouds. Unique signatures have been observed toward these supernova remnant/molecular cloud interactions in the form of unusual molecular line profiles and bright non-thermal radiation. The sites of these interactions also provide some of the best examples for evidence of cosmic-ray acceleration and Galactic sources of very high-energy gamma-rays. Despite the large number of individual studies that examine supernova remnant/molecular cloud interactions, very little is known about their overall rates and characteristics. This lack of information limits the usefulness of individual supernova remnant/molecular cloud interactions to enhance our understanding of supernova feedback and cosmic-ray acceleration. I will discuss recent work studying large populations of supernova remnants in the 12CO J = 2 ‑ 1 and J = 3 ‑ 2 lines and the observational signatures associated with molecular shocks from supernova ejecta. Broadened molecular lines and molecular line ratios indicative of warm gas can be used to identify and characterize populations of supernova remnant/molecular cloud interactions. From this large sample, I will discuss new constraints on the energetic processes to which supernova remnants contribute, especially the rate of GeV and TeV gamma-ray production associated with supernova remnant/molecular cloud interfaces.

  5. Theoretical investigation of interaction between the set of ligands and α7 nicotinic acetylcholine receptor

    NASA Astrophysics Data System (ADS)

    Glukhova, O. E.; Prytkova, T. R.; Shmygin, D. S.

    2016-03-01

    Nicotinic acetylcholine receptors (nAChRs) are neuron receptor proteins that provide a transmission of nerve impulse through the synapses. They are composed of a pentametric assembly of five homologous subunits (5 α7 subunits for α7nAChR, for example), oriented around the central pore. These receptors might be found in the chemical synapses of central and peripheral nervous system, and also in the neuromuscular synapses. Transmembrane domain of the one of such receptors constitutes ion channel. The conductive properties of ion channel strongly depend on the receptor conformation changes in the response of binding with some molecule, f.e. acetylcholine. Investigation of interaction between ligands and acetylcholine receptor is important for drug design. In this work we investigate theoretically the interaction between the set of different ligands (such as vanillin, thymoquinone, etc.) and the nicotinic acetylcholine receptor (primarily with subunit of the α7nAChR) by different methods and packages (AutodockVina, GROMACS, KVAZAR, HARLEM, VMD). We calculate interaction energy between different ligands in the subunit using molecular dynamics. On the base of obtained calculation results and using molecular docking we found an optimal location of different ligands in the subunit.

  6. Advanced Characterization of Molecular Interactions in TALSPEAK-like Separations Systems

    SciTech Connect

    Nash, Kenneth; Guelis, Artem; Lumetta, Gregg J.; Sinkov, Sergey

    2015-10-21

    Combining unit operations in advanced aqueous reprocessing schemes brings obvious process compactness advantages, but at the same time greater complexity in process design and operation. Unraveling these interactions requires increasingly sophisticated analytical tools and unique approaches for adequate analysis and characterization that probe molecular scale interactions. Conventional slope analysis methods of solvent extraction are too indirect to provide much insight into such interactions. This project proposed the development and verification of several analytical tools based on studies of TALSPEAK-like aqueous processes. As such, the chemistry of trivalent fission product lanthanides, americium, curium, plutonium, neptunium and uranium figure prominently in these studies. As the project was executed, the primary focus fell upon the chemistry or trivalent lanthanides and actinides. The intent of the investigation was to compare and contrast the results from these various complementary techniques/studies to provide a stronger basis for predicting the performance of extractant/diluent mixtures as media for metal ion separations. As many/most of these techniques require the presence of metal ions at elevated concentrations, it was expected that these studies would take this investigation into the realm of patterns of supramolecular organization of metal complexes and extractants in concentrated aqueous/organic media. We expected to advance knowledge of the processes that enable and limit solvent extraction reactions as a result of the application of fundamental chemical principles to explaining interactions in complex media.

  7. Toward a Molecular Understanding of the Mechanism of Cryopreservation by Polyampholytes: Cell Membrane Interactions and Hydrophobicity.

    PubMed

    Rajan, Robin; Hayashi, Fumiaki; Nagashima, Toshio; Matsumura, Kazuaki

    2016-05-01

    Cryopreservation enables long-term preservation of cells at ultralow temperatures. Current cryoprotective agents (CPAs) have several limitations, making it imperative to develop CPAs with advanced properties. Previously, we developed a novel synthetic polyampholyte-based CPA, copolymer of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and methacrylic acid(MAA) (poly(MAA-DMAEMA)), which showed excellent efficiency and biocompatibility. Introduction of hydrophobicity increased its efficiency significantly. Herein, we investigated the activity of other polyampholytes. We prepared two zwitterionic polymers, poly(sulfobetaine) (SPB) and poly(carboxymethyl betaine) (CMB), and compared their efficiency with poly(MAA-DMAEMA). Poly-SPB showed only intermediate property and poly-CMB showed no cryoprotective property. These data suggested that the polymer structure strongly influences cryoprotection, providing an impetus to elucidate the molecular mechanism of cryopreservation. We investigated the mechanism by studying the interaction of polymers with cell membrane, which allowed us to identify the interactions responsible for imparting different properties. Results unambiguously demonstrated that polyampholytes cryopreserve cells by strongly interacting with cell membrane, with hydrophobicity increasing the affinity for membrane interaction, which enables it to protect the membrane from various freezing-induced damages. Additionally, cryoprotective polymers, especially their hydrophobic derivatives, inhibit the recrystallization of ice, thus averting cell death. Hence, our results provide an important insight into the complex mechanism of cryopreservation, which might facilitate the rational design of polymeric CPAs with improved efficiency. PMID:27077533

  8. Study on the interaction of catalase with pesticides by flow injection chemiluminescence and molecular docking.

    PubMed

    Tan, Xijuan; Wang, Zhuming; Chen, Donghua; Luo, Kai; Xiong, Xunyu; Song, Zhenghua

    2014-08-01

    The interaction mechanisms of catalase (CAT) with pesticides (including organophosphates: disulfoton, isofenphos-methyl, malathion, isocarbophos, dimethoate, dipterex, methamidophos and acephate; carbamates: carbaryl and methomyl; pyrethroids: fenvalerate and deltamethrin) were first investigated by flow injection (FI) chemiluminescence (CL) analysis and molecular docking. By homemade FI-CL model of lg[(I0-I)/I]=lgK+nlg[D], it was found that the binding processes of pesticides to CAT were spontaneous with the apparent binding constants K of 10(3)-10(5) L mol(-1) and the numbers of binding sites about 1.0. The binding abilities of pesticides to CAT followed the order: fenvalerate>deltamethrin>disulfoton>isofenphos-methyl>carbaryl>malathion>isocarbophos>dimethoate>dipterex>acephate>methomyl>methamidophos, which was generally similar to the order of determination sensitivity of pesticides. The thermodynamic parameters revealed that CAT bound with hydrophobic pesticides by hydrophobic interaction force, and with hydrophilic pesticides by hydrogen bond and van der Waals force. The pesticides to CAT molecular docking study showed that pesticides could enter into the cavity locating among the four subdomains of CAT, giving the specific amino acid residues and hydrogen bonds involved in CAT-pesticides interaction. It was also found that the lgK values of pesticides to CAT increased regularly with increasing lgP, Mr, MR and MV, suggesting that the hydrophobicity and steric property of pesticide played essential roles in its binding to CAT.

  9. Molecular dynamics simulation for interlayer interactions of graphene nanoribbons with multiple layers

    NASA Astrophysics Data System (ADS)

    Nazemnezhad, Reza; Zare, Mojtaba; Hosseini-Hashemi, Shahrokh; Shokrollahi, Hassan

    2016-10-01

    A new study is conducted with the aid of molecular dynamics (MD) simulation to investigate the effect of shear modulus value of the interlayer van der Waals (vdWs) interactions on free vibration of cantilever multi-layer graphene nanoribbons (MLGNRs). The corresponding calibrated nonlocal parameters of the nonlocal model are obtained accordingly. The vdWs interactions are treated as the cores between every two adjacent graphene layers and their equivalent shear modulus is calculated using MD simulation. The obtained resonant frequencies via the nonlocal sandwich model are compared to the MD simulation results to calibrate the nonlocal parameter. Results reveal a strong conclusion that the calibrated nonlocal parameter is dependent on the values of interlayer shear modulus.

  10. Isolate extended state in the DNA molecular transistor with surface interaction

    NASA Astrophysics Data System (ADS)

    Wang, Le; Qin, Zhi-Jie

    2016-02-01

    The field effect characteristic of a DNA molecular device is investigated in a tight binding model with binary disorder and side site correlation. Using the transfer-matrix method and Landauer-Büttiker theory, we find that the system has isolated extended state that is irrespective of the DNA sequence and can be modulated by the gate voltage. When the gate voltage reaches some proper value, the isolated extended state appears at the Fermi level of the system and the long range charge transport is greatly enhanced. We attribute this phenomenon to the combination of the external field, the surface interaction, and the intrinsic disorder of DNA. The result is a generic feature of the nanowire with binary disorder and surface interaction.

  11. Demixing transition and molecular interactions in Poly(N-isopropyl acrylamide) solutions compared to its monomer

    NASA Astrophysics Data System (ADS)

    Futscher, Moritz; Philipp, Martine; Mueller-Buschbaum, Peter; Schulte, Alfons

    2015-03-01

    Temperature-sensitive hydrogels such as poly(N-isopropyl acrylamide) (PNIPAM) exhibit a coil to globule transition of the polymer chains with a lower critical solution temperature (LCST) near 305 K. The cooperative dehydration of bound water molecules upon heating plays a significant role. The hydrogen bonding with the the amide groups in the side chains has to be contrasted with the hydration interaction of the hydrophobic main chain hydro-carbons. Employing FTIR spectroscopy we probe molecular changes in the various chemical groups. PNIPAM and its monomer NIPAM are investigated at a concentration of 20% in aqueous solution. We observe a nearly discontinuous shift of the the peak frequencies and the intensities of vibrational bands (amides, CH) in PNIPAM, whereas in NIPAM there is a continuous linear shift with temperature. The results are discussed with respect to hydration changes in the amide group and cooperative interactions with bound water along the backbone chain.

  12. Molecular dynamics simulations of interfacial interactions between small nanoparticles during diffusion-limited aggregation

    NASA Astrophysics Data System (ADS)

    Lu, Jing; Liu, Dongmei; Yang, Xiaonan; Zhao, Ying; Liu, Haixing; Tang, Huan; Cui, Fuyi

    2015-12-01

    Due to the limitations of experimental methods at the atomic level, research on the aggregation of small nanoparticles (D < 5 nm) in aqueous solutions is quite rare. The aggregation of small nanoparticles in aqueous solutions is very different than that of normal sized nanoparticles. The interfacial interactions play a dominant role in the aggregation of small nanoparticles. In this paper, molecular dynamics simulations, which can explore the microscopic behavior of nanoparticles during the diffusion-limited aggregation at an atomic level, were employed to reveal the aggregation mechanism of small nanoparticles in aqueous solutions. First, the aggregation processes and aggregate structure were depicted. Second, the particle-particle interaction and surface diffusion of nanoparticles during aggregation were investigated. Third, the water-mediated interactions during aggregation were ascertained. The results indicate that the aggregation of nanoparticle in aqueous solutions is affected by particle size. The strong particle-particle interaction and high surface diffusion result in the formation of particle-particle bonds of 2 nm TiO2 nanoparticles, and the water-mediated interaction plays an important role in the aggregation process of 3 and 4 nm TiO2 nanoparticles.

  13. "Zwitterionic Proton Sponge" Hydrogen Bonding Investigations on the Basis of Car-Parrinello Molecular Dynamics.

    PubMed

    Jezierska, Aneta; Panek, Jarosław J

    2015-06-22

    1,8-Bis(dimethylamino)-4,5-dihydroxynaphthalene has been investigated on the basis of static DFT computations and Car-Parrinello molecular dynamics. The simulations were performed in the gas phase and in the solid state. The studied "zwitterionic proton sponge" possesses two, short intramolecular hydrogen bonds (O-H···O and N-H···N) classified as Low Barrier Hydrogen Bonds (LBHBs); therefore, the system studied is strongly anharmonic. In addition, the compound exists as a "zwitterion" in solution and in the solid state, thus the intramolecular hydrogen bonds belong to the class of charge-assisted interactions. The applied quantum-chemical methods enabled investigations of metric and spectroscopic parameters of the molecule. The time-evolution investigations of the H-bonding showed a strong delocalization of the bridge protons and their high mobility, reflected in the low barriers on the free energy surfaces. Frequent proton transfer phenomena were noticed. The power spectra of atomic velocity were computed to analyze the vibrational features associated with O-H and N-H stretching. A broad absorption was indicated for both hydrogen bridges. For the first time, Car-Parrinello molecular dynamics results are reported for the compound, and they indicate a broad, shallow but not barrierless, potential well for each of the bridge protons. PMID:25965324

  14. Interaction of cyproheptadine hydrochloride with human serum albumin using spectroscopy and molecular modeling methods.

    PubMed

    Jiang, Hua; Chen, Rongrong; Wang, Hongcui; Pu, Hanlin

    2013-01-01

    The interaction between cyproheptadine hydrochloride (CYP) and human serum albumin (HSA) was investigated by fluorescence spectroscopy, UV-vis absorption spectroscopy, Fourier transform infrared spectroscopy (FT-IR) and molecular modeling at a physiological pH (7.40). Fluorescence of HSA was quenched remarkably by CYP and the quenching mechanism was considered as static quenching since it formed a complex. The association constants Ka and number of binding sites n were calculated at different temperatures. According to Förster's theory of non-radiation energy transfer, the distance r between donor (human serum albumin) and acceptor (cyproheptadine hydrochloride) was obtained. The effect of common ions on the binding constant was also investigated. The effect of CYP on the conformation of HSA was analyzed using FT-IR, synchronous fluorescence spectroscopy and 3D fluorescence spectra. The thermodynamic parameters ΔH and ΔS were calculated to be -14.37 kJ mol(-1) and 38.03 J mol(-1) K(-1), respectively, which suggested that hydrophobic forces played a major role in stabilizing the HSA-CYP complex. In addition, examination of molecular modeling indicated that CYP could bind to site I of HSA and that hydrophobic interaction was the major acting force, which was in agreement with binding mode studies.

  15. Investigate the Binding of Catechins to Trypsin Using Docking and Molecular Dynamics Simulation

    PubMed Central

    Cui, Fengchao; Yang, Kecheng; Li, Yunqi

    2015-01-01

    To explore the inhibitory mechanism of catechins for digestive enzymes, we investigated the binding mode of catechins to a typical digestive enzyme-trypsin and analyzed the structure-activity relationship of catechins, using an integration of molecular docking, molecular dynamics simulation and binding free energy calculation. We found that catechins with different structures bound to a conservative pocket S1 of trypsin, which is comprised of residues 189–195, 214–220 and 225–228. In the trypsin-catechin complexes, Asp189 by forming strong hydrogen bonding, and Gln192, Trp215 and Gly216 through hydrophobic interactions, all significantly contribute to the binding of catechins. The number and the position of hydroxyl and aromatic groups, the structure of stereoisomers, and the orientation of catechins in the binding pocket S1 of trypsin all affect the binding affinity. The binding affinity is in the order of Epigallocatechin gallate (EGCG) > Epicatechin gallate (ECG) > Epicatechin (EC) > Epigallocatechin (EGC), and 2R-3R EGCG shows the strongest binding affinity out of other stereoisomers. Meanwhile, the synergic conformational changes of residues and catechins were also analyzed. These findings will be helpful in understanding the knowledge of interactions between catechins and trypsin and referable for the design of novel polyphenol based functional food and nutriceutical formulas. PMID:25938485

  16. Structural analysis and investigation of molecular properties of Cefpodoxime acid, a third generation antibiotic

    NASA Astrophysics Data System (ADS)

    Suganthi, S.; Balu, P.; Sathyanarayanamoorthi, V.; Kannappan, V.; Kamil, M. G. Mohamed; Kumar, R.

    2016-03-01

    Extensive quantum mechanical studies are carried out on Cefpodoxime acid (CA), a new generation drug by Hartree-Fock (HF) and B3LYP methods to understand the structural and spectral characteristics of the molecule. The most stable geometry of the molecule was optimized and the bond parameters were reported. The spectroscopic properties of this pharmaceutically important compound were investigated by FT-IR, FT-Raman, UV and 1H NMR techniques. The scaled vibrational frequencies of CA in the ground state are calculated by HF and B3LYP methods with 6-311++G (d, p) basis set and compared with the observed FT-IR and FT-Raman spectra. The vibrational spectral analysis indicates the presence of two intra molecular hydrogen bonds in the molecule which is supported by theoretical study. 1H NMR chemical shifts (δ) were calculated for the CA molecule and compared with the experimental values. The theoretical electronic absorption spectral data in water and ethanol solvents were computed by TD-DFT method. UV-Vis absorption spectra of CA are recorded in these two solvents and compared with theoretical spectra. The spectral data and natural bond orbital (NBO) analysis confirm the occurrence of intra molecular interactions in CA. The electronic distribution, in conjunction with electrophilicity index of CA was used to establish the active site and type of interaction between CA and beta lactamases. Mulliken population analysis on atomic charges is also carried out and thermodynamic properties of the title compound are calculated.

  17. Investigate the binding of catechins to trypsin using docking and molecular dynamics simulation.

    PubMed

    Cui, Fengchao; Yang, Kecheng; Li, Yunqi

    2015-01-01

    To explore the inhibitory mechanism of catechins for digestive enzymes, we investigated the binding mode of catechins to a typical digestive enzyme-trypsin and analyzed the structure-activity relationship of catechins, using an integration of molecular docking, molecular dynamics simulation and binding free energy calculation. We found that catechins with different structures bound to a conservative pocket S1 of trypsin, which is comprised of residues 189-195, 214-220 and 225-228. In the trypsin-catechin complexes, Asp189 by forming strong hydrogen bonding, and Gln192, Trp215 and Gly216 through hydrophobic interactions, all significantly contribute to the binding of catechins. The number and the position of hydroxyl and aromatic groups, the structure of stereoisomers, and the orientation of catechins in the binding pocket S1 of trypsin all affect the binding affinity. The binding affinity is in the order of Epigallocatechin gallate (EGCG) > Epicatechin gallate (ECG) > Epicatechin (EC) > Epigallocatechin (EGC), and 2R-3R EGCG shows the strongest binding affinity out of other stereoisomers. Meanwhile, the synergic conformational changes of residues and catechins were also analyzed. These findings will be helpful in understanding the knowledge of interactions between catechins and trypsin and referable for the design of novel polyphenol based functional food and nutriceutical formulas. PMID:25938485

  18. [Molecular genetic investigation of sugar beet (Beta vulgaris L.)].

    PubMed

    Butorina, A K; Kornienko, A V

    2011-10-01

    Molecular genetic studies of sugar beet (Beta vulgaris L.) are reviewed as a basis for the development of genomics of this species. The methods used to study structural and functional genomics are considered. The results and their application to increase the efficiency of sugar beet breeding are discussed.

  19. Investigation of the torsional barrier of EDOT using molecular mechanics and DFT methods.

    PubMed

    Durães, Jussara A; da Silva Filho, Demétrio A; Ceschin, Artemis M; Sales, Maria J A; Martins, João B L

    2014-08-01

    When heterocyclic monomers are polymerized by electrochemical or chemical methods, they form fully conjugated polymers which have a wide range of applications due to their outstanding electronic properties. Among this class of compounds, thiophene derivatives are widely used due to their chemical stability and synthesis flexibility. With the goal to investigate the torsion barrier of polymer chains, a few units of 3,4-ethylenedioxythiophene (EDOT) were chosen and submitted to molecular mechanics (MM), density functional theory (DFT) and coupled cluster CCSD(T) calculations. This study helps to understand the performance and transferability of force fields used in molecular mechanics and molecular dynamics simulations often used to describe structure-property relationships of those systems. Determination of inter-ring torsion angle was performed in a comparative study using both force field, DFT and CCSD(T) methods. A good agreement was noticed between MM and QC results and highlights the importance of the description of the interactions involving the oxygen atoms present in the structure of EDOT. These observations are related to the α,α-coupling that occurs between the monomer units and yields a linear polymer. DFT HOMO and LUMO orbitals were also presented. Finally, UV-vis spectra of EDOT units were obtained using several levels of theory by means of time-dependent DFT calculations (TD-DFT). PMID:25116151

  20. Investigation of protein-fatty acid interactions in zein films

    NASA Astrophysics Data System (ADS)

    Wang, Qin

    Zein, the prolamin of corn, has shown potential as industrial biopolymer for packaging and agricultural uses. Previous researchers plasticized zein with oleic acid and extruded it into sheets and films. Such products showed reasonable tensile and water barrier properties. However, those properties were affected by film structure, which is believed controlled by the interaction between zein and plasticizer. The nature of those interactions is still not well understood. Protein-fatty acid interactions in zein resin films were investigated by surface plasmon resonance and atomic force microscopy in this work. Preliminary research was conducted to establish the effect of solvent systems on the plasticization of zein by oleic acid. Although slight differences were observed, it was concluded that the use of 75% ethanol or 75% 2-propanol produced similar results. Surface plasmon resonance was employed to investigate zein static and dynamic adsorption on surfaces of hydrophilic and hydrophobic self-assembled monolayers (SAMs) generated by 11-mercaptoundecanoic acid or 1-octanethiol, respectively, and representing the two end groups of oleic acid. Results indicated that zein was adsorbed to both surfaces but showed higher affinity for hydrophilic groups. The corresponding thickness of zein specific binding layer on hydrophilic and hydrophobic SAMs was around 4.7 nm and 4.6 nm. Zein exhibited higher affinity for hydrophilic than for hydrophobic SAMs evidenced from the higher initial adsorption rate and ultimate surface coverage at all zein concentrations. Flushing surface with buffer would leave an apparent monolayer of zein, which is 5 times higher for hydrophilic than hydrophobic SAMs. This observation suggested that zein may use different sides of its molecule to interact with hydrophobic or hydrophilic groups. The surface topography of zein deposits on both SAMs was examined by atomic force microscopy. It was found that zein formed distinct ring-shaped structures with

  1. Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations.

    PubMed

    van Os, Jim; Rutten, Bart P; Myin-Germeys, Inez; Delespaul, Philippe; Viechtbauer, Wolfgang; van Zelst, Catherine; Bruggeman, Richard; Reininghaus, Ulrich; Morgan, Craig; Murray, Robin M; Di Forti, Marta; McGuire, Philip; Valmaggia, Lucia R; Kempton, Matthew J; Gayer-Anderson, Charlotte; Hubbard, Kathryn; Beards, Stephanie; Stilo, Simona A; Onyejiaka, Adanna; Bourque, Francois; Modinos, Gemma; Tognin, Stefania; Calem, Maria; O'Donovan, Michael C; Owen, Michael J; Holmans, Peter; Williams, Nigel; Craddock, Nicholas; Richards, Alexander; Humphreys, Isla; Meyer-Lindenberg, Andreas; Leweke, F Markus; Tost, Heike; Akdeniz, Ceren; Rohleder, Cathrin; Bumb, J Malte; Schwarz, Emanuel; Alptekin, Köksal; Üçok, Alp; Saka, Meram Can; Atbaşoğlu, E Cem; Gülöksüz, Sinan; Gumus-Akay, Guvem; Cihan, Burçin; Karadağ, Hasan; Soygür, Haldan; Cankurtaran, Eylem Şahin; Ulusoy, Semra; Akdede, Berna; Binbay, Tolga; Ayer, Ahmet; Noyan, Handan; Karadayı, Gülşah; Akturan, Elçin; Ulaş, Halis; Arango, Celso; Parellada, Mara; Bernardo, Miguel; Sanjuán, Julio; Bobes, Julio; Arrojo, Manuel; Santos, Jose Luis; Cuadrado, Pedro; Rodríguez Solano, José Juan; Carracedo, Angel; García Bernardo, Enrique; Roldán, Laura; López, Gonzalo; Cabrera, Bibiana; Cruz, Sabrina; Díaz Mesa, Eva Ma; Pouso, María; Jiménez, Estela; Sánchez, Teresa; Rapado, Marta; González, Emiliano; Martínez, Covadonga; Sánchez, Emilio; Olmeda, Ma Soledad; de Haan, Lieuwe; Velthorst, Eva; van der Gaag, Mark; Selten, Jean-Paul; van Dam, Daniella; van der Ven, Elsje; van der Meer, Floor; Messchaert, Elles; Kraan, Tamar; Burger, Nadine; Leboyer, Marion; Szoke, Andrei; Schürhoff, Franck; Llorca, Pierre-Michel; Jamain, Stéphane; Tortelli, Andrea; Frijda, Flora; Vilain, Jeanne; Galliot, Anne-Marie; Baudin, Grégoire; Ferchiou, Aziz; Richard, Jean-Romain; Bulzacka, Ewa; Charpeaud, Thomas; Tronche, Anne-Marie; De Hert, Marc; van Winkel, Ruud; Decoster, Jeroen; Derom, Catherine; Thiery, Evert; Stefanis, Nikos C; Sachs, Gabriele; Aschauer, Harald; Lasser, Iris; Winklbaur, Bernadette; Schlögelhofer, Monika; Riecher-Rössler, Anita; Borgwardt, Stefan; Walter, Anna; Harrisberger, Fabienne; Smieskova, Renata; Rapp, Charlotte; Ittig, Sarah; Soguel-dit-Piquard, Fabienne; Studerus, Erich; Klosterkötter, Joachim; Ruhrmann, Stephan; Paruch, Julia; Julkowski, Dominika; Hilboll, Desiree; Sham, Pak C; Cherny, Stacey S; Chen, Eric Y H; Campbell, Desmond D; Li, Miaoxin; Romeo-Casabona, Carlos María; Emaldi Cirión, Aitziber; Urruela Mora, Asier; Jones, Peter; Kirkbride, James; Cannon, Mary; Rujescu, Dan; Tarricone, Ilaria; Berardi, Domenico; Bonora, Elena; Seri, Marco; Marcacci, Thomas; Chiri, Luigi; Chierzi, Federico; Storbini, Viviana; Braca, Mauro; Minenna, Maria Gabriella; Donegani, Ivonne; Fioritti, Angelo; La Barbera, Daniele; La Cascia, Caterina Erika; Mulè, Alice; Sideli, Lucia; Sartorio, Rachele; Ferraro, Laura; Tripoli, Giada; Seminerio, Fabio; Marinaro, Anna Maria; McGorry, Patrick; Nelson, Barnaby; Amminger, G Paul; Pantelis, Christos; Menezes, Paulo R; Del-Ben, Cristina M; Gallo Tenan, Silvia H; Shuhama, Rosana; Ruggeri, Mirella; Tosato, Sarah; Lasalvia, Antonio; Bonetto, Chiara; Ira, Elisa; Nordentoft, Merete; Krebs, Marie-Odile; Barrantes-Vidal, Neus; Cristóbal, Paula; Kwapil, Thomas R; Brietzke, Elisa; Bressan, Rodrigo A; Gadelha, Ary; Maric, Nadja P; Andric, Sanja; Mihaljevic, Marina; Mirjanic, Tijana

    2014-07-01

    Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. PMID:24860087

  2. Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations

    PubMed Central

    2014-01-01

    Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi–center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. PMID:24860087

  3. Use of RNA polymerase molecular beacon assay to measure RNA polymerase interactions with model promoter fragments.

    PubMed

    Mekler, Vladimir; Severinov, Konstantin

    2015-01-01

    RNA polymerase-promoter interactions that keep the transcription initiation complex together are complex and multipartite, and formation of the RNA polymerase-promoter complex proceeds through multiple intermediates. Short promoter fragments can be used as a tool to dissect RNA polymerase-promoter interactions and to pinpoint elements responsible for specific properties of the entire promoter complex. A recently developed fluorometric molecular beacon assay allows one to monitor the enzyme interactions with various DNA probes and quantitatively characterize partial RNA polymerase-promoter interactions. Here, we present detailed protocols for the preparation of an Escherichia coli molecular beacon and its application to study RNA polymerase interactions with model promoter fragments.

  4. Experimental and molecular docking studies on DNA binding interaction of adefovir dipivoxil: Advances toward treatment of hepatitis B virus infections

    NASA Astrophysics Data System (ADS)

    Shahabadi, Nahid; Falsafi, Monireh

    The toxic interaction of adefovir dipivoxil with calf thymus DNA (CT-DNA) was investigated in vitro under simulated physiological conditions by multi-spectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated drug interacted with CT-DNA in a groove binding mode. The binding constant of UV-visible and the number of binding sites were 3.33 ± 0.2 × 104 L mol-1and 0.99, respectively. The fluorimetric studies showed that the reaction between the drug and CT-DNA is exothermic (ΔH = 34.4 kJ mol-1; ΔS = 184.32 J mol-1 K-1). Circular dichroism spectroscopy (CD) was employed to measure the conformational change of CT-DNA in the presence of adefovir dipivoxil, which verified the groove binding mode. Furthermore, the drug induces detectable changes in its viscosity. The molecular modeling results illustrated that adefovir strongly binds to groove of DNA by relative binding energy of docked structure -16.83 kJ mol-1. This combination of multiple spectroscopic techniques and molecular modeling methods can be widely used in the investigation on the toxic interaction of small molecular pollutants and drugs with bio macromolecules, which contributes to clarify the molecular mechanism of toxicity or side effect in vivo.

  5. Role of the Strength of Drug-Polymer Interactions on the Molecular Mobility and Crystallization Inhibition in Ketoconazole Solid Dispersions.

    PubMed

    Mistry, Pinal; Mohapatra, Sarat; Gopinath, Tata; Vogt, Frederick G; Suryanarayanan, Raj

    2015-09-01

    The effects of specific drug-polymer interactions (ionic or hydrogen-bonding) on the molecular mobility of model amorphous solid dispersions (ASDs) were investigated. ASDs of ketoconazole (KTZ), a weakly basic drug, with each of poly(acrylic acid) (PAA), poly(2-hydroxyethyl methacrylate) (PHEMA), and polyvinylpyrrolidone (PVP) were prepared. Drug-polymer interactions in the ASDs were evaluated by infrared and solid-state NMR, the molecular mobility quantified by dielectric spectroscopy, and crystallization onset monitored by differential scanning calorimetry (DSC) and variable temperature X-ray diffractometry (VTXRD). KTZ likely exhibited ionic interactions with PAA, hydrogen-bonding with PHEMA, and weaker dipole-dipole interactions with PVP. On the basis of dielectric spectroscopy, the α-relaxation times of the ASDs followed the order: PAA > PHEMA > PVP. In addition, the presence of ionic interactions also translated to a dramatic and disproportionate decrease in mobility as a function of polymer concentration. On the basis of both DSC and VTXRD, an increase in strength of interaction translated to higher crystallization onset temperature and a decrease in extent of crystallization. Stronger drug-polymer interactions, by reducing the molecular mobility, can potentially delay the crystallization onset temperature as well as crystallization extent.

  6. Molecular modeling of human BAD and its interaction with PKAc or PP1c.

    PubMed

    Yang, Jie

    2009-03-01

    To build up the structure of human BAD (Bcl-2 antagonist of cell death), subsequently combined with PKAc or PP1c (protein phosphatase 1), to investigate the interaction relationship between BAD and its kinase/PTPese at the molecular level. Additionally, it is concerned with the search for all optimal positions and orientations of a set of amino acid residues of BAD, while its binding sites include N-termini (Glu19, Ala27, and Ser34-Lys35), BH3-located helical domain (Arg98-Lys126), and C-termini (Trp154-Ser163 and Ser167-Gln168). The related sites of PKAc are mainly assembled in C-terminal alpha/beta-domain of PKAc, which comprises the KTL motif (47-49), Glu203 residue, a helical region (Asp241-Arg256), and the span from 328 to 333; while the interaction sites with BAD converge at C-terminal beta-domain of PP1c, which includes the DEK motif (166-168), the stretch from 179 to 197 including a helix (Glu184-Arg188), Glu230-Asp242 segment containing Val232-His237 helix, and Glu287-Leu289 loop. In conclusion, analysis of the complex between BAD and PKAc or PP1c provides a novel viewpoint on the structural origins of molecular recognition. And the complex models suggest that BH3 domain of BAD interact with PKAc or PP1c by electrostatic, van der Waals contacts, hydrogen bond and salt bridge. This is helpful for our development and research of some new drugs, especially mimetic BH3 peptides and inspires scientists with BAD complex and molecular mechanism of its integrating glycolysis and apoptosis.

  7. Investigation of Cellular Interactions of Nanoparticles by Helium Ion Microscopy

    SciTech Connect

    Arey, Bruce W.; Shutthanandan, V.; Xie, Yumei; Tolic, Ana; Williams, Nolann G.; Orr, Galya

    2011-06-01

    The helium ion mircroscope (HIM) probes light elements (e.g. C, N, O, P) with high contrast due to the large variation in secondary electron yield, which minimizes the necessity of specimen staining. A defining characteristic of HIM is its remarkable capability to neutralize charge by the implementation of an electron flood gun, which eliminates the need for coating non-conductive specimens for imaging at high resolution. In addition, the small convergence angle in HeIM offers a large depth of field (~5x FE-SEM), enabling tall structures to be viewed in focus within a single image. Taking advantage of these capabilities, we investigate the interactions of engineered nanoparticles (NPs) at the surface of alveolar type II epithelial cells grown at the air-liquid interface (ALI). The increasing use of nanomaterials in a wide range of commercial applications has the potential to increase human exposure to these materials, but the impact of such exposure on human health is still unclear. One of the main routs of exposure is the respiratory tract, where alveolar epithelial cells present a vulnerable target at the interface with ambient air. Since the cellular interactions of NPs govern the cellular response and ultimately determine the impact on human health, our studies will help delineating relationships between particle properties and cellular interactions and response to better evaluate NP toxicity or biocompatibility. The Rutherford backscattered ion (RBI) is a helium ions imaging mode, which backscatters helium ions from every element except hydrogen, with a backscatter yield that depends on the atomic number of the target. Energy-sensitive backscatter analysis is being developed, which when combined with RBI image information, supports elemental identification at helium ion nanometer resolution. This capability will enable distinguishing NPs from cell surface structures with nanometer resolution.

  8. Investigation of cellular interactions of nanoparticles by helium ion microscopy

    NASA Astrophysics Data System (ADS)

    Arey, B. W.; Shutthanandan, V.; Xie, Y.; Tolic, A.; Williams, N.; Orr, G.

    2011-06-01

    The helium ion microscope (HIM) probes light elements (e.g. C, N, O, P) with high contrast due to the large variation in secondary electron yield, which minimizes the necessity of specimen staining. A defining characteristic of HIM is its remarkable capability to neutralize charge by the implementation of an electron flood gun, which eliminates the need for coating non-conductive specimens for imaging at high resolution. In addition, the small convergence angle in HeIM offers a large depth of field (~5× FE-SEM), enabling tall structures to be viewed in focus within a single image. Taking advantage of these capabilities, we investigate the interactions of engineered nanoparticles (NPs) at the surface of alveolar type II epithelial cells grown at the airliquid interface (ALI). The increasing use of nanomaterials in a wide range of commercial applications has the potential to increase human exposure to these materials, but the impact of such exposure on human health is still unclear. One of the main routs of exposure is the respiratory tract, where alveolar epithelial cells present a vulnerable target at the interface with ambient air. Since the cellular interactions of NPs govern the cellular response and ultimately determine the impact on human health, our studies will help delineating relationships between particle properties and cellular interactions and response to better evaluate NP toxicity or biocompatibility. The Rutherford backscattered ion (RBI) is a helium ions imaging mode, which backscatters helium ions from every element except hydrogen, with a backscatter yield that depends on the atomic number of the target. Energy-sensitive backscatter analysis is being developed, which when combined with RBI image information, supports elemental identification at helium ion nanometer resolution. This capability will enable distinguishing NPs from cell surface structures with nanometer resolution.

  9. 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.

  10. Investigation of syngas interactions in alcohol synthesis catalyst

    SciTech Connect

    Akundi, M.A.

    1998-04-15

    The primary objectives of the project are to (a) synthesize, by controlled sequential and co-impregnation techniques, three distinct composition metal clusters (consisting of Cu-Co-Cr and Cu-Fe-Zn): rich in copper (Methanol selective), rich in ferromagnetic metal (Co or Fe-Hydrocarbon selective) and intermediate range (mixed alcohol catalysts); (b) investigate the changes in the magnetic character of the systems due to interaction with CO, through Zero-field Nuclear Magnetic Resonance (ZFNMR) study of cobalt and Magnetic character (saturation magnetization and coercive field) analysis of the composite catalyst of Vibrating Sample Magnetometry (VSM); (c) examine the changes in syngas adsorption character of the catalyst as the composition changes, by FTIR Spectroscopic analysis of CO stretching frequencies; (d) determine the nature and size of these intermetallic clusters by Scanning Electron Microscopy (SEM); and (e) perform catalytic runs on selected samples and analyze the correlations between the physical and chemical characteristics. The catalysts chosen have a greater promise for industrial application than the Rh and Mo based catalysts. Several groups preparing catalysts by synthetic routes have reported divergent results for activity and selectivity. Generally the research has followed an empirical path and less effort is devoted to analyze the mechanisms and the scientific basis. The primary intent of this study is to analyze the nature of the intermetallic and gas-metal interactions and examine the correlations to catalytic properties.

  11. Raman scattering investigation of VOCs in interaction with ice particles

    NASA Astrophysics Data System (ADS)

    Facq, Sébastien; Oancea, Adriana; Focsa, Cristian; Chazallon, Bertrand

    2010-05-01

    Cirrus clouds that form in the Earth's upper troposphere (UT) are known to play a significant role in the radiation budget and climate [1]. These clouds that cover about 35% of the Earth's surface [2] are mainly composed of small ice particles that can provide surfaces for trace gas interactions [3]. Volatile Organic Compounds (VOCs) are present in relative high abundance in the UT [4][5]. They promote substantial sources of free OH radicals that are responsible for driving photochemical cycles in the atmosphere. Their presence can both influence the oxidizing capacity and the ozone budget of the atmosphere. VOCs can interact with ice particles via different trapping processes (adsorption, diffusion, freezing, and co-deposition, i.e., incorporation of trace gases during growing ice conditions) which can result in the perturbation of the chemistry and photochemistry of the UT. Knowledge of the incorporation processes of VOCs in ice particles is important in order to understand and predict their impact on the ice particles structure and reactivity and more generally on the cirrus cloud formation. This proceeds via the in-situ characterization of the ice condensed phase in a pressure and temperature range of the UT. An important mechanism of UT cirrus cloud formation is the heterogeneous ice freezing process. In this study, we examine and characterize the interaction of a VOC, i.e., ethanol (EtOH) with ice particles during freezing. Vibrational spectra of water O-H and EtOH C-H spectral regions are analysed using confocal micro-Raman spectroscopy. Information at the molecular level on the surface structure can be derived from accompanying changes observed in band shapes and vibrational mode frequencies. Depending of the EtOH content, different crystalline phases have been identified and compared to hydrates previously reported for the EtOH-water system. Particular attention is paid on the effect of EtOH aqueous solutions cooling rate and droplet sizes on the phases

  12. Investigation on interaction of prulifloxacin with pepsin: A spectroscopic analysis

    NASA Astrophysics Data System (ADS)

    Huang, Yabei; Yan, Jie; Liu, Benzhi; Yu, Zhang; Gao, Xiaoyan; Tang, Yingcai; Zi, Yanqin

    2010-03-01

    The interaction between prulifloxacin, a kind of new oral taking antibiotic and pepsin, a kind of enzyme in the stomach has been investigated in vitro under a simulated physiological condition by different spectroscopic methods. The intrinsic fluorescence of pepsin was strongly quenched by prulifloxacin. This effect was rationalized in terms of a static quenching procedure. The binding parameters have been evaluated by fluorescence quenching methods. The negative value of Δ G0 reveals that the binding process is a spontaneous process. The binding distance R between donor (pepsin) and acceptor (prulifloxacin) was obtained according to the Förster's resonance energy transfer theory and found to be 0.95 nm. The results obtained herein will be of biological significance in pharmacology and clinical medicine.

  13. Investigating Molecular Hydrogen in Active Regions with IRIS

    NASA Astrophysics Data System (ADS)

    Jaeggli, Sarah A.; Saar, Steven H.; Daw, Adrian N.; Innes, Davina

    2014-06-01

    Molecular hydrogen should be the most abundant molecular species in sunspots, but recent observations with IRIS show that its florescent signature is absent from above the sunspot umbra, but appears brightly during flares. In this poster we continue the analysis of FUV observations of H2 in active regions, examining the correlation between the intensity of the H2 lines and the lines of C II and Si IV which are responsible for their excitation. We particularly focus on differentiating places where H2 is abundant, holes in the chromospheric opacity where FUV photons can enter more deeply into the solar atmosphere, and places where the FUV radiation field is intense, as in flares.

  14. Helium defects interactions and mechanism of helium bubble growth in tungsten: A molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Li, Xiao-Chun; Liu, Yi-Nan; Yu, Yi; Luo, Guang-Nan; Shu, Xiaolin; Lu, Guang-Hong

    2014-08-01

    Molecular dynamics simulations have been performed to investigate the interactions between helium (He) and defects in tungsten (W). The binding energy between He and He cluster is shown to be positive, which increases with increasing He cluster size. Both the W self-interstitial atoms (SIAs) and the vacancy can promote the He cluster formation. The binding energies of a He, a vacancy and an SIA W to a He-vacancy cluster (HenVm) in W are also investigated, which depend on the n/m ratio. According to these results, we propose the formation and growth mechanism of He bubbles, which involves the procedures of He-vacancy cluster formation, the capturing of vacancies, then He atoms, and vacancies again. The mechanism provides a good reference to understand the initial stage of the He bubble formation and growth in W.

  15. Investigating Molecular Kinetics by Variationally Optimized Diffusion Maps.

    PubMed

    Boninsegna, Lorenzo; Gobbo, Gianpaolo; Noé, Frank; Clementi, Cecilia

    2015-12-01

    Identification of the collective coordinates that describe rare events in complex molecular transitions such as protein folding has been a key challenge in the theoretical molecular sciences. In the Diffusion Map approach, one assumes that the molecular configurations sampled have been generated by a diffusion process, and one uses the eigenfunctions of the corresponding diffusion operator as reaction coordinates. While diffusion coordinates (DCs) appear to provide a good approximation to the true dynamical reaction coordinates, they are not parametrized using dynamical information. Thus, their approximation quality could not, as yet, be validated, nor could the diffusion map eigenvalues be used to compute relaxation rate constants of the system. Here we combine the Diffusion Map approach with the recently proposed Variational Approach for Conformation Dynamics (VAC). Diffusion Map coordinates are used as a basis set, and their optimal linear combination is sought using the VAC, which employs time-correlation information on the molecular dynamics (MD) trajectories. We have applied this approach to ultra-long MD simulations of the Fip35 WW domain and found that the first DCs are indeed a good approximation to the true reaction coordinates of the system, but they could be further improved using the VAC. Using the Diffusion Map basis, excellent approximations to the relaxation rates of the system are obtained. Finally, we evaluate the quality of different metric spaces and find that pairwise minimal root-mean-square deviation performs poorly, while operating in the recently introduced kinetic maps based on the time-lagged independent component analysis gives the best performance.

  16. Polymorphism and disorder in caffeine: Dielectric investigation of molecular mobilities

    NASA Astrophysics Data System (ADS)

    Descamps, M.; Decroix, A. A.

    2014-12-01

    Using dielectric relaxation data we have characterized the molecular mobilities of caffeine both in phase I (stable and metastable) and in phase II. In phase I effects of sublimation and phase transformation kinetics were carefully considered. In plane rotational motions were followed on a wide temperature range. A noticeable antiferroelectric short range order developing at the approach of the glass-like transition is characterized. Condition for occurrence of a critical-like behaviour is discussed. At high temperature the emergence of an additional ultra slow relaxation process is highlighted. Possible molecular mechanisms are proposed for both processes. In phase II the existence of a less intense relaxation process is confirmed. Close similarity with the main process developing in phase I hints at a common origin of the dipolar motions. Careful consideration of recent structure determinations leads to suggest that this process is associated to similar molecular in plane rotations but developing at the surface of crystalline samples. Lower cooperativity at the surface is reflected in the smaller activation entropy of the relaxation.

  17. Investigation of the hybrid molecular probe for intracellular studies

    PubMed Central

    Martinez, Karen; Medley, Colin D.; Yang, Chaoyong James; Tan, Weihong

    2009-01-01

    Monitoring gene expression in vivo is essential to the advancement of biological studies, medical diagnostics, and drug discovery. Adding to major efforts in developing molecular probes for mRNA monitoring, we have recently developed an alternative tool, the hybrid molecular probe (HMP). To optimize the probe, a series of experiments were performed to study the properties of HMP hybridization kinetics and stability. The results demonstrated the potential of the HMP as a prospective tool for use in both hybridization studies and in vitro and in vivo analyses. The HMP has shown no tendency to produce false positive signals, which is a major concern for living cell studies. Moreover, HMP has shown the ability to detect the mRNA expression of different genes inside single cells from both basal and stimulated genes. As an effective alternative to conventional molecular probes, the proven sensitivity, simplicity, and stability of HMPs show promise for their use in monitoring mRNA expression in living cells. PMID:18421445

  18. Phase equilibrium calculations of ternary liquid mixtures with binary interaction parameters and molecular size parameters determined from molecular dynamics.

    PubMed

    Oh, Suk Yung; Bae, Young Chan

    2010-07-15

    The method presented in this paper was developed to predict liquid-liquid equilibria in ternary liquid mixtures by using a combination of a thermodynamic model and molecular dynamics simulations. In general, common classical thermodynamic models have many parameters which are determined by fitting a model with experimental data. This proposed method, however, provides a simple procedure for calculating liquid-liquid equilibria utilizing binary interaction parameters and molecular size parameters determined from molecular dynamics simulations. This method was applied to mixtures containing water, hydrocarbons, alcohols, chlorides, ketones, acids, and other organic liquids over various temperature ranges. The predicted results agree well with the experimental data without the use of adjustable parameters.

  19. Investigation of polarization effects in the gramicidin A channel from ab initio molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Timko, Jeff; Kuyucak, Serdar

    2012-11-01

    Polarization is an important component of molecular interactions and is expected to play a particularly significant role in inhomogeneous environments such as pores and interfaces. Here we investigate the effects of polarization in the gramicidin A ion channel by performing quantum mechanics/molecular mechanics molecular dynamics (MD) simulations and comparing the results with those obtained from classical MD simulations with non-polarizable force fields. We consider the dipole moments of backbone carbonyl groups and channel water molecules as well as a number of structural quantities of interest. The ab initio results show that the dipole moments of the carbonyl groups and water molecules are highly sensitive to the hydrogen bonds (H-bonds) they participate in. In the absence of a K+ ion, water molecules in the channel are quite mobile, making the H-bond network highly dynamic. A central K+ ion acts as an anchor for the channel waters, stabilizing the H-bond network and thereby increasing their average dipole moments. In contrast, the K+ ion has little effect on the dipole moments of the neighboring carbonyl groups. The weakness of the ion-peptide interactions helps to explain the near diffusion-rate conductance of K+ ions through the channel. We also address the sampling issue in relatively short ab initio MD simulations. Results obtained from a continuous 20 ps ab initio MD simulation are compared with those generated by sampling ten windows from a much longer classical MD simulation and running each window for 2 ps with ab initio MD. Both methods yield similar results for a number of quantities of interest, indicating that fluctuations are fast enough to justify the short ab initio MD simulations.

  20. Investigation of polarization effects in the gramicidin A channel from ab initio molecular dynamics simulations.

    PubMed

    Timko, Jeff; Kuyucak, Serdar

    2012-11-28

    Polarization is an important component of molecular interactions and is expected to play a particularly significant role in inhomogeneous environments such as pores and interfaces. Here we investigate the effects of polarization in the gramicidin A ion channel by performing quantum mechanics/molecular mechanics molecular dynamics (MD) simulations and comparing the results with those obtained from classical MD simulations with non-polarizable force fields. We consider the dipole moments of backbone carbonyl groups and channel water molecules as well as a number of structural quantities of interest. The ab initio results show that the dipole moments of the carbonyl groups and water molecules are highly sensitive to the hydrogen bonds (H-bonds) they participate in. In the absence of a K(+) ion, water molecules in the channel are quite mobile, making the H-bond network highly dynamic. A central K(+) ion acts as an anchor for the channel waters, stabilizing the H-bond network and thereby increasing their average dipole moments. In contrast, the K(+) ion has little effect on the dipole moments of the neighboring carbonyl groups. The weakness of the ion-peptide interactions helps to explain the near diffusion-rate conductance of K(+) ions through the channel. We also address the sampling issue in relatively short ab initio MD simulations. Results obtained from a continuous 20 ps ab initio MD simulation are compared with those generated by sampling ten windows from a much longer classical MD simulation and running each window for 2 ps with ab initio MD. Both methods yield similar results for a number of quantities of interest, indicating that fluctuations are fast enough to justify the short ab initio MD simulations.

  1. In-plane Van der Waals interactions of molecular self-assembly monolayer

    NASA Astrophysics Data System (ADS)

    Gao, Hong-Ying; Wagner, Hendrik; Held, Philipp Alexander; Du, Shixuan; Gao, Hong-Jun; Studer, Armido; Fuchs, Harald

    2015-02-01

    We demonstrate that the Van der Waals interactions in plane are important to control molecular self-assembly structure as well their phase transition. Using precise chemical modification to mediate such in-plane cohesive interactions, we observed the spontaneous formations of 2D order or disorder molecular self-assembly structures, as well their order-disorder phase transitions by annealing. Interestingly, we identified that the side alkyl chains stand up at surfaces and form the `locked' pairs/windmill structures. Moreover, we realized the covalent coupling based on ethynyl functionality before molecular desorption from metal surfaces, by enhancing the in-plane interactions.

  2. Fire safety in space - Investigating flame spread interaction over wires

    NASA Astrophysics Data System (ADS)

    Citerne, Jean-Marie; Dutilleul, Hugo; Kizawa, Koki; Nagachi, Masashi; Fujita, Osamu; Kikuchi, Masao; Jomaas, Grunde; Rouvreau, Sébastien; Torero, Jose L.; Legros, Guillaume

    2016-09-01

    A new rig for microgravity experiments was used for the study flame spread of parallel polyethylene-coated wires in concurrent and opposed airflow. The parabolic flight experiments were conducted at small length- and time scales, i.e. typically over 10 cm long samples for up to 20 s. For the first time, the influence of neighboring spread on the mass burning rate was assessed in microgravity. The observations are contrasted with the influence characterized in normal gravity. The experimental results are expected to deliver meaningful guidelines for future, planned experiments at a larger scale. Arising from the current results, the issue of the potential interaction among spreading flames also needs to be carefully investigated as this interaction plays a major role in realistic fire scenarios, and therefore on the design of the strategies that would allow the control of such a fire. Once buoyancy has been removed, the characteristic length and time scales of the different modes of heat and mass transfer are modified. For this reason, interaction among spreading flames may be revealed in microgravity, while it would not at normal gravity, or vice versa. Furthermore, the interaction may lead to an enhanced spread rate when mutual preheating dominates or, conversely, a reduced spread rate when oxidizer flow vitiation is predominant. In more general terms, the current study supports both the SAFFIRE and the FLARE projects, which are large projects with international scientific teams. First, material samples will be tested in a series of flight experiments (SAFFIRE 1-3) conducted in Cygnus vehicles after they have undocked from the ISS. These experiments will allow the study of ignition and possible flame spread in real spacecraft conditions, i.e. over real length scale samples within real time scales. Second, concomitant research conducted within the FLARE project is dedicated to the assessment of new standard tests for materials that a spacecraft can be composed of

  3. Structural investigations on a linear isolated depsipeptide: the importance of dispersion interactions.

    PubMed

    Stamm, A; Bernhard, D; Gerhards, M

    2016-06-01

    In this paper we present the first investigations on an isolated linear depsipetide CyCO-Gly-Lac-NH-PhOMe (cyclohexylcarbonyl-glycine-lactate-2-anisidine abbreviated as MOC) in a molecular beam experiment. Depsipeptides are a special subclass of peptides which contain at least one ester bond replacing a peptide bond. This leads to a different folding behavior and a different biological activity compared to a "normal" peptide. In order to analyze the folding of an isolated depsipeptide on a molecular level a variety of combined IR/UV methods including IR/IR/UV experiments are applied to MOC. Three different isomers are identified in combination with DFT calculations using the hybrid functional B3LYP-D3 with a TZVP basis set. The most stable structure shows a tweezer-like arrangement between the aromatic chromophore and the aliphatic cyclohexyl ring. A characteristic feature of this structure is that it is stabilized by dispersion interactions resulting from CH/π interactions. If dispersion is not taken into account this structural arrangement is no longer a minimum on the potential energy surface indicating the importance of dispersion interactions.

  4. Radiative interactions in molecular gases under local and nonlocal thermodynamic equilibrium conditions

    NASA Technical Reports Server (NTRS)

    Tiwari, S. N.; Jha, M. K.

    1993-01-01

    Basic formulations, analyses, and numerical procedures are presented to investigate radiative heat interactions in diatomic and polyatomic gases under local and nonlocal thermodynamic equilibrium conditions. Essential governing equations are presented for both gray and nongray gases. Information is provided on absorption models, relaxation times, and transfer equations. Radiative flux equations are developed which are applicable under local and nonlocal thermodynamic equilibrium conditions. The problem is solved for fully developed laminar incompressible flows between two parallel plates under the boundary condition of a uniform surface heat flux. For specific applications, three diatomic and three polyatomic gases are considered. The results are obtained numerically by employing the method of variation of parameters. The results are compared under local and nonlocal thermodynamic equilibrium conditions at different temperature and pressure conditions. Both gray and nongray studies are conducted extensively for all molecular gases considered. The particular gases selected for this investigation are CO, NO, OH, CO2, H2O, and CH4. The temperature and pressure range considered are 300-2000 K and 0.1-10 atmosphere, respectively. In general, results demonstrate that the gray gas approximation overestimates the effect of radiative interaction for all conditions. The conditions of NLTE, however, result in underestimation of radiative interactions. The method developed for this study can be extended to solve complex problems of radiative heat transfer involving nonequilibrium phenomena.

  5. Molecular dynamics simulation of amorphous indomethacin-poly(vinylpyrrolidone) glasses: solubility and hydrogen bonding interactions.

    PubMed

    Xiang, Tian-Xiang; Anderson, Bradley D

    2013-03-01

    Amorphous drug dispersions are frequently employed to enhance solubility and dissolution of poorly water-soluble drugs and thereby increase their oral bioavailability. Because these systems are metastable, phase separation of the amorphous components and subsequent drug crystallization may occur during storage. Computational methods to determine the likelihood of these events would be very valuable, if their reliability could be validated. This study investigates amorphous systems of indomethacin (IMC) in poly(vinylpyrrolidone) (PVP) and their molecular interactions by means of molecular dynamics (MD) simulations. IMC and PVP molecules were constructed using X-ray diffraction data, and force-field parameters were assigned by analogy with similar groups in Amber-ff03. Five assemblies varying in PVP and IMC composition were equilibrated in their molten states then cooled at a rate of 0.03 K/ps to generate amorphous glasses. Prolonged aging dynamic runs (100 ns) at 298 K and 1 bar were then carried out, from which solubility parameters, the Flory-Huggins interaction parameter, and associated hydrogen bonding properties were obtained. Calculated glass transition temperature (T(g)) values were higher than experimental results because of the faster cooling rates in MD simulations. Molecular mobility as characterized by atomic fluctuations was substantially reduced below the T(g) with IMC-PVP systems exhibiting lower mobilities than that found in amorphous IMC, consistent with the antiplasticizing effect of PVP. The number of IMC-IMC hydrogen bonds (HBs) formed per IMC molecule was substantially lower in IMC-PVP mixtures, particularly the fractions of IMC molecules involved in two or three HBs with other IMC molecules that may be potential precursors for crystal growth. The loss of HBs between IMC molecules in the presence of PVP was largely compensated for by the formation of IMC-PVP HBs. The difference (6.5 MPa(1/2)) between the solubility parameters in amorphous IMC

  6. QSAR modeling and molecular interaction analysis of natural compounds as potent neuraminidase inhibitors.

    PubMed

    Sun, Jiaying; Mei, Hu

    2016-04-26

    Different QSAR models of 40 natural compounds as neuraminidase inhibitors (NIs) are developed to comprehend chemical-biological interactions and predict activities against neuraminidase (NA) from Clostridium perfringens. Based on the constitutional, topological and conformational descriptors, R(2) and Q(2) values of the obtained SRA model are 0.931 and 0.856. The R(2) and Q(2) values of the constructed HQSAR and almond models are 0.903 and 0.767, 0.904 and 0.511, respectively. Based on the pharmacophore alignment, R(2) and Q(2) values of the optimal CoMSIA model are 0.936 and 0.654. Moreover, Rtest(2) and Qext(2) of values of SRA, HQSAR, almond and CoMSIA models are 0.611 and 0.565, 0.753 and 0.750, 0.612 and 0.582, 0.582 and 0.571, respectively. So, QSAR models have good predictive capability. They can be further used to evaluate and screen new compounds. Moreover, hydrogen bonds and electrostatic factors have high contributions to activities. To understand molecular interactions between natural compounds and NA from Clostridium perfringens, molecular docking is investigated. The docking results elucidate that Arg266, Asp291, Asp328, Tyr485, Glu493, Arg555, Arg615 and Tyr655 are especially the key residues in the active site of 2bf6. Hydrogen bonds and electrostatics are key factors, which impact the interactions between NIs and NA. So, the influential factors of interactions between NIs and NA in the docking results are in agreement with the QSAR results. PMID:27008437

  7. Exploring the Molecular Design of Protein Interaction Sites with Molecular Dynamics Simulations and Free Energy Calculations†

    PubMed Central

    Liang, Shide; Li, Liwei; Hsu, Wei-Lun; Pilcher, Meaghan N.; Uversky, Vladimir; Zhou, Yaoqi; Dunker, A. Keith; Meroueh, Samy O.

    2009-01-01

    The significant work that has been invested toward understanding protein–protein interaction has not translated into significant advances in structure-based predictions. In particular redesigning protein surfaces to bind to unrelated receptors remains a challenge, partly due to receptor flexibility, which is often neglected in these efforts. In this work, we computationally graft the binding epitope of various small proteins obtained from the RCSB database to bind to barnase, lysozyme, and trypsin using a previously derived and validated algorithm. In an effort to probe the protein complexes in a realistic environment, all native and designer complexes were subjected to a total of nearly 400 ns of explicit-solvent molecular dynamics (MD) simulation. The MD data led to an unexpected observation: some of the designer complexes were highly unstable and decomposed during the trajectories. In contrast, the native and a number of designer complexes remained consistently stable. The unstable conformers provided us with a unique opportunity to define the structural and energetic factors that lead to unproductive protein–protein complexes. To that end we used free energy calculations following the MM-PBSA approach to determine the role of nonpolar effects, electrostatics and entropy in binding. Remarkably, we found that a majority of unstable complexes exhibited more favorable electrostatics than native or stable designer complexes, suggesting that favorable electrostatic interactions are not prerequisite for complex formation between proteins. However, nonpolar effects remained consistently more favorable in native and stable designer complexes reinforcing the importance of hydrophobic effects in protein–protein binding. While entropy systematically opposed binding in all cases, there was no observed trend in the entropy difference between native and designer complexes. A series of alanine scanning mutations of hot-spot residues at the interface of native and

  8. Investigation of imprinting parameters and their recognition nature for quinine-molecularly imprinted polymers

    NASA Astrophysics Data System (ADS)

    He, Jian-feng; Zhu, Quan-hong; Deng, Qin-ying

    2007-08-01

    A series of molecularly imprinted polymers (MIPs) was prepared using quinine as the template molecules by bulk polymerization. The presence of monomer-template solution complexes in non-covalent MIPs systems has been verified by both fluorescence and UV-vis spectrometric detection. The influence of different synthetic conditions (porogen, functional monomer, cross-linkers, initiation methods, monomer-template ratio, etc.) on recognition properties of the polymers was investigated. Scatchard analysis revealed that two classes of binding sites were formed in the imprinted polymer. The corresponding dissociation constants were estimated to be 45.00 μmol l -1 and 1.42 mmol l -1, respectively, by utilizing a multi-site recognition model. The binding characteristics of the imprinted polymers were explored in various solvents using equilibrium binding experiments. In the organic media, results suggested that polar interactions (hydrogen bonding, ionic interactions, etc.) between acidic monomer/polymer and template molecules were mainly responsible for the recognition, whereas in aqueous media, hydrophobic interactions had a remarkable non-specific contribution to the overall binding. The specificity of MIP was evaluated by rebinding the other structurally similar compounds. The results indicated that the imprinted polymers exhibited an excellent stereo-selectivity toward quinine.

  9. Investigation of deformation mechanisms of staggered nanocomposites using molecular dynamics

    NASA Astrophysics Data System (ADS)

    Mathiazhagan, S.; Anup, S.

    2016-08-01

    Biological materials with nanostructure of regularly or stair-wise staggered arrangements of hard platelets reinforced in a soft protein matrix have superior mechanical properties. Applications of these nanostructures to ceramic matrix composites could enhance their toughness. Using molecular dynamics simulations, mechanical behaviour of the bio-inspired nanocomposites is studied. Regularly staggered model shows better flow behaviour compared to stair-wise staggered model due to the symmetrical crack propagation along the interface. Though higher stiffness and strength are obtained for stair-wise staggered models, rapid crack propagation reduces the toughness. Arresting this crack propagation could lead to superior mechanical properties in stair-wise staggered models.

  10. Spectroscopic and molecular docking studies on the interaction of the drug olanzapine with calf thymus DNA

    NASA Astrophysics Data System (ADS)

    Shahabadi, Nahid; Bagheri, Somayeh

    2015-02-01

    The present study investigated the binding interaction between olanzapine and calf thymus DNA (ct-DNA) using emission, absorption, circular dichroism, viscosity measurements and molecular modeling. Thermodynamic parameters (ΔH < 0 and ΔS < 0) indicated that hydrogen bond and van der Waals play main roles in the binding of the drug to ct-DNA. Spectrophotometric studies of the interaction of olanzapine with DNA have shown that it could bind to ct-DNA (Kb = 2 × 103 M-1). The binding constant is comparable to standard groove binding drugs. Competitive fluorimetric studies with Hoechst 33258 have shown that olanzapine exhibits the ability to displace the DNA-bound Hoechst 33258 indicating that binds strongly in minor groove of DNA helix. Furthermore, the drug induces detectable changes in the CD spectrum of ct-DNA as well as changes in its viscosity. All of the experimental results prove that the groove binding must be predominant. The results obtained from experimental data were in good agreement with molecular modeling studies.

  11. Controlling Intramolecular Conformation through Nonbonding Interaction for Soft-Conjugated Materials: Molecular Design and Optoelectronic Properties.

    PubMed

    Cheng, Yuanfang; Qi, Yuanyuan; Tang, Yuting; Zheng, Chao; Wan, Yifang; Huang, Wei; Chen, Runfeng

    2016-09-15

    To address the intrinsic contradiction between high optoelectronic properties and good processability in organic π-conjugated molecules, we propose that soft-conjugated molecules (SCMs), conformationally locked by intramolecular nonbonding interactions, can benefit from both nonplanar molecular structures in solution for processing and rigid coplanar structures in the solid state for enhanced optoelectronic properties. Computational results reveal that nonbonding pairs of S···N, N···H, and F···S are strong enough to prevail over thermal fluctuations, steric effects, and other repulsive interactions to force the adjacent aromatic rings to be planar; thus, constructed SCMs display delocalized frontier molecular orbitals with frontier orbital energy levels, band gaps, reorganization energies, and photophyscial properties comparable to those of rigid-conjugated molecules because of their stable planar soft-conjugation at both ground and excited states. The understanding gained from the theoretical investigations of SCMs provides keen insights into construction and modification of soft-conjugations to harmonize the optoelectronic property and processability in conjugated molecules for advanced optoelectronic applications. PMID:27569364

  12. Controlling Intramolecular Conformation through Nonbonding Interaction for Soft-Conjugated Materials: Molecular Design and Optoelectronic Properties.

    PubMed

    Cheng, Yuanfang; Qi, Yuanyuan; Tang, Yuting; Zheng, Chao; Wan, Yifang; Huang, Wei; Chen, Runfeng

    2016-09-15

    To address the intrinsic contradiction between high optoelectronic properties and good processability in organic π-conjugated molecules, we propose that soft-conjugated molecules (SCMs), conformationally locked by intramolecular nonbonding interactions, can benefit from both nonplanar molecular structures in solution for processing and rigid coplanar structures in the solid state for enhanced optoelectronic properties. Computational results reveal that nonbonding pairs of S···N, N···H, and F···S are strong enough to prevail over thermal fluctuations, steric effects, and other repulsive interactions to force the adjacent aromatic rings to be planar; thus, constructed SCMs display delocalized frontier molecular orbitals with frontier orbital energy levels, band gaps, reorganization energies, and photophyscial properties comparable to those of rigid-conjugated molecules because of their stable planar soft-conjugation at both ground and excited states. The understanding gained from the theoretical investigations of SCMs provides keen insights into construction and modification of soft-conjugations to harmonize the optoelectronic property and processability in conjugated molecules for advanced optoelectronic applications.

  13. Molecular dynamics simulation and NMR investigation of the association of the β-blockers atenolol and propranolol with a chiral molecular micelle

    NASA Astrophysics Data System (ADS)

    Morris, Kevin F.; Billiot, Eugene J.; Billiot, Fereshteh H.; Hoffman, Charlene B.; Gladis, Ashley A.; Lipkowitz, Kenny B.; Southerland, William M.; Fang, Yayin

    2015-08-01

    Molecular dynamics simulations and NMR spectroscopy were used to compare the binding of two β-blocker drugs to the chiral molecular micelle poly-(sodium undecyl-(L)-leucine-valine). The molecular micelle is used as a chiral selector in capillary electrophoresis. This study is part of a larger effort to understand the mechanism of chiral recognition in capillary electrophoresis by characterizing the molecular micelle binding of chiral compounds with different geometries and charges. Propranolol and atenolol were chosen because their structures are similar, but their chiral interactions with the molecular micelle are different. Molecular dynamics simulations showed both propranolol enantiomers inserted their aromatic rings into the molecular micelle core and that (S)-propranolol associated more strongly with the molecular micelle than (R)-propranolol. This difference was attributed to stronger molecular micelle hydrogen bonding interactions experienced by (S)-propranolol. Atenolol enantiomers were found to bind near the molecular micelle surface and to have similar molecular micelle binding free energies.

  14. Carbon Dioxide - rock interaction: from molecular observations to theorised interactions in fluid-rock systems

    NASA Astrophysics Data System (ADS)

    Calcara, Massimo; Borgia, Andrea

    2013-04-01

    Current global warming theories have produced some benefits: among them, detailed studies on CO2 and its properties, possible applications and perspectives. Starting from its use as a "green solvent" (for instance in decaffeination process), to enhance system in oil recovery, to capture and storage enough amount of CO2 in geological horizon. So, a great debate is centred around this molecule. One More useful research in natural horizon studies is its theorised use in Enhanced Geothermal Systems with CO2 as the only working fluid. In any case, the CO2 characteristics should be deeply understood, before injecting a molecule prone to change easily its aggregation state at relatively shallow depth. CO2 Rock interaction becomes therefore a focal point in approaching research sectors linked in some manner to natural or induced presence of carbon dioxide in geological horizons. Possible chemical interactions between fluids and solids have always been a central topic in defining evolution of the system as a whole in terms of dissolutions, reactions, secondary mineral formation and, in case of whichever plant, scaling. Questions arise in case of presence of CO2 with host rocks. Chemical and molecular properties are strategic. CO2 Rock interactions are based on eventual solubility capability of pure liquid and supercritical CO2 seeking and eventually quantifying its polar and/or ionic solvent capabilities. Single molecule at STP condition is linear, with central carbon atom and oxygen atoms at opposite site on a straight line with a planar angle. It has a quadrupolar moment due to the electronegativity difference between carbon and oxygen. As soon as CO2 forms bond with water, it deforms even at atmospheric pressure, assuming an induced dipole moment with a value around 0.02 Debye. Hydrated CO2 forms a hydrophilic bond; it deforms with an angle of 178 degrees. Pure CO2 forms self aggregates. In the simplest case a dimer, with two molecules of CO2 exerting mutual attraction

  15. Investigation of molecular penetration depth variation with SMBI fluxes

    NASA Astrophysics Data System (ADS)

    Zhou, Yu-Lin; Wang, Zhan-Hui; Xu, Min; Wang, Qi; Nie, Lin; Feng, Hao; Sun, Wei-Guo

    2016-09-01

    We study the molecular penetration depth variation with the SMBI fluxes. The molecular transport process and the penetration depth during SMBI with various injection velocities and densities are simulated and compared. It is found that the penetration depth of molecules strongly depends on the radial convective transport of SMBI and it increases with the increase of the injection velocity. The penetration depth does not vary much once the SMBI injection density is larger than a critical value due to the dramatic increase of the dissociation rate on the fueling path. An effective way to improve the SMBI penetration depth has been predicted, which is SMBI with a large radial injection velocity and a lower molecule injection density than the critical density. Project supported by the National Natural Science Foundation of China (Grant Nos. 11375053, 11575055, 11405022, and 11405112), the Chinese National Fusion Project for ITER (Grant Nos. 2013GB107001 and 2013GB112005), the International S&T Cooperation Program of China (Grant No. 2015DFA61760), and the Funds of the Youth Innovation Team of Science and Technology in Sichuan Province of China (Grant No. 2014TD0023).

  16. Investigation of molecular penetration depth variation with SMBI fluxes

    NASA Astrophysics Data System (ADS)

    Zhou, Yu-Lin; Wang, Zhan-Hui; Xu, Min; Wang, Qi; Nie, Lin; Feng, Hao; Sun, Wei-Guo

    2016-09-01

    We study the molecular penetration depth variation with the SMBI fluxes. The molecular transport process and the penetration depth during SMBI with various injection velocities and densities are simulated and compared. It is found that the penetration depth of molecules strongly depends on the radial convective transport of SMBI and it increases with the increase of the injection velocity. The penetration depth does not vary much once the SMBI injection density is larger than a critical value due to the dramatic increase of the dissociation rate on the fueling path. An effective way to improve the SMBI penetration depth has been predicted, which is SMBI with a large radial injection velocity and a lower molecule injection density than the critical density. Project supported by the National Natural Science Foundation of China (Grant Nos. 11375053, 11575055, 11405022, and 11405112), the Chinese National Fusion Project for ITER (Grant Nos. 2013GB107001 and 2013GB112005), the International S&T Cooperation Program of China (Grant No. 2015DFA61760), and the Funds of the Youth Innovation Team of Science and Technology in Sichuan Province of China (Grant No. 2014TD0023).

  17. RNA polymerase molecular beacon as tool for studies of RNA polymerase-promoter interactions.

    PubMed

    Mekler, Vladimir; Severinov, Konstantin

    2015-09-15

    The molecular details of formation of transcription initiation complex upon the interaction of bacterial RNA polymerase (RNAP) with promoters are not completely understood. One way to address this problem is to understand how RNAP interacts with different parts of promoter DNA. A recently developed fluorometric RNAP molecular beacon assay allows one to monitor the RNAP interactions with various unlabeled DNA probes and quantitatively characterize partial RNAP-promoter interactions. This paper focuses on methodological aspects of application of this powerful assay to study the mechanism of transcription initiation complex formation by Escherichia coli RNA polymerase σ(70) holoenzyme and its regulation by bacterial and phage encoded factors.

  18. RNA polymerase molecular beacon as tool for studies of RNA polymerase - promoter interactions

    PubMed Central

    Mekler, Vladimir; Severinov, Konstantin

    2015-01-01

    The molecular details of formation of transcription initiation complex upon the interaction of bacterial RNA polymerase (RNAP) with promoters are not completely understood. One way to address this problem is to understand how RNAP interacts with different parts of promoter DNA. A recently developed fluorometric RNAP molecular beacon assay allows one to monitor the RNAP interactions with various unlabeled DNA probes and quantitatively characterize partial RNAP-promoter interactions. This paper focuses on methodological aspects of application of this powerful assay to study the mechanism of transcription initiation complex formation by Escherichia coli RNA polymerase σ70 holoenzyme and its regulation by bacterial and phage encoded factors. PMID:25956222

  19. A molecular-genetic approach to studying source-sink interactions in Arabidopsis thalian. Final report

    SciTech Connect

    Gibson, S. I.

    2000-06-01

    This is a final report describing the results of the research funded by the DOE Energy Biosciences Program grant entitled ''A Molecular-Genetic Approach to Studying Source-Sink Interactions in Arabidiopsis thaliana''.

  20. Relationship between molecular weight of poly(ethylene)glycol and intermolecular interaction of Taka-amylase A monomers

    NASA Astrophysics Data System (ADS)

    Onuma, Kazuo; Furubayashi, Naoki; Shibata, Fujiko; Kobayashi, Yoshiko; Kaito, Sachiko; Ohnishi, Yuki; Inaka, Koji

    2010-04-01

    Dynamic and static light scattering investigations of Taka-amylase A (TAA) protein monomers were done using solutions containing poly(ethylene)glycol (PEG) with molecular weights of 1500, 4000, 8000, and 20 000. The anomalies observed in a previous study using a weight of 8000, in which the hydrodynamic TAA monomer radius at a zero protein concentration and the molecular weight of the monomers decreased when the PEG concentration was increased, were observed for all four weights. These anomalies became more pronounced as the PEG molecular weight was increased. The overall interaction parameter did not move further in the direction of the attractive force despite an increase in the PEG concentration from 6% to 12.5% for the PEG 8000 and 20 000 solutions. This was due to the change in the relative contributions of the static structure factor (direct interaction) and the hydrodynamic interaction factor (indirect interaction) against the overall interaction parameter. For the PEG 1500 and 4000 solutions, the change in the overall interaction parameter with an increase in the PEG concentration was controlled by changing the static structure factor. For the PEG 8000 and 20 000 solutions, a change in the hydrodynamic interaction factor with an increase in the PEG concentration offset the change in the static structure factor, unexpectedly resulting in the overall interaction parameter being independent of the PEG concentration. This suggests that the scale and density of a PEG network structure, which are thought to be the origin of the observed anomalies, change nonlinearly with the PEG molecular weight.

  1. Challenges and novel approaches for investigating molecular mediation

    PubMed Central

    Richmond, R.C.; Hemani, G.; Tilling, K.; Davey Smith, G.; Relton, C.L.

    2016-01-01

    Understanding mediation is useful for identifying intermediates lying between an exposure and an outcome which, when intervened upon, will block (some or all of) the causal pathway between the exposure and outcome. Mediation approaches used in conventional epidemiology have been adapted to understanding the role of molecular intermediates in situations of high-dimensional omics data with varying degrees of success. In particular, the limitations of observational epidemiological study including confounding, reverse causation and measurement error can afflict conventional mediation approaches and may lead to incorrect conclusions regarding causal effects. Solutions to analysing mediation which overcome these problems include the use of instrumental variable methods such as Mendelian randomization, which may be applied to evaluate causality in increasingly complex networks of omics data. PMID:27439390

  2. Molecular simulations of lipid-mediated protein-protein interactions.

    PubMed

    de Meyer, Frédérick Jean-Marie; Venturoli, Maddalena; Smit, Berend

    2008-08-01

    Recent experimental results revealed that lipid-mediated interactions due to hydrophobic forces may be important in determining the protein topology after insertion in the membrane, in regulating the protein activity, in protein aggregation and in signal transduction. To gain insight into the lipid-mediated interactions between two intrinsic membrane proteins, we developed a mesoscopic model of a lipid bilayer with embedded proteins, which we studied with dissipative particle dynamics. Our calculations of the potential of mean force between transmembrane proteins show that hydrophobic forces drive long-range protein-protein interactions and that the nature of these interactions depends on the length of the protein hydrophobic segment, on the three-dimensional structure of the protein and on the properties of the lipid bilayer. To understand the nature of the computed potentials of mean force, the concept of hydrophilic shielding is introduced. The observed protein interactions are interpreted as resulting from the dynamic reorganization of the system to maintain an optimal hydrophilic shielding of the protein and lipid hydrophobic parts, within the constraint of the flexibility of the components. Our results could lead to a better understanding of several membrane processes in which protein interactions are involved. PMID:18487292

  3. Molecular investigation into outbreak of HIV in a Scottish prison.

    PubMed Central

    Yirrell, D. L.; Robertson, P.; Goldberg, D. J.; McMenamin, J.; Cameron, S.; Leigh Brown, A. J.

    1997-01-01

    OBJECTIVES: To support already established epidemiological links between inmates of Glenochil prison positive for HIV infection by using molecular techniques and thus provide evidence of the extent of acquisition during a recent outbreak of the disease resulting from needle sharing. To identify possible sources of the outbreak, and to demonstrate the ability of the methodology to make further links beyond the original outbreak. DESIGN: Viral sequences obtained from the blood of HIV positive prisoners previously identified by standard epidemiological methods were compared with each other and with sequences from other Scottish patients. SETTING: Glenochil prison for men, central Scotland. SUBJECTS: Adult inmates and their possible contacts. RESULTS: Phylogenetic analysis of viral sequences in two different genomic regions showed that 13 of the 14 HIV positive prisoners had been infected from a common source. Previous research had shown that six of these had acquired their infection in Glenochil; molecular evidence suggests that more than double this number were infected while incarcerated. Virus from two long term HIV positive patients who were in the prison at the time of the outbreak but who were not identified in the original or subsequent surveys was sufficiently different to make it unlikely that they were the source. A viral sequence from heterosexual transmission from one inmate showed the ability of these techniques to follow the infection through different routes of infection. CONCLUSION: The number of prisoners infected with HIV during the 1993 outbreak within Glenochil prison was more than twice that previously shown. This shows the potential for the spread of bloodborne diseases within prisons by injecting drugs. PMID:9167560

  4. Influence of molecular shape, conformability, net surface charge, and tissue interaction on transscleral macromolecular diffusion.

    PubMed

    Srikantha, Nishanthan; Mourad, Fatma; Suhling, Klaus; Elsaid, Naba; Levitt, James; Chung, Pei Hua; Somavarapu, Satyanarayana; Jackson, Timothy L

    2012-09-01

    The purpose of this study was to investigate the influence of molecular shape, conformability, net surface charge and tissue interaction on transscleral diffusion. Unfixed, porcine sclera was clamped in an Ussing chamber. Fluorophore-labelled neutral albumin, neutral dextran, or neutral ficoll were placed in one hemi-chamber and the rate of transscleral diffusion was measured over 24 h using a spectrophotometer. Experiments were repeated using dextrans and ficoll with positive or negative net surface charges. Fluorescence recovery after photobleaching (FRAP) was undertaken to compare transscleral diffusion with diffusion through a solution. All molecules were 70 kDa. With FRAP, the diffusion coefficient (D) of neutral molecules was highest for albumin, followed by ficoll, then dextran (p < 0.0001). Positive dextrans diffused fastest, followed by negative, then neutral dextrans (p = 0.0004). Neutral ficoll diffused the fastest, followed by positive then negative ficoll (p = 0.5865). For the neutral molecules, transscleral D was highest for albumin, followed by dextran, then ficoll (p < 0.0001). D was highest for negative ficoll, followed by neutral, then positive ficoll (p < 0.0001). By contrast, D was highest for positive dextran, followed by neutral, then negative dextran (p = 0.0021). In conclusion, diffusion in free solution does not predict transscleral diffusion and the molecular-tissue interaction is important. Molecular size, shape, and charge may all markedly influence transscleral diffusion, as may conformability to a lesser degree, but their effects may be diametrically opposed in different molecules, and their influence on diffusion is more complex than previously thought. Each variable cannot be considered in isolation, and the interplay of all these variables needs to be tested, when selecting or designing drugs for transscleral delivery. PMID:22846670

  5. Molecular interactions between the olive and the fruit fly Bactrocera oleae

    PubMed Central

    2012-01-01

    Background The fruit fly Bactrocera oleae is the primary biotic stressor of cultivated olives, causing direct and indirect damages that significantly reduce both the yield and the quality of olive oil. To study the olive-B. oleae interaction, we conducted transcriptomic and proteomic investigations of the molecular response of the drupe. The identifications of genes and proteins involved in the fruit response were performed using a Suppression Subtractive Hybridisation technique and a combined bi-dimensional electrophoresis/nanoLC-ESI-LIT-MS/MS approach, respectively. Results We identified 196 ESTs and 26 protein spots as differentially expressed in olives with larval feeding tunnels. A bioinformatic analysis of the identified non-redundant EST and protein collection indicated that different molecular processes were affected, such as stress response, phytohormone signalling, transcriptional control and primary metabolism, and that a considerable proportion of the ESTs could not be classified. The altered expression of 20 transcripts was also analysed by real-time PCR, and the most striking differences were further confirmed in the fruit of a different olive variety. We also cloned the full-length coding sequences of two genes, Oe-chitinase I and Oe-PR27, and showed that these are wound-inducible genes and activated by B. oleae punctures. Conclusions This study represents the first report that reveals the molecular players and signalling pathways involved in the interaction between the olive fruit and its most damaging biotic stressor. Drupe response is complex, involving genes and proteins involved in photosynthesis as well as in the production of ROS, the activation of different stress response pathways and the production of compounds involved in direct defence against phytophagous larvae. Among the latter, trypsin inhibitors should play a major role in drupe resistance reaction. PMID:22694925

  6. Influence of molecular shape, conformability, net surface charge, and tissue interaction on transscleral macromolecular diffusion.

    PubMed

    Srikantha, Nishanthan; Mourad, Fatma; Suhling, Klaus; Elsaid, Naba; Levitt, James; Chung, Pei Hua; Somavarapu, Satyanarayana; Jackson, Timothy L

    2012-09-01

    The purpose of this study was to investigate the influence of molecular shape, conformability, net surface charge and tissue interaction on transscleral diffusion. Unfixed, porcine sclera was clamped in an Ussing chamber. Fluorophore-labelled neutral albumin, neutral dextran, or neutral ficoll were placed in one hemi-chamber and the rate of transscleral diffusion was measured over 24 h using a spectrophotometer. Experiments were repeated using dextrans and ficoll with positive or negative net surface charges. Fluorescence recovery after photobleaching (FRAP) was undertaken to compare transscleral diffusion with diffusion through a solution. All molecules were 70 kDa. With FRAP, the diffusion coefficient (D) of neutral molecules was highest for albumin, followed by ficoll, then dextran (p < 0.0001). Positive dextrans diffused fastest, followed by negative, then neutral dextrans (p = 0.0004). Neutral ficoll diffused the fastest, followed by positive then negative ficoll (p = 0.5865). For the neutral molecules, transscleral D was highest for albumin, followed by dextran, then ficoll (p < 0.0001). D was highest for negative ficoll, followed by neutral, then positive ficoll (p < 0.0001). By contrast, D was highest for positive dextran, followed by neutral, then negative dextran (p = 0.0021). In conclusion, diffusion in free solution does not predict transscleral diffusion and the molecular-tissue interaction is important. Molecular size, shape, and charge may all markedly influence transscleral diffusion, as may conformability to a lesser degree, but their effects may be diametrically opposed in different molecules, and their influence on diffusion is more complex than previously thought. Each variable cannot be considered in isolation, and the interplay of all these variables needs to be tested, when selecting or designing drugs for transscleral delivery.

  7. Investigating joint attention mechanisms through spoken human-robot interaction.

    PubMed

    Staudte, Maria; Crocker, Matthew W

    2011-08-01

    Referential gaze during situated language production and comprehension is tightly coupled with the unfolding speech stream (Griffin, 2001; Meyer, Sleiderink, & Levelt, 1998; Tanenhaus, Spivey-Knowlton, Eberhard, & Sedivy, 1995). In a shared environment, utterance comprehension may further be facilitated when the listener can exploit the speaker's focus of (visual) attention to anticipate, ground, and disambiguate spoken references. To investigate the dynamics of such gaze-following and its influence on utterance comprehension in a controlled manner, we use a human-robot interaction setting. Specifically, we hypothesize that referential gaze is interpreted as a cue to the speaker's referential intentions which facilitates or disrupts reference resolution. Moreover, the use of a dynamic and yet extremely controlled gaze cue enables us to shed light on the simultaneous and incremental integration of the unfolding speech and gaze movement. We report evidence from two eye-tracking experiments in which participants saw videos of a robot looking at and describing objects in a scene. The results reveal a quantified benefit-disruption spectrum of gaze on utterance comprehension and, further, show that gaze is used, even during the initial movement phase, to restrict the spatial domain of potential referents. These findings more broadly suggest that people treat artificial agents similar to human agents and, thus, validate such a setting for further explorations of joint attention mechanisms.

  8. Investigating hard sphere interactions through spin echo scattering angle measurement

    NASA Astrophysics Data System (ADS)

    Washington, Adam

    Spin Echo Scattering Angle Measurement (SESAME) allows neutron scattering instruments to perform real space measurements on large micron scale samples by encoding the scattering angle into the neutron's spin state via Larmor precession. I have built a SESAME instrument at the Low Energy Neutron Source. I have also assisted in the construction of a modular SESAME instrument on the ASTERIX beamline at Los Alamos National lab. The ability to tune these instruments has been proved mathematically and optimized and automated experimentally. Practical limits of the SESAME technique with respect to polarization analyzers, neutron spectra, Larmor elements, and data analysis were investigated. The SESAME technique was used to examine the interaction of hard spheres under depletion. Poly(methyl methacrylate) spheres suspended in decalin had previously been studied as a hard sphere solution. The interparticle correlations between the spheres were found to match the Percus-Yevick closure, as had been previously seen in dynamical light scattering experiments. To expand beyond pure hard spheres, 900kDa polystyrene was added to the solution in concentrations of less than 1% by mass. The steric effects of the polystyrene were expected to produce a short-range, attractive, "sticky" potential. Experiment showed, however, that the "sticky" potential was not a stable state and that the spheres would eventually form long range aggregates.

  9. Vaccine-Drug Interactions: Cytokines, Cytochromes, and Molecular Mechanisms.

    PubMed

    Pellegrino, Paolo; Perrotta, Cristiana; Clementi, Emilio; Radice, Sonia

    2015-09-01

    Vaccinations are recommended throughout life to reduce the risk of vaccine-preventable diseases and their sequelae. Vaccines are often administered in patients with chronic diseases who are likely to be treated with several drugs. A growing number of clinical observations have indicated the possibility of interactions between vaccines and drugs, leading to changes in drug metabolism after vaccination. These interactions represent a significant concern because of the increasing use of vaccines in older patients who are likely to be treated with several drugs. Because of the possible implications of adverse reactions in terms of public health, several studies were performed to verify the risk posed by these interactions and to clarify the biologic mechanisms that drive these events. Of the several mechanisms proposed to be at the basis of vaccine-drug interactions, the most convincing evidence suggests a role of inflammatory cytokines on the regulation of specific cytochrome P450 enzymes in the liver. Differences in the cytochrome P450 enzymes involved in the metabolism of these drugs could explain these contrasting results and provide important insights to fully understand the clinical importance of these events. Further studies are required to verify whether vaccine-drug interactions may occur in other clinical settings, especially the ones for which patients are required to be vaccinated against specific diseases.

  10. Molecular force spectroscopy of homophilic nectin-1 interactions

    SciTech Connect

    Vedula, Sri Ram Krishna; Lim, T.S.; Hui Shi; Kausalya, P. Jaya; Lane, E. Birgitte; Rajagopal, Gunaretnam; Hunziker, Walter; Lim, C.T.

    2007-11-03

    Nectins are Ca{sup 2+} independent cell adhesion molecules localizing at the cadherin based adherens junctions. In this study, we have used atomic force microscopy to study interaction of a chimera of extra cellular fragment of nectin-1 and Fc of human IgG (nef-1) with wild type L-fibroblasts that express endogenous nectin-1 to elucidate the biophysical characteristics of homophilic nectin-1 trans-interactions at the level of single molecule. Bond strength distribution revealed three distinct bound states (or configurations) of trans-interactions between paired nectins, where each bound state has a unique unstressed off-rate and reactive compliance. Kinetic analysis of force-dependent off-rate of the bound state involving trans-interacting V-V domains between paired nectin-1 (unstressed off-rate {approx}1.465 {+-} 0.779 s{sup -1}, reactive compliance {approx}0.143 {+-} 0.072 nm) was found to be closest to E-cadherin, indicating that V-V domain trans-interactions are probably necessary to initiate and promote adhesions of E-cadherin at adherens junctions (AJs)

  11. How molecular interactions affect crystal morphology: the case of haloperidol.

    PubMed

    Li Destri, Giovanni; Marrazzo, Agostino; Rescifina, Antonio; Punzo, Francesco

    2011-11-01

    The tableting behaviour of drugs can be dramatically affected by changes in the crystal habit of the drug molecule. Pharmaceutical companies are therefore interested in the morphology prediction as a possible tool to optimise the industrial process. Molecular mechanics calculations embedded in dedicated software together with X-ray diffraction analysis were used to enlighten the structural properties of 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)butan-1-one-whose commercial name is haloperidol--an antipsychotic drug that contributed to the progress and revolution of psychiatric care. We defined, by means of X-ray powder diffraction, which--or how much--of the two crystallographic structures present in the Cambridge Crystallographic Database represents the commercial crystalline powder. Once the correct structure was selected, the whole structural analysis was carried out as a comparison with the already deposited structures. The available single crystal structure was used to model the X-ray powder diffraction pattern. The "real" structure was then optimised by means of molecular mechanics and the crystal morphology of the compounds was predicted with different computational methods. Analogies and differences among the different morphologies, together with the potential role of several solvents were used to try to bridge the gap between the molecular structure--that is, the atomic point of view--and the crystal habit. PMID:21656519

  12. Conserved Molecular Interactions in Centriole-to-Centrosome Conversion

    PubMed Central

    Fu, Jingyan; Lipinszki, Zoltan; Rangone, Hélène; Min, Mingwei; Mykura, Charlotte; Chao-Chu, Jennifer; Schneider, Sandra; Dzhindzhev, Nikola S.; Gottardo, Marco; Riparbelli, Maria Giovanna; Callaini, Giuliano; Glover, David M.

    2015-01-01

    Centrioles are required to assemble centrosomes for cell division and cilia for motility and signaling. New centrioles assemble perpendicularly to pre-existing ones in G1-S and elongate throughout S and G2. Fully-elongated daughter centrioles are converted into centrosomes during mitosis to be able to duplicate and organize pericentriolar material in the next cell cycle. Here we show that centriole-to-centrosome conversion requires sequential loading of Cep135, Ana1:Cep295 and Asterless:Cep152 onto daughter centrioles during mitotic progression. This generates a molecular network spanning from inner- to outer-most parts of the centriole. Ana1 forms a molecular strut within the network and its essential role can be substituted by an engineered fragment providing an alternative linkage between Asterless and Cep135. This conserved architectural framework is essential for loading Asterless:Cep152, partner of the master regulator of centriole duplication, Plk4. Our study thus uncovers the molecular basis for centriole-to-centrosome conversion that renders daughter centrioles competent for motherhood. PMID:26595382

  13. Conserved molecular interactions in centriole-to-centrosome conversion.

    PubMed

    Fu, Jingyan; Lipinszki, Zoltan; Rangone, Hélène; Min, Mingwei; Mykura, Charlotte; Chao-Chu, Jennifer; Schneider, Sandra; Dzhindzhev, Nikola S; Gottardo, Marco; Riparbelli, Maria Giovanna; Callaini, Giuliano; Glover, David M

    2016-01-01

    Centrioles are required to assemble centrosomes for cell division and cilia for motility and signalling. New centrioles assemble perpendicularly to pre-existing ones in G1-S and elongate throughout S and G2. Fully elongated daughter centrioles are converted into centrosomes during mitosis to be able to duplicate and organize pericentriolar material in the next cell cycle. Here we show that centriole-to-centrosome conversion requires sequential loading of Cep135, Ana1 (Cep295) and Asterless (Cep152) onto daughter centrioles during mitotic progression in both Drosophila melanogaster and human. This generates a molecular network spanning from the inner- to outermost parts of the centriole. Ana1 forms a molecular strut within the network, and its essential role can be substituted by an engineered fragment providing an alternative linkage between Asterless and Cep135. This conserved architectural framework is essential for loading Asterless or Cep152, the partner of the master regulator of centriole duplication, Plk4. Our study thus uncovers the molecular basis for centriole-to-centrosome conversion that renders daughter centrioles competent for motherhood.

  14. Molecular magnetic resonance imaging of brain–immune interactions

    PubMed Central

    Gauberti, Maxime; Montagne, Axel; Quenault, Aurélien; Vivien, Denis

    2014-01-01

    Although the blood–brain barrier (BBB) was thought to protect the brain from the effects of the immune system, immune cells can nevertheless migrate from the blood to the brain, either as a cause or as a consequence of central nervous system (CNS) diseases, thus contributing to their evolution and outcome. Accordingly, as the interface between the CNS and the peripheral immune system, the BBB is critical during neuroinflammatory processes. In particular, endothelial cells are involved in the brain response to systemic or local inflammatory stimuli by regulating the cellular movement between the circulation and the brain parenchyma. While neuropathological conditions differ in etiology and in the way in which the inflammatory response is mounted and resolved, cellular mechanisms of neuroinflammation are probably similar. Accordingly, neuroinflammation is a hallmark and a decisive player of many CNS diseases. Thus, molecular magnetic resonance imaging (MRI) of inflammatory processes is a central theme of research in several neurological disorders focusing on a set of molecules expressed by endothelial cells, such as adhesion molecules (VCAM-1, ICAM-1, P-selectin, E-selectin, …), which emerge as therapeutic targets and biomarkers for neurological diseases. In this review, we will present the most recent advances in the field of preclinical molecular MRI. Moreover, we will discuss the possible translation of molecular MRI to the clinical setting with a particular emphasis on myeloperoxidase imaging, autologous cell tracking, and targeted iron oxide particles (USPIO, MPIO). PMID:25505871

  15. MIiSR: Molecular Interactions in Super-Resolution Imaging Enables the Analysis of Protein Interactions, Dynamics and Formation of Multi-protein Structures.

    PubMed

    Caetano, Fabiana A; Dirk, Brennan S; Tam, Joshua H K; Cavanagh, P Craig; Goiko, Maria; Ferguson, Stephen S G; Pasternak, Stephen H; Dikeakos, Jimmy D; de Bruyn, John R; Heit, Bryan

    2015-12-01

    Our current understanding of the molecular mechanisms which regulate cellular processes such as vesicular trafficking has been enabled by conventional biochemical and microscopy techniques. However, these methods often obscure the heterogeneity of the cellular environment, thus precluding a quantitative assessment of the molecular interactions regulating these processes. Herein, we present Molecular Interactions in Super Resolution (MIiSR) software which provides quantitative analysis tools for use with super-resolution images. MIiSR combines multiple tools for analyzing intermolecular interactions, molecular clustering and image segmentation. These tools enable quantification, in the native environment of the cell, of molecular interactions and the formation of higher-order molecular complexes. The capabilities and limitations of these analytical tools are demonstrated using both modeled data and examples derived from the vesicular trafficking system, thereby providing an established and validated experimental workflow capable of quantitatively assessing molecular interactions and molecular complex formation within the heterogeneous environment of the cell.

  16. MIiSR: Molecular Interactions in Super-Resolution Imaging Enables the Analysis of Protein Interactions, Dynamics and Formation of Multi-protein Structures

    PubMed Central

    Caetano, Fabiana A.; Dirk, Brennan S.; Tam, Joshua H. K.; Cavanagh, P. Craig; Goiko, Maria; Ferguson, Stephen S. G.; Pasternak, Stephen H.; Dikeakos, Jimmy D.; de Bruyn, John R.; Heit, Bryan

    2015-01-01

    Our current understanding of the molecular mechanisms which regulate cellular processes such as vesicular trafficking has been enabled by conventional biochemical and microscopy techniques. However, these methods often obscure the heterogeneity of the cellular environment, thus precluding a quantitative assessment of the molecular interactions regulating these processes. Herein, we present Molecular Interactions in Super Resolution (MIiSR) software which provides quantitative analysis tools for use with super-resolution images. MIiSR combines multiple tools for analyzing intermolecular interactions, molecular clustering and image segmentation. These tools enable quantification, in the native environment of the cell, of molecular interactions and the formation of higher-order molecular complexes. The capabilities and limitations of these analytical tools are demonstrated using both modeled data and examples derived from the vesicular trafficking system, thereby providing an established and validated experimental workflow capable of quantitatively assessing molecular interactions and molecular complex formation within the heterogeneous environment of the cell. PMID:26657340

  17. Conformational Changes in Acetylcholine Binding Protein Investigated by Temperature Accelerated Molecular Dynamics

    PubMed Central

    Mohammad Hosseini Naveh, Zeynab; Malliavin, Therese E.; Maragliano, Luca; Cottone, Grazia; Ciccotti, Giovanni

    2014-01-01

    Despite the large number of studies available on nicotinic acetylcholine receptors, a complete account of the mechanistic aspects of their gating transition in response to ligand binding still remains elusive. As a first step toward dissecting the transition mechanism by accelerated sampling techniques, we study the ligand-induced conformational changes of the acetylcholine binding protein (AChBP), a widely accepted model for the full receptor extracellular domain. Using unbiased Molecular Dynamics (MD) and Temperature Accelerated Molecular Dynamics (TAMD) simulations we investigate the AChBP transition between the apo and the agonist-bound state. In long standard MD simulations, both conformations of the native protein are stable, while the agonist-bound structure evolves toward the apo one if the orientation of few key sidechains in the orthosteric cavity is modified. Conversely, TAMD simulations initiated from the native conformations are able to produce the spontaneous transition. With respect to the modified conformations, TAMD accelerates the transition by at least a factor 10. The analysis of some specific residue-residue interactions points out that the transition mechanism is based on the disruption/formation of few key hydrogen bonds. Finally, while early events of ligand dissociation are observed already in standard MD, TAMD accelerates the ligand detachment and, at the highest TAMD effective temperature, it is able to produce a complete dissociation path in one AChBP subunit. PMID:24551117

  18. The Interactive Minority Game: a Web-based investigation of human market interactions

    NASA Astrophysics Data System (ADS)

    Laureti, Paolo; Ruch, Peter; Wakeling, Joseph; Zhang, Yi-Cheng

    2004-01-01

    The unprecedented access offered by the World Wide Web brings with it the potential to gather huge amounts of data on human activities. Here we exploit this by using a toy model of financial markets, the Minority Game (MG), to investigate human speculative trading behaviour and information capacity. Hundreds of individuals have played a total of tens of thousands of game turns against computer-controlled agents in the Web-based Interactive Minority Game. The analytical understanding of the MG permits fine-tuning of the market situations encountered, allowing for investigation of human behaviour in a variety of controlled environments. In particular, our results indicate a transition in players’ decision-making, as the markets become more difficult, between deductive behaviour making use of short-term trends in the market, and highly repetitive behaviour that ignores entirely the market history, yet outperforms random decision-making.

  19. The molecular mechanism for interaction of ceruloplasmin and myeloperoxidase

    NASA Astrophysics Data System (ADS)

    Bakhautdin, Bakytzhan; Bakhautdin, Esen Göksöy

    2016-04-01

    Ceruloplasmin (Cp) is a copper-containing ferroxidase with potent antioxidant activity. Cp is expressed by hepatocytes and activated macrophages and has been known as physiologic inhibitor of myeloperoxidase (MPO). Enzymatic activity of MPO produces anti-microbial agents and strong prooxidants such as hypochlorous acid and has a potential to damage host tissue at the sites of inflammation and infection. Thus Cp-MPO interaction and inhibition of MPO has previously been suggested as an important control mechanism of excessive MPO activity. Our aim in this study was to identify minimal Cp domain or peptide that interacts with MPO. We first confirmed Cp-MPO interaction by ELISA and surface plasmon resonance (SPR). SPR analysis of the interaction yielded 30 nM affinity between Cp and MPO. We then designed and synthesized 87 overlapping peptides spanning the entire amino acid sequence of Cp. Each of the peptides was tested whether it binds to MPO by direct binding ELISA. Two of the 87 peptides, P18 and P76 strongly interacted with MPO. Amino acid sequence analysis of identified peptides revealed high sequence and structural homology between them. Further structural analysis of Cp's crystal structure by PyMOL software unfolded that both peptides represent surface-exposed sites of Cp and face nearly the same direction. To confirm our finding we raised anti-P18 antisera in rabbit and demonstrated that this antisera disrupts Cp-MPO binding and rescues MPO activity. Collectively, our results confirm Cp-MPO interaction and identify two nearly identical sites on Cp that specifically bind MPO. We propose that inhibition of MPO by Cp requires two nearly identical sites on Cp to bind homodimeric MPO simultaneously and at an angle of at least 120 degrees, which, in turn, exerts tension on MPO and results in conformational change.

  20. Polymer brushes with nanoinclusions under shear: A molecular dynamics investigation

    PubMed Central

    Milchev, A.; Dimitrov, D. I.; Binder, K.

    2010-01-01

    We use molecular dynamics simulations with a dissipative particle dynamics thermostat to study the behavior of nanosized inclusions (colloids) in a polymer brush under shear whereby the solvent is explicitly included in the simulation. The brush is described by a bead-spring model for flexible polymer chains, grafted on a solid substrate, while the polymer-soluble nanoparticles in the solution are taken as soft spheres whose diameter is about three times larger than that of the chain segments and the solvent. We find that the brush number density profile, as well as the density profiles of the nanoinclusions and the solvent, remains insensitive to strong shear although the grafted chains tilt in direction of the flow. The thickness of the penetration layer of nanoinclusions, as well as their average concentration in the brush, stays largely unaffected even at the strongest shear. Our result manifests the remarkable robustness of polymer brushes with embedded nanoparticles under high shear which could be of importance for technological applications. PMID:21045924

  1. Probing - and - Molecular Interactions via Irmpd Experiments and Computational Chemistry

    NASA Astrophysics Data System (ADS)

    Hopkins, Scott; McMahon, Terry

    2015-06-01

    Experiments carried out at the CLIO Free Electron Facility have been used to probe a range of novel bonding motifs and dissociation dynamics in a variety of chemical systems. Among these are species which exhibit anion-pi interactions in complexes of halide ions with aromatic ring systems with electron withdrawing substituents; charge solvated and zwitterionic clusters of protonated methylamines with phenylalanines; hydrogen bonded dimers of nucleic acid analogues and Pd complexes potentially involving agnostic hydrogen bond interactions. Accompanying DFT computational work is used to assist in identifying the most probable structure(s) present in the IRMPD experiments.

  2. Protein Interaction Data Curation - The International Molecular Exchange Consortium (IMEx)

    PubMed Central

    Orchard, Sandra; Kerrien, Samuel; Abbani, Sara; Aranda, Bruno; Bhate, Jignesh; Bidwell, Shelby; Bridge, Alan; Briganti, Leonardo; Brinkman, Fiona S. L.; Cesareni, Gianni; Chatr-aryamontri, Andrew; Chautard, Emilie; Chen, Carol; Dumousseau, Marine; Goll, Johannes; Hancock, Robert E. W.; Hannick, Linda I.; Jurisica, Igor; Khadake, Jyoti; Lynn, David J.; Mahadevan, Usha; Perfetto, Livia; Raghunath, Arathi; Ricard-Blum, Sylvie; Roechert, Bernd; Salwinski, Lukasz; Stümpflen, Volker; Tyers, Mike; Uetz, Peter; Xenarios, Ioannis; Hermjakob, Henning

    2013-01-01

    The IMEx consortium is an international collaboration between major public interaction data providers to share curation effort and make a non-redundant set of protein interactions available in a single search interface on a common website (www.imexconsortium.org). Common curation rules have been developed and a central registry is used to manage the selection of articles to enter into the dataset. The advantages of such a service to the user, quality control measures adopted and data distribution practices are discussed. PMID:22453911

  3. Guest:host interactions of lidocaine and prilocaine with natural cyclodextrins: Spectral and molecular modeling studies

    NASA Astrophysics Data System (ADS)

    Rajendiran, N.; Mohandoss, T.; Saravanan, J.

    2014-11-01

    Inclusion complex formation of two local anesthetics drugs (lidocaine (LC) and prilocaine (PC)) with α- and β-cyclodextrins (CDs) in aqueous solution were studied by absorption, fluorescence, time-resolved fluorescence and molecular modeling methods. The formation of inclusion complexes was confirmed by 1H NMR, FTIR, differential scanning calorimetry, SEM, TEM and X-ray diffractometry. Both drugs formed 1:1 inclusion complex and exhibit biexponential decay in water whereas triexponential decay in the CD solution. Nanosized self-aggregated particles of drug: CD complexes were found by TEM. Both experimental and theoretical studies revealed that the phenyl ring with the amide group of the drug is encapsulated in the hydrophobic CD nanocavity. Investigations of energetic and thermodynamic properties confirmed the stability of the inclusion complexes. van der Waals interactions are mainly responsible for enthalpy driven complex formation of LC and PC with CDs.

  4. Guest:host interactions of lidocaine and prilocaine with natural cyclodextrins: spectral and molecular modeling studies.

    PubMed

    Rajendiran, N; Mohandoss, T; Saravanan, J

    2014-11-11

    Inclusion complex formation of two local anesthetics drugs (lidocaine (LC) and prilocaine (PC)) with α- and β-cyclodextrins (CDs) in aqueous solution were studied by absorption, fluorescence, time-resolved fluorescence and molecular modeling methods. The formation of inclusion complexes was confirmed by 1H NMR, FTIR, differential scanning calorimetry, SEM, TEM and X-ray diffractometry. Both drugs formed 1:1 inclusion complex and exhibit biexponential decay in water whereas triexponential decay in the CD solution. Nanosized self-aggregated particles of drug: CD complexes were found by TEM. Both experimental and theoretical studies revealed that the phenyl ring with the amide group of the drug is encapsulated in the hydrophobic CD nanocavity. Investigations of energetic and thermodynamic properties confirmed the stability of the inclusion complexes. van der Waals interactions are mainly responsible for enthalpy driven complex formation of LC and PC with CDs.

  5. Binding interaction of atorvastatin with bovine serum albumin: Spectroscopic methods and molecular docking

    NASA Astrophysics Data System (ADS)

    Wang, Qi; Huang, Chuan-ren; Jiang, Min; Zhu, Ying-yao; Wang, Jing; Chen, Jun; Shi, Jie-hua

    2016-03-01

    The interaction of atorvastatin with bovine serum albumin (BSA) was investigated using multi-spectroscopic methods and molecular docking technique for providing important insight into further elucidating the store and transport process of atorvastatin in the body and the mechanism of action and pharmacokinetics. The experimental results revealed that the fluorescence quenching mechanism of BSA induced atorvastatin was a combined dynamic and static quenching. The binding constant and number of binding site of atorvastatin with BSA under simulated physiological conditions (pH = 7.4) were 1.41 × 105 M- 1 and about 1 at 310 K, respectively. The values of the enthalpic change (ΔH0), entropic change (ΔS0) and Gibbs free energy (ΔG0) in the binding process of atorvastatin with BSA at 310 K were negative, suggesting that the binding process of atorvastatin and BSA was spontaneous and the main interaction forces were van der Waals force and hydrogen bonding interaction. Moreover, atorvastatin was bound into the subdomain IIA (site I) of BSA, resulting in a slight change of the conformation of BSA.

  6. Virus and host genomic, molecular, and cellular interactions during Marek's disease pathogenesis and oncogenesis.

    PubMed

    McPherson, M C; Delany, M E

    2016-02-01

    Marek's Disease Virus (MDV) is a chicken alphaherpesvirus that causes paralysis, chronic wasting, blindness, and fatal lymphoma development in infected, susceptible host birds. This disease and its protective vaccines are highly relevant research targets, given their enormous impact within the poultry industry. Further, Marek's disease (MD) serves as a valuable model for the investigation of oncogenic viruses and herpesvirus patterns of viral latency and persistence--as pertinent to human health as to poultry health. The objectives of this article are to review MDV interactions with its host from a variety of genomic, molecular, and cellular perspectives. In particular, we focus on cytogenetic studies, which precisely assess the physical status of the MDV genome in the context of the chicken host genome. Combined, the cytogenetic and genomic research indicates that MDV-host genome interactions, specifically integration of the virus into the host telomeres, is a key feature of the virus life cycle, contributing to the viral achievement of latency, transformation, and reactivation of lytic replication. We present a model that outlines the variety of virus-host interactions, at the multiple levels, and with regard to the disease states. PMID:26755654

  7. Virus and host genomic, molecular, and cellular interactions during Marek's disease pathogenesis and oncogenesis

    PubMed Central

    McPherson, M. C.; Delany, M. E.

    2016-01-01

    Marek's Disease Virus (MDV) is a chicken alphaherpesvirus that causes paralysis, chronic wasting, blindness, and fatal lymphoma development in infected, susceptible host birds. This disease and its protective vaccines are highly relevant research targets, given their enormous impact within the poultry industry. Further, Marek's disease (MD) serves as a valuable model for the investigation of oncogenic viruses and herpesvirus patterns of viral latency and persistence—as pertinent to human health as to poultry health. The objectives of this article are to review MDV interactions with its host from a variety of genomic, molecular, and cellular perspectives. In particular, we focus on cytogenetic studies, which precisely assess the physical status of the MDV genome in the context of the chicken host genome. Combined, the cytogenetic and genomic research indicates that MDV-host genome interactions, specifically integration of the virus into the host telomeres, is a key feature of the virus life cycle, contributing to the viral achievement of latency, transformation, and reactivation of lytic replication. We present a model that outlines the variety of virus-host interactions, at the multiple levels, and with regard to the disease states. PMID:26755654

  8. Lysozyme-magnesium aluminum silicate microparticles: Molecular interaction, bioactivity and release studies.

    PubMed

    Kanjanakawinkul, Watchara; Medlicott, Natalie J; Rades, Thomas; Puttipipatkhachorn, Satit; Pongjanyakul, Thaned

    2015-09-01

    The objectives of this study were to investigate the adsorption behavior of lysozyme (LSZ) onto magnesium aluminum silicate (MAS) at various pHs and to characterize the LSZ-MAS microparticles obtained from the molecular interaction between LSZ and MAS. The results showed that LSZ could be bound onto the MAS layers at different pHs, leading to the formation of LSZ-MAS microparticles. The higher preparation pH permitted greater adsorption affinity but a lower adsorption capacity of LSZ onto MAS. LSZ could interact with MAS via hydrogen bonds and electrostatic forces, resulting in the formation of intercalated nanocomposites. The particle size, %LSZ adsorbed, and LSZ release rate of LSZ-MAS microparticles increased when the LSZ-MAS ratio was increased. The secondary structure of LSZ bound onto the MAS layers in microparticles prepared at various pHs was altered compared with that of native LSZ. Moreover, the LSZ extracted from microparticles prepared at pH 4 showed an obvious change in the tertiary structure, leading to a decrease in the biological activity of the LSZ released. These findings suggested that LSZ can strongly interact with MAS to form microparticles that may potentially be used as delivery systems for sustained protein release. PMID:26193680

  9. Protein-Carbohydrate Interactions Studied by NMR: From Molecular Recognition to Drug Design

    PubMed Central

    Fernández-Alonso, María del Carmen; Díaz, Dolores; Berbis, Manuel Álvaro; Marcelo, Filipa; Cañada, Javier; Jiménez-Barbero, Jesús

    2012-01-01

    Diseases that result from infection are, in general, a consequence of specific interactions between a pathogenic organism and the cells. The study of host-pathogen interactions has provided insights for the design of drugs with therapeutic properties. One area that has proved to be promising for such studies is the constituted by carbohydrates which participate in biological processes of paramount importance. On the one hand, carbohydrates have shown to be information carriers with similar, if not higher, importance than traditionally considered carriers as amino acids and nucleic acids. On the other hand, the knowledge on molecular recognition of sugars by lectins and other carbohydrate-binding proteins has been employed for the development of new biomedical strategies. Biophysical techniques such as X-Ray crystallography and NMR spectroscopy lead currently the investigation on this field. In this review, a description of traditional and novel NMR methodologies employed in the study of sugar-protein interactions is briefly presented in combination with a palette of NMR-based studies related to biologically and/or pharmaceutically relevant applications. PMID:23305367

  10. Molecular Dynamics Simulation of Shock Waves Interacting with Nano-structures

    NASA Astrophysics Data System (ADS)

    Alqananwah, Ahmad; Koplik, Joel; Andreopoulos, Yiannis

    2009-11-01

    Typical theoretical treatments of shock wave interactions are based on a continuum approach, which cannot resolve the spatial variations in solids with nano-scale porous structure. To investigate such interactions we have developed a molecular dynamics simulation model, based on Lennard-Jones interactions. A piston, modeled as a uni-directional repulsive force field translating at a prescribed velocity, impinges on a region of gas which is compressed to form a shock, which in turn is driven against an atomistic solid wall. Periodic boundary conditions are used in the directions orthogonal to the piston motion, and we have considered solids based on either atoms tethered to lattice sites by stiff springs, or on embedded atom potentials. Velocity, temperature and stress fields are computed locally in both gas and solid regions, and displacements within the solid are interpreted in terms of its elastic constants. In this talk we present preliminary results, and the longer-term goal of this work is to understand energy transport and absorption in porous materials.

  11. Binding interaction of atorvastatin with bovine serum albumin: Spectroscopic methods and molecular docking.

    PubMed

    Wang, Qi; Huang, Chuan-ren; Jiang, Min; Zhu, Ying-yao; Wang, Jing; Chen, Jun; Shi, Jie-hua

    2016-03-01

    The interaction of atorvastatin with bovine serum albumin (BSA) was investigated using multi-spectroscopic methods and molecular docking technique for providing important insight into further elucidating the store and transport process of atorvastatin in the body and the mechanism of action and pharmacokinetics. The experimental results revealed that the fluorescence quenching mechanism of BSA induced atorvastatin was a combined dynamic and static quenching. The binding constant and number of binding site of atorvastatin with BSA under simulated physiological conditions (pH=7.4) were 1.41 × 10(5) M(-1) and about 1 at 310K, respectively. The values of the enthalpic change (ΔH(0)), entropic change (ΔS(0)) and Gibbs free energy (ΔG(0)) in the binding process of atorvastatin with BSA at 310K were negative, suggesting that the binding process of atorvastatin and BSA was spontaneous and the main interaction forces were van der Waals force and hydrogen bonding interaction. Moreover, atorvastatin was bound into the subdomain IIA (site I) of BSA, resulting in a slight change of the conformation of BSA. PMID:26688207

  12. Molecular interactions in reverse hexagonal mesophase in the presence of Cyclosporin A.

    PubMed

    Libster, Dima; Ishai, Paul Ben; Aserin, Abraham; Shoham, Gil; Garti, Nissim

    2009-02-01

    The present work investigates the detailed molecular structure of the H(II) mesophase of GMO/tricaprylin/phosphatidylcholine/water system in the presence of hydrophobic model peptide Cyclosporin A (CSA) via ATR-FTIR analysis. The conformation of the peptide in the hexagonal mesophase, as well as its location and specific interactions with the components of the carrier, were studied. Incorporation of phosphatidylcholine to the ternary GMO/tricaprylin/water system caused competition for water binding between the hydroxyl groups of GMO and the phosphate groups of the phosphatidylcholine (PC) leading to dehydration of the GMO hydroxyls in favor of phospholipid hydration. Analysis of CSA solubilization effect on the H(II) mesophase revealed a significant increase in the strength of hydrogen bonding with surfactant hydrogen-bonded carbonyls, indicating interaction of the peptide with the CO groups of the surfactants. The peptide probably caused partial replacement of the intramolecular hydrogen bonds of the mesophase carbonyl groups with intermolecular hydrogen bonds of these carbonyl groups with the peptide. Furthermore, analysis of the Amide I' peak in the FTIR spectra of the peptide demonstrated that two pairs of its internal hydrogen bonds are disrupted when it is incorporated. The partial disruption of the internal hydrogen bonds seems to cause an outward rotation of the peptide amide groups involved, resulting in more efficient intermolecular hydrogen-bonding ability. Apparently, this conformational change increased the hydrophilic properties of CSA, even making it susceptible to a weak interaction with the GMO hydroxyl groups in the interfacial region.

  13. Real-time investigation of nucleic acids phosphorylation process using molecular beacons.

    PubMed

    Tang, Zhiwen; Wang, Kemin; Tan, Weihong; Ma, Changbei; Li, Jun; Liu, Lingfeng; Guo, Qiuping; Meng, Xiangxian

    2005-01-01

    Phosphorylation of nucleic acids is an indispensable process to repair strand interruption of nucleic acids. We have studied the process of phosphorylation using molecular beacon (MB) DNA probes in real-time and with high selectivity. The MB employed in this method is devised to sense the product of a 'phosphorylation-ligation' coupled enzyme reaction. Compared with the current assays, this novel method is convenient, fast, selective, highly sensitive and capable of real-time monitoring in a homogenous solution. The preference of T4 polynucleotide kinase (T4 PNK) has been investigated using this approach. The results revealed that a single-stranded oligonucleotide containing guanine at the 5' termini is most preferred, while those utilizing cytosine in this location are least preferred. The preference of (T)9 was reduced greatly when phosphoryl was modified at the 5' end, implying that T4 PNK could discern the phosphorylated/unphosphorylated oligonucleotides. The increase of oligonucleotide DNA length leads to an enhancement in preference. A fast and accurate method for assaying the kinase activity of T4 PNK has been developed with a wide linear detection range from 0.002 to 4.0 U/ml in 3 min. The effects of certain factors, such as NTP, ADP, (NH4)2SO4 and Na2HPO4, on phosphorylation have been investigated. This novel approach enables us to investigate the interactions between proteins and nucleic acids in a homogenous solution, such as those found in DNA repair or in drug development.

  14. Investigation of protein conformation and interactions with salts via X-ray absorption spectroscopy

    PubMed Central

    Schwartz, Craig P.; Uejio, Janel S.; Duffin, Andrew M.; England, Alice H.; Kelly, Daniel N.; Prendergast, David; Saykally, Richard J.

    2010-01-01

    Nitrogen K-edge spectra of aqueous triglycine were measured using liquid microjets, and the effects of Hofmeister-active salts on the spectra were observed. Spectra simulated using density functional theory, sampled from room temperature classical molecular dynamics trajectories, capture all major features in the measured spectra. The spectrum of triglycine in water is quite similar to that in the presence of chaotropic sodium bromide (and other halides), which raises the solubility of proteins. However, a new feature is found when kosmotropic Na2SO3, which lowers solubility, is present; this feature results from excitations of the nitrogen atom in the terminal amino group of triglycine. Both direct interactions between this salt and the protonated amino terminus, as well as corresponding changes in the conformational dynamics of the system, contribute to this new feature. These molecular measurements support a different mechanism for the Hofmeister effect than has previously been suggested based on thermodynamic measurements. It is also shown that near edge X-ray absorption fine structure (NEXAFS) is sensitive to strong direct interaction between certain salts and charged peptides. However, by investigating the sensitivity of NEXAFS to the extreme structural differences between model β-sheets and α-helices, we conclude that this technique is relatively insensitive to secondary structure of peptides and proteins. PMID:20660784

  15. Copromicroscopic and molecular investigations on intestinal parasites in kenneled dogs.

    PubMed

    Simonato, Giulia; Frangipane di Regalbono, Antonio; Cassini, Rudi; Traversa, Donato; Beraldo, Paola; Tessarin, Cinzia; Pietrobelli, Mario

    2015-05-01

    Intestinal parasites are common in dogs worldwide, and their importance has recently increased for a renewed awareness on the public health relevance that some of them have. In this study, the prevalence of helminths and protozoa was evaluated by microscopy in 318 canine faecal samples collected from eight rescue shelters in the North-eastern Italy; 285 of them were also submitted to the molecular characterization of Giardia duodenalis and Cryptosporidium spp. isolates. An analysis was performed to evaluate the prevalence rates in relation to canine individual data, shelter provenance and anthelmintic treatments. Overall, 52.5% (167/318) of faecal samples were positive for at least one parasite. Trichuris vulpis showed the highest overall prevalence rate (29.2%), followed by G. duodenalis (15.1%), Toxocara canis (9.7%), ancylostomatids (8.2%) and Cystoisospora (5.7%). The prevalence of G. duodenalis, evaluated by real-time PCR, was 57.9% (165/285), and 79 isolates were characterized by nested PCR on the β-giardin gene. The assemblages found were mainly the host-specific genotypes C and D, while only one assemblage was identified as the human-specific genotype B1. Isolates of Cryptosporidium spp., recorded in 3/285 (1.1%) stool samples, were Cryptosporidium parvum based on the characterization of the Cryptosporidium oocyst wall protein (COWP) gene. Although the results describe a relatively limited risk of dog-originating zoonoses, there is the need to improve the quality of shelter practices towards better health managements for safe pet-adoption campaigns and a minimization of the environmental faecal pollution with canine intestinal parasites. PMID:25687526

  16. Calsyntenin-3 molecular architecture and interaction with neurexin 1α.

    PubMed

    Lu, Zhuoyang; Wang, Yun; Chen, Fang; Tong, Huimin; Reddy, M V V V Sekhar; Luo, Lin; Seshadrinathan, Suchithra; Zhang, Lei; Holthauzen, Luis Marcelo F; Craig, Ann Marie; Ren, Gang; Rudenko, Gabby

    2014-12-12

    Calsyntenin 3 (Cstn3 or Clstn3), a recently identified synaptic organizer, promotes the development of synapses. Cstn3 localizes to the postsynaptic membrane and triggers presynaptic differentiation. Calsyntenin members play an evolutionarily conserved role in memory and learning. Cstn3 was recently shown in cell-based assays to interact with neurexin 1α (n1α), a synaptic organizer that is implicated in neuropsychiatric disease. Interaction would permit Cstn3 and n1α to form a trans-synaptic complex and promote synaptic differentiation. However, it is contentious whether Cstn3 binds n1α directly. To understand the structure and function of Cstn3, we determined its architecture by electron microscopy and delineated the interaction between Cstn3 and n1α biochemically and biophysically. We show that Cstn3 ectodomains form monomers as well as tetramers that are stabilized by disulfide bonds and Ca(2+), and both are probably flexible in solution. We show further that the extracellular domains of Cstn3 and n1α interact directly and that both Cstn3 monomers and tetramers bind n1α with nanomolar affinity. The interaction is promoted by Ca(2+) and requires minimally the LNS domain of Cstn3. Furthermore, Cstn3 uses a fundamentally different mechanism to bind n1α compared with other neurexin partners, such as the synaptic organizer neuroligin 2, because Cstn3 does not strictly require the sixth LNS domain of n1α. Our structural data suggest how Cstn3 as a synaptic organizer on the postsynaptic membrane, particularly in tetrameric form, may assemble radially symmetric trans-synaptic bridges with the presynaptic synaptic organizer n1α to recruit and spatially organize proteins into networks essential for synaptic function.

  17. Molecular dynamics, spin dynamics study of phonon-magnon interactions in BCC iron

    NASA Astrophysics Data System (ADS)

    Perera, Dilina; Landau, David P.; Stocks, G. Malcolm; Nicholson, Don; Eisenbach, Markus; Yin, Junqi

    2013-03-01

    By combining an atomistic many-body potential (Finnis-Sinclair) with a classical Heisenberg-like spin Hamiltonian, we perform combined molecular and spin dynamics simulations to investigate phonon-magnon interactions in BCC iron. The coupling between atomic and spin degrees of freedom is established via a distance dependent exchange interaction derived from first principles electronic structure calculations. Coupled equations of motion are integrated using a second order Suzuki-Trotter decomposition of the exponential time evolution operator. To investigate the effect of lattice vibrations on spin wave spectrum, we calculate spin-spin and density-density dynamic structure factors S(q, ω), and compare that to the results obtained from pure spin dynamics simulations performed on a rigid lattice. In the presence of lattice vibrations, we observe an additional peak in the longitudinal spin-spin dynamic structure factor which coincides with the peak position in density-density dynanmic structure factor. Research sponsored by the U.S. Department of Energy, Office of Basic Energy Sciences, Materials Sciences and Engineering Division, ''Center for Defect Physics,'' an Energy Frontier Research Center

  18. Analytic nuclear forces and molecular properties from full configuration interaction quantum Monte Carlo

    SciTech Connect

    Thomas, Robert E.; Overy, Catherine; Opalka, Daniel; Alavi, Ali; Knowles, Peter J.; Booth, George H.

    2015-08-07

    Unbiased stochastic sampling of the one- and two-body reduced density matrices is achieved in full configuration interaction quantum Monte Carlo with the introduction of a second, “replica” ensemble of walkers, whose population evolves in imaginary time independently from the first and which entails only modest additional computational overheads. The matrices obtained from this approach are shown to be representative of full configuration-interaction quality and hence provide a realistic opportunity to achieve high-quality results for a range of properties whose operators do not necessarily commute with the Hamiltonian. A density-matrix formulated quasi-variational energy estimator having been already proposed and investigated, the present work extends the scope of the theory to take in studies of analytic nuclear forces, molecular dipole moments, and polarisabilities, with extensive comparison to exact results where possible. These new results confirm the suitability of the sampling technique and, where sufficiently large basis sets are available, achieve close agreement with experimental values, expanding the scope of the method to new areas of investigation.

  19. Molecular analyses of nuclear-cytoplasmic interactions affecting plant growth and yield. Final technical report

    SciTech Connect

    Newton, K.J.

    1998-11-01

    Mitochondria have a central role in the production of cellular energy. The biogenesis and functioning of mitochondria depends on the expression of both mitochondrial and nuclear genes. One approach to investigating the role of nuclear-mitochondrial cooperation in plant growth and development is to identify combinations of nuclear and mitochondrial genomes that result in altered but sublethal phenotypes. Plants that have certain maize nuclear genotypes in combination with cytoplasmic genomes from more distantly-related teosintes can exhibit incompatible phenotypes, such as reduced plant growth and yield and cytoplasmic male sterility, as well as altered mitochondrial gene expression. The characterization of these nuclear-cytoplasmic interactions was the focus of this grant. The authors were investigating the effects of two maize nuclear genes, RcmI and Mct, on mitochondrial function and gene expression. Plants with the teosinte cytoplasms and homozygous for the recessive rcm allele are small (miniature) and-slow-growing and the kernels are reduced in size. The authors mapped this locus to molecular markers on chromosome 7 and attempted to clone this locus by transposon tagging. The effects of the nuclear-cytoplasmic interaction on mitochondrial function and mitochondrial protein profiles were also studied.

  20. Detecting differential patterns of interaction in molecular pathways

    PubMed Central

    Yajima, Masanao; Telesca, Donatello; Ji, Yuan; Müller, Peter

    2015-01-01

    We consider statistical inference for potentially heterogeneous patterns of association characterizing the expression of bio-molecular pathways across different biologic conditions. We discuss a modeling approach based on Gaussian-directed acyclic graphs and provide computational and methodological details needed for posterior inference. Our application finds motivation in reverse phase protein array data from a study on acute myeloid leukemia, where interest centers on contrasting refractory versus relapsed patients. We illustrate the proposed method through both synthetic and case study data. PMID:25519431

  1. An Investigation into the Sex-Race-Ability Interaction.

    ERIC Educational Resources Information Center

    Strauch, Barry

    In a recent article Jensen proposed the existence of what was termed the sex x race x ability interaction in which the differences in mental ability between the black sexes were larger than the corresponding differences among whites. Three large sources of data that were analyzed failed to reveal the interaction. Since Jensen's own work suggested…

  2. Investigating the Communicative Outcomes of Task-Based Interaction.

    ERIC Educational Resources Information Center

    Yule, George; Powers, Maggie

    1994-01-01

    Studied communicative outcomes of nonnative speaker interactions and presents a methodological framework for the analysis of different solutions to referential problems encountered in a task. The framework permits identification of what types of participation arrangements might result in more or less beneficial interactions for learners. (Contains…

  3. An Interactive Graphics Program for Investigating Digital Signal Processing.

    ERIC Educational Resources Information Center

    Miller, Billy K.; And Others

    1983-01-01

    Describes development of an interactive computer graphics program for use in teaching digital signal processing. The program allows students to interactively configure digital systems on a monitor display and observe their system's performance by means of digital plots on the system's outputs. A sample program run is included. (JN)

  4. The interaction of T-Tauri stars with molecular clouds

    NASA Technical Reports Server (NTRS)

    Silk, J.; Norman, C.

    1980-01-01

    Winds from T-Tauri stars may provide an important dynamical input into cold molecular clouds. If the frequency of T-Tauri stars exceeds 20/cu pc, wind-driven shells collide and form ram-pressure-confined clumps. The supersonic clump motions can account for cloud line widths. Clumps collide inelastically, coalescing and eventually becoming Jeans unstable. For characteristic dark cloud temperatures low-mass stars form, and it is speculated that in this manner clouds can be self-sustaining for 10 million to 100 million yr. Only when either the gas supply is exhausted or an external trigger stimulates massive star formation (for example, by heating the cloud or enhancing the clump collision rate), will the cloud eventually be disrupted. A natural consequence of this model is that dark cloud lifetimes are identified with the duration of low-mass star formation, inferred to exceed 10 million yr from studies of nearby star clusters. Other implications include the prediction of the existence of embedded low-mass stars in turbulent cloud cores, the presence of an internal source of radiation in dark clouds, and a clumpy structure for cold molecular clouds.

  5. A QTAIM and stress tensor investigation of the torsion path of a light-driven fluorene molecular rotary motor.

    PubMed

    Hu, Ming Xing; Xu, Tianlv; Momen, Roya; Huan, Guo; Kirk, Steven R; Jenkins, Samantha; Filatov, Michael

    2016-11-01

    The utility of the QTAIM/stress tensor analysis method for characterizing the photoisomerization of light driven molecular rotary machines is investigated on the example of the torsion path in fluorene molecular motor. The scalar and vector descriptors of QTAIM/stress tensor reveal additional information on the bonding interactions between the rotating units of the motor, which cannot be obtained from the analysis of the ground and excited state potential energy surfaces. The topological features of the fluorene motor molecular graph display that, upon the photoexcitation a certain increase in the torsional stiffness of the rotating bond can be attributed to the increasing topological stability of the rotor carbon atom attached to the rotation axle. The established variations in the torsional stiffness of the rotating bond may cause transfer of certain fraction of the torsional energy to other internal degrees of freedom, such as the pyramidalization distortion. © 2016 Wiley Periodicals, Inc. PMID:27671359

  6. Molecular Dynamic Simulations of Interaction of an AFM Probe with the Surface of an SCN Sample

    NASA Technical Reports Server (NTRS)

    Bune, Adris; Kaukler, William; Rose, M. Franklin (Technical Monitor)

    2001-01-01

    Molecular dynamic (MD) simulations is conducted in order to estimate forces of probe-substrate interaction in the Atomic Force Microscope (AFM). First a review of available molecular dynamic techniques is given. Implementation of MD simulation is based on an object-oriented code developed at the University of Delft. Modeling of the sample material - succinonitrile (SCN) - is based on the Lennard-Jones potentials. For the polystyrene probe an atomic interaction potential is used. Due to object-oriented structure of the code modification of an atomic interaction potential is straight forward. Calculation of melting temperature is used for validation of the code and of the interaction potentials. Various fitting parameters of the probe-substrate interaction potentials are considered, as potentials fitted to certain properties and temperature ranges may not be reliable for the others. This research provides theoretical foundation for an interpretation of actual measurements of an interaction forces using AFM.

  7. Molecular interactions between caffeine and catechins in green tea.

    PubMed

    Colon, Marta; Nerin, Cristina

    2014-07-16

    Migration of green tea components from an active packaging material containing green tea extract was performed in water and 3% acetic acid in water. The migration values for acid simulant were much higher than the values obtained in water. The influence of the acidic media in solutions of catechin standards and green tea extract was evaluated by liquid chromatography. Catechin, epicatechin, and caffeine from the green tea extract exhibited major variation in their concentrations values, with increases of 29.90, 20.75, and 15.95%, respectively, in acidic medium. The results suggested that catechins and caffeine form complexes through intermolecular interactions in neutral media and that these interactions are broken in acidic media. The continuous variation method was also performed to confirm the stoichiometry of the complexes between catechins and caffeine. Finally, a computer simulation was applied by Chem Pro 12.0, and the energies involved were calculated to confirm the experimental results obtained.

  8. Crowding in extremophiles: linkage between solvation and weak protein-protein interactions, stability and dynamics, provides insight into molecular adaptation.

    PubMed

    Ebel, Christine; Zaccai, Giuseppe

    2004-01-01

    The study of the molecular adaptation of microorganisms to extreme environments (solvent, temperature, etc.) has provided tools to investigate the complex relationships between protein-solvent and protein-protein interactions, protein stability and protein dynamics, and how they are modulated by the crowded environment of the cell. We have evaluated protein-solvent and protein-protein interactions by solution experiments (analytical ultracentrifugation, small angle neutron and X-ray scattering, density) and crystallography, and protein dynamics by energy resolved neutron scattering. This review concerns work from our laboratory on (i) proteins from extreme halophilic Archaea, and (ii) psychrophile, mesophile, thermophile and hyperthermophile bacterial cells.

  9. Metal nanoelectrodes for molecular transistor and investigation of electron transport in molecular systems

    NASA Astrophysics Data System (ADS)

    Suyatin, D. B.; Soldatov, E. S.; Maximov, Ivan; Montelius, Lars; Samuelson, Lars; Khomutov, G. B.; Gubin, S. P.; Sergeev-Cherenkov, A. N.

    2002-06-01

    Gold nanoelectrodes with gaps of less than 10 nm were formed by conventional E-beam lithography on silicon substrates covered by Al2O3. Molecular films were deposited on the electrodes by Langmuir-Shaefer technique. The I-V curves of such systems show a suppressed conductance indicating a correlated electron tunnelling through the system. All measurements were made at room temperature.

  10. Metal nanoelectrodes for molecular transistor and investigation of electron transport in molecular systems

    NASA Astrophysics Data System (ADS)

    Suyatin, D. B.; Soldatov, E. S.; Maximov, Ivan; Montelius, Lars; Samuelson, Lars; Khomutov, G. B.; Gubin, S. P.; Sergeev-Cherenkov, A. N.

    2003-06-01

    Gold nanoelectrodes with gaps of less than 10 nm were formed by conventional E-beam lithography on silicon substrates covered by Al2O3. Molecular films were deposited on the electrodes by Langmuir-Shaefer technique. The I-V curves of such systems show a suppressed conductance indicating a correlated electron tunnelling through the system. All measurements were made at room temperature.

  11. Cloning Yeast Actin cDNA Leads to an Investigative Approach for the Molecular Biology Laboratory

    ERIC Educational Resources Information Center

    Black, Michael W.; Tuan, Alice; Jonasson, Erin

    2008-01-01

    The emergence of molecular tools in multiple disciplines has elevated the importance of undergraduate laboratory courses that train students in molecular biology techniques. Although it would also be desirable to provide students with opportunities to apply these techniques in an investigative manner, this is generally not possible in the…

  12. Interaction investigations of crustacean β-GBP recognition toward pathogenic microbial cell membrane and stimulate upon prophenoloxidase activation.

    PubMed

    Sivakamavalli, Jeyachandran; Selvaraj, Chandrabose; Singh, Sanjeev Kumar; Vaseeharan, Baskaralingam

    2014-04-01

    In invertebrates, crustaceans' immune system consists of pattern recognition receptors (PRRs) instead of immunoglobulin's, which involves in the microbial recognition and initiates the protein-ligand interaction between hosts and pathogens. In the present study, PRRs namely β-1,3 glucan binding protein (β-GBP) from mangrove crab Episesarma tetragonum and its interactions with the pathogens such as bacterial and fungal outer membrane proteins (OMP) were investigated through microbial aggregation and computational interaction studies. Molecular recognition and microbial aggregation results of Episesarma tetragonum β-GBP showed the specific binding affinity toward the fungal β-1,3 glucan molecule when compared to other bacterial ligands. Because of this microbial recognition, prophenoloxidase activity was enhanced and triggers the innate immunity inside the host animal. Our findings disclose the role of β-GBP in molecular recognition, host-pathogen interaction through microbial aggregation, and docking analysis. In vitro results were concurred with the in silico docking, and molecular dynamics simulation analysis. This study would be helpful to understand the molecular mechanism of β-GBP and update the current knowledge on the PRRs of crustaceans.

  13. Interferons and viruses: an evolutionary arms race of molecular interactions

    PubMed Central

    Hoffmann, Hans-Heinrich; Schneider, William M.; Rice, Charles M.

    2015-01-01

    Over half a century has passed since interferons (IFNs) were discovered and shown to inhibit virus infection in cultured cells. Since then, researchers have steadily brought to light the molecular details of IFN signaling, catalogued their pleiotropic effects on cells, and harnessed their therapeutic potential for a variety of maladies. While advances have been plentiful, several fundamental questions have yet to be answered and much complexity remains to be unraveled. We explore the current knowledge surrounding four main questions: are type I IFN subtypes differentially produced in response to distinct pathogens? How are IFN subtypes distinguished by cells? What are the mechanisms and consequences of viral antagonism? Lastly, how can the IFN response be harnessed to improve vaccine efficacy? PMID:25704559

  14. Interplay between molecular conformation and intermolecular interactions in conformational polymorphism: a molecular perspective from electronic calculations of tolfenamic acid.

    PubMed

    Mattei, Alessandra; Li, Tonglei

    2011-10-14

    Tolfenamic acid exhibits conformational polymorphism. The molecules in its two commonly occurred crystal structures form similar hydrogen-bonded dimers but differ in conformation. The conformational variance was analyzed by electronic calculation methods with the aim to unravel intrinsic connection between the conformational flexibility and intermolecular interactions in the polymorphs. The study was conducted mainly by conceptual density functional theory (DFT) and natural bond orbital (NBO) analysis. It is found that the conformational polymorphism is resulted from the energy competition between intramolecular π-conjugation and intermolecular hydrogen bonding. By adapting conformation that departs from being the most energetically stable, tolfenamic acid molecules can strengthen the intermolecular hydrogen-bonding interactions in the crystals. The study illustrates how the molecule's electronic properties are influenced by conformational variation and, inherently, how the intermolecular interactions become regulated. Moreover, understanding molecular interaction and crystal packing necessitates electronic structure calculation and analysis, which can be further facilitated by utilizing DFT and NBO concepts.

  15. Single molecule switches and molecular self-assembly: Low temperature STM investigations and manipulations

    NASA Astrophysics Data System (ADS)

    Iancu, Violeta

    This dissertation is devoted to single molecule investigations and manipulations of two porphyrin-based molecules, chlorophyll-a and Co-porphyrin. The molecules are adsorbed on metallic substrates and studied at low temperatures using a scanning tunneling microscope. The electronic, structural and mechanical properties of the molecules are investigated in detail with atomic level precision. Chlorophyll-a is the key ingredient in photosynthesis processes while Co-porphyrin is a magnetic molecule that represents the recent emerging field of molecular spintronics. Using the scanning tunneling microscope tip and the substrate as electrodes, and the molecules as active ingredients, single molecule switches made of these two molecules are demonstrated. The first switch, a multiple and reversible mechanical switch, is realized by using chlorophyll-a where the energy transfer of a single tunneling electron is used to rotate a C-C bond of the molecule's tail on a Au(111) surface. Here, the detailed underlying switching mechanisms are uncovered from the statistical analyses conducted over 1200 switching events together with the support of geometrically relaxed parametric calculations. The second switch, a spintronic switch, uses Co-porphyrin conformational changes to tune the spin-electron interaction between the Co atom and Cu(111) electrons. A change in the molecular conformation, from saddle to planar, leads to enhanced spin-electron coupling strength, and consequently, elevated Kondo temperatures. Self-assembly process is exploited for both the molecules and the analyses reveal important information regarding the layer growth and the electronic differences that appear due to the modified molecule-substrate environment.

  16. Molecular spin on surface: From strong correlation to dispersion interactions

    NASA Astrophysics Data System (ADS)

    Zhang, Yachao

    2016-09-01

    A reliable prediction of magnetic properties of surface-supported molecules containing 3d/4f spin carriers has challenged the electronic structure theory for decades. Here we tackle this problem with Hubbard-U corrected van der Waals density functional (vdW-DF), incorporating strong correlation effects of the localized electrons and dispersion interactions involved in the molecule-surface binding. By fitting the spin state energetics of a series of Fe(ii) compounds with varying ligand field strength, we find that the optimal U value for vdW-DF is much smaller than that for the local density approximation (LDA) while quite similar to that for the generalized gradient approximation (GGA). We show that although vdW-DF+U overestimates largely the metal-ligand bond distance, the predicted adiabatic high-spin-low-spin energy splitting ΔEHL is only slightly changed with respect to that obtained using the LDA+U geometries consistent with experiment. Then we use Cu(111)-supported metallocene (M(C5H5)2, M = Fe, and Co) as a prototype example to explore the effects of the molecule-surface interactions. We show that the non-local dispersion interactions, poorly described by LDA and GGA while reasonably captured by vdW-DF, are critical for reproducing ΔEHL at large molecule-surface distances. Besides, we find that ΔEHL is decreased by the molecule-metal contact, which is shown to weaken the local ligand field around the magnetic center.

  17. The interaction of plant-growth regulators with serum albumin: molecular modeling and spectroscopic methods.

    PubMed

    Dong, Sheying; Li, Zhiqin; Shi, Ling; Huang, Guiqi; Chen, Shuangli; Huang, Tinglin

    2014-05-01

    The affinity between two plant-growth regulators (PGRs) and human serum albumin (HSA) was investigated by molecular modeling techniques and spectroscopic methods. The results of molecular modeling simulations revealed that paclobutrazol (PAC) could bind on both site I and site II in HSA where the interaction was easier, while uniconazole (UNI) could not bind with HSA. Furthermore, the results of fluorescence spectroscopy, three-dimensional (3D) fluorescence spectroscopy and circular dichroism (CD) spectroscopy suggested that PAC had a strong ability to quench the intrinsic fluorescence of HSA. The binding affinity (Kb) and the amounts of binding sites (n) between PAC and HSA at 291 K were estimated as 2.37×10(5) mol L(-1) and 1, respectively, which confirm that PAC mainly binds on site II of HSA. An apparent distance between the Trp214 and PAC was 4.41 nm. Additionally, the binding of PAC induced the conformational changes of disulfide bridges of HSA with the decrease of α-helix content. These studies provide more information on the potential toxicological effects and environmental risk assessment of PGRs.

  18. Interaction of cinnamic acid derivatives with β-cyclodextrin in water: experimental and molecular modeling studies.

    PubMed

    Liu, Benguo; Zeng, Jie; Chen, Chen; Liu, Yonglan; Ma, Hanjun; Mo, Haizhen; Liang, Guizhao

    2016-03-01

    Cyclodextrins (CDs) can be used to improve the solubility and stability of cinnamic acid derivatives (CAs). However, there was no detailed report about understanding the effects of the substituent groups in the benzene ring on the inclusion behavior between CAs and CDs in aqueous solution. Here, the interaction of β-CD with CAs, including caffeic acid, ferulic acid, and p-coumaric acid, in water was investigated by phase-solubility method, UV, fluorescence, and (1)H NMR spectroscopy, together with ONIOM (our Own N-layer Integrated Orbital molecular Mechanics)-based QM/MM (Quantum Mechanics/Molecular Mechanics) calculations. Experimental results demonstrated that CAs could form 1:1 stoichiometric inclusion complex with β-CD by non-covalent bonds, and that the maximum apparent stability constants were found in caffeic acid (176M(-1)) followed by p-coumaric acid (160M(-1)) and ferulic acid (133M(-1)). Moreover, our calculations reasonably illustrated the binding orientations of β-CD with CAs determined by experimental observations.

  19. Spectroscopy, calorimetry and molecular simulation studies on the interaction of catalase with copper ion.

    PubMed

    Hao, Fang; Jing, Mingyang; Zhao, Xingchen; Liu, Rutao

    2015-02-01

    In this research, the binding mechanism of Cu(2+) to bovine liver catalase (BLC) was studied by fluorescence spectroscopy, ultraviolet-visible (UV-vis) absorption spectroscopy, circular dichroism (CD) spectroscopy, isothermal titration calorimetry (ITC) and molecular docking methods. The cellar experiment was firstly carried out to investigate the inhibition effect of catalase. During the fluorescence quenching study, after correcting the inner filter effect (IFE), the fluorescence of BLC was found to be quenched by Cu(2+). The quenching mechanism was determined by fluorescence lifetime measurement, and was confirmed to be the dynamic mode. The secondary structure content of BLC was changed by the addition of Cu(2+), as revealed by UV-vis absorption and CD spectra, which further induces the decrease in BLC activity. Molecular simulation study indicates that Cu(2+) is located between two β-sheets and two random coils of BLC near to the heme group, and interacts with His 74 and Ser 113 residues near a hydrophilic area. The decrease of α-helix and the binding of His 74 are considered to be the major reason for the inhibition of BLC activity caused by Cu(2+). The ITC results indicate that the binding stoichiometry of Cu(2+) to catalase is 11.4. Moreover, the binding of Cu(2+) to BLC destroyed H-bonds, which was confirmed by the CD result.

  20. Spectroscopy, calorimetry and molecular simulation studies on the interaction of catalase with copper ion.

    PubMed

    Hao, Fang; Jing, Mingyang; Zhao, Xingchen; Liu, Rutao

    2015-02-01

    In this research, the binding mechanism of Cu(2+) to bovine liver catalase (BLC) was studied by fluorescence spectroscopy, ultraviolet-visible (UV-vis) absorption spectroscopy, circular dichroism (CD) spectroscopy, isothermal titration calorimetry (ITC) and molecular docking methods. The cellar experiment was firstly carried out to investigate the inhibition effect of catalase. During the fluorescence quenching study, after correcting the inner filter effect (IFE), the fluorescence of BLC was found to be quenched by Cu(2+). The quenching mechanism was determined by fluorescence lifetime measurement, and was confirmed to be the dynamic mode. The secondary structure content of BLC was changed by the addition of Cu(2+), as revealed by UV-vis absorption and CD spectra, which further induces the decrease in BLC activity. Molecular simulation study indicates that Cu(2+) is located between two β-sheets and two random coils of BLC near to the heme group, and interacts with His 74 and Ser 113 residues near a hydrophilic area. The decrease of α-helix and the binding of His 74 are considered to be the major reason for the inhibition of BLC activity caused by Cu(2+). The ITC results indicate that the binding stoichiometry of Cu(2+) to catalase is 11.4. Moreover, the binding of Cu(2+) to BLC destroyed H-bonds, which was confirmed by the CD result. PMID:25618814

  1. Molecular interaction and energy transfer between human serum albumin and bioactive component Aloe dihydrocoumarin

    NASA Astrophysics Data System (ADS)

    Zhang, Xiu-Feng; Xie, Ling; Liu, Yang; Xiang, Jun-Feng; Li, Lin; Tang, Ya-Lin

    2008-10-01

    Aloe dihydrocoumarin is an antioxidant and a candidate of immunomodulatory drug on the immune system and can balance physiological reactive oxygen species (ROS) levels which may be useful to maintain homeostasis. In order to explore the mechanism of drug action at a molecular level, the binding of Aloe dihydrocoumarin with human serum albumin (HSA) has been investigated by fluorescence, ultraviolet (UV), circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopy, fluorescence dynamics, and molecular dynamic docking for the first time. We observed a quenching of fluorescence of HSA in the presence of Aloe dihydrocoumarin and also analyzed the quenching results using the Stern-Volmer equation and obtained high affinity binding to HSA. A Förster type fluorescence resonance energy transfer mechanism is involved in this quenching of Trp fluorescence by Aloe dihydrocoumarin. From the CD and FT-IR results, it is apparent that the interaction of Aloe dihydrocoumarin with HSA causes a conformational change of the protein, with the loss of α-helix stability and the gain of β-sheet and β-turn content. Data obtained by fluorescence spectroscopy, fluorescence dynamics, CD, and FT-IR experiments along with the docking studies suggest that Aloe dihydrocoumarin binds to residues located in subdomain IIA of HSA.

  2. Molecular Modeling of Interaction between Diabetic Drug and Antioxidant in Controlling Sucrose

    NASA Astrophysics Data System (ADS)

    Rakesh, Leela; Lee, Choon

    2009-09-01

    This article examined the possible protective effect of N-acetylcysteine (NAC) taurine, quercetin and Syringaldehyde dendritic antioxidants against the oxidative stress induced by diabetic or pre-diabetic patient case due to high sucrose intake by computer simulation. We also compared these results with the well-known diabetic drugs glizipid and Avandia. Towards this understanding we undertook a molecular level computer model in order to study the molecular interaction between high sugar content with antioxidant by varying ratios of sucrose molecules with and without the presence of diabetic drugs. From our study it shows that with the presence of various antioxidant combinations diabetics drugs could be much more beneficial to the patients in terms of its side effects such a heart attack. Many interesting results have been obtained by this study. The application of this driving force may be used to predict the feasibility and benefit in order to understand the high-sucrose diet-induced obesity, which certainly would bring new insights on obesity-related adverse control and may possibly suggest the impact of N-acetylcysteine and syringaldehyde in such cases. Hyperglycemia is an important predictor of cardiovascular mortality in patients with diabetes. We also investigated the hypothesis that diabetes or acute hyperglycemia attenuates the reduction of myocardial infarct size produced by activation of mitochondrial ATP-regulated potassium (KATP) channels. The results indicate that diabetes/hyperglycemia impairs activation of mitochondrial KATP channels.

  3. Modelling social interaction as perceptual crossing: an investigation into the dynamics of the interaction process

    NASA Astrophysics Data System (ADS)

    Froese, Tom; Di Paolo, Ezequiel A.

    2010-03-01

    This paper continues efforts to establish a mutually informative dialogue between psychology and evolutionary robotics in order to investigate the dynamics of social interaction. We replicate a recent simulation model of a minimalist experiment in perceptual crossing and confirm the results with significantly simpler artificial agents. A series of psycho-physical tests of their behaviour informs a hypothetical circuit model of their internal operation. However, a detailed study of the actual internal dynamics reveals this circuit model to be unfounded, thereby offering a tale of caution for those hypothesising about sub-personal processes in terms of behavioural observations. In particular, it is shown that the behaviour of the agents largely emerges out of the interaction process itself rather than being an individual achievement alone. We also extend the original simulation model in two novel directions in order to test further the extent to which perceptual crossing between agents can self-organise in a robust manner. These modelling results suggest new hypotheses that can become the basis for further psychological experiments.

  4. Investigations of Mechanical Properties of Polymer Brushes and Hydrogels Through Molecular Dynamics Simulation

    NASA Astrophysics Data System (ADS)

    Ou, Yangpeng

    In this thesis, the forces between surfaces coated with polyelectrolye brushes and polymer gels were investigated via molecular dynamics simulation on a computer workstation that I built. The first project investigated the reasons for why grafted polyelectrolye brushes have smaller friction coefficients than grafted neutral polymer brushes. The flexible neutral polymer brush is treated as a bead-spring model, and the polyelectrolyte brush is treated the same way except that each bead is charged and there are counterions present to neutralize the charge. We investigated the friction coefficient, monomer density, and brush penetration for the two kinds of brushes with both the same grafting density and the same normal force under good solvent conditions. We found that polyelectrolyte brushes have smaller friction coefficients in both simulations. We present evidence that the reason for this is that the extra normal force contribution provided by the counterion osmotic pressure that exists for polyelectrolyte brushes permits them to support the same load as identical neutral polymer brushes of higher grafting density. Because of the resulting lower monomer density for the charged brushes, fewer monomer collisions take place per unit time, resulting in a lower friction coefficient. The second project investigated interactions between two grafted polymer gels. Unlike polyelectrolyte polymer brushes, polymer chains are linked to other neighboring polymer chains. We studied a defect-free network of diamond-like topology containing 8 tetra-functional nodes linked by 16 non-crossing chains. We studied the shear force, friction coefficient, and density profiles of these polymer gels. We found that polymer gels have very small friction coefficients in our simulation, which is consistent with previous experimental measurements. In order to understand and explain this very low friction coefficient behavior, we computed the interpenetrations between two polymer gels, the

  5. "Rules of Engagement" of Protein-Glycoconjugate Interactions: A Molecular View Achievable by using NMR Spectroscopy and Molecular Modeling.

    PubMed

    Marchetti, Roberta; Perez, Serge; Arda, Ana; Imberty, Anne; Jimenez-Barbero, Jesus; Silipo, Alba; Molinaro, Antonio

    2016-08-01

    Understanding the dynamics of protein-ligand interactions, which lie at the heart of host-pathogen recognition, represents a crucial step to clarify the molecular determinants implicated in binding events, as well as to optimize the design of new molecules with therapeutic aims. Over the last decade, advances in complementary biophysical and spectroscopic methods permitted us to deeply dissect the fine structural details of biologically relevant molecular recognition processes with high resolution. This Review focuses on the development and use of modern nuclear magnetic resonance (NMR) techniques to dissect binding events. These spectroscopic methods, complementing X-ray crystallography and molecular modeling methodologies, will be taken into account as indispensable tools to provide a complete picture of protein-glycoconjugate binding mechanisms related to biomedicine applications against infectious diseases. PMID:27547635

  6. "Rules of Engagement" of Protein-Glycoconjugate Interactions: A Molecular View Achievable by using NMR Spectroscopy and Molecular Modeling.

    PubMed

    Marchetti, Roberta; Perez, Serge; Arda, Ana; Imberty, Anne; Jimenez-Barbero, Jesus; Silipo, Alba; Molinaro, Antonio

    2016-08-01

    Understanding the dynamics of protein-ligand interactions, which lie at the heart of host-pathogen recognition, represents a crucial step to clarify the molecular determinants implicated in binding events, as well as to optimize the design of new molecules with therapeutic aims. Over the last decade, advances in complementary biophysical and spectroscopic methods permitted us to deeply dissect the fine structural details of biologically relevant molecular recognition processes with high resolution. This Review focuses on the development and use of modern nuclear magnetic resonance (NMR) techniques to dissect binding events. These spectroscopic methods, complementing X-ray crystallography and molecular modeling methodologies, will be taken into account as indispensable tools to provide a complete picture of protein-glycoconjugate binding mechanisms related to biomedicine applications against infectious diseases.

  7. Modeling of inhibitor-metalloenzyme interactions and selectivity using molecular mechanics grounded in quantum chemistry.

    PubMed

    Garmer, D R; Gresh, N; Roques, B P

    1998-04-01

    We investigated the binding properties of the metalloprotease inhibitors hydroxamate, methanethiolate, and methylphosphoramidate to a model coordination site occurring in several Zn2+ metalloproteases, including thermolysin. This was carried out using both the SIBFA (sum of interactions between fragments ab initio-computed) molecular mechanics and the SCF/MP2 procedures for the purpose of evaluating SIBFA as a metalloenzyme modeling tool. The energy-minimized structures were closely similar to the X-ray crystallographic structures of related thermolysin-inhibitor complexes. We found that selectivity between alternative geometries and between inhibitors usually stemmed from multiple interaction components included in SIBFA. The binding strength sequence is hydroxamate > methanethiolate > or = methylphosphoramidate from multiple interaction components included in SIBFA. The trends in interaction energy components, rankings, and preferences for mono- or bidentate binding were consistent in both computational procedures. We also compared the Zn2+ vs. Mg2+ selectivities in several other polycoordinated sites having various "hard" and "soft" qualities. This included a hexahydrate, a model representing Mg2+/Ca2+ binding sites, a chlorophyll-like structure, and a zinc finger model. The latter three favor Zn2+ over Mg2+ by a greater degree than the hydrated state, but the selectivity varies widely according to the ligand "softness." SIBFA was able to match the ab initio binding energies by < 2%, with the SIBFA terms representing dispersion and charge-transfer contributing the most to Zn2+/Mg2+ selectivity. These results showed this procedure to be a very capable modeling tool for metalloenzyme problems, in this case giving valuable information about details and limitations of "hard" and "soft" selectivity trends.

  8. Disk-Halo interaction: The molecular clouds in the Galactic center region

    NASA Astrophysics Data System (ADS)

    Riquelme, D.; Martín-Pintado, J.; Mauersberger, R.; Amo-Baladrón, M. A.; Martín, S.; Bronfman, L.

    2012-07-01

    From a large-scale study of the Galactic center (GC) region in SiO(2 - 1), HCO+(1 - 0), and H13CO+(1 - 0), we identify shock regions as traced by the enhancement of SiO emission. We selected 9 positions called by us as "interaction regions", because they mark the places where gas in the GC could be interacting with gas coming from higher latitude ("disk-halo interaction") or from larger galactocentric radius. These positions were studied using the 12C/13C isotopic ratio to trace gas accretion/ejection. We found a systematically higher 12C/13C isotopic ratio (> 40) toward the interaction regions than for the GC "standard" molecular clouds (20 - 25). These high isotopic ratios are consistent with the accretion of the gas from higher galactic latitudes or from larger galactocentric distances. There are two kinetic temperature regimes (one warm at ~ 200 K and one cold at ~ 40 K) for all the positions, except for the positions associated to the giant molecular loops where only the warm component is present. Relative molecular abundances suggest that the heating mechanism in the GC is related to shocks. We mapped one molecular cloud placed at the foot points of the giant molecular loops in 3-mm molecular lines to reveal the morphology, chemical composition and the kinematics of the shocked gas.

  9. Cellular microbiology and molecular ecology of Legionella-amoeba interaction.

    PubMed

    Richards, Ashley M; Von Dwingelo, Juanita E; Price, Christopher T; Abu Kwaik, Yousef

    2013-05-15

    Legionella pneumophila is an aquatic organism that interacts with amoebae and ciliated protozoa as the natural hosts, and this interaction plays a central role in bacterial ecology and infectivity. Upon transmission to humans, L. pneumophila infect and replicate within alveolar macrophages causing pneumonia. Intracellular proliferation of L. pneumophila within the two evolutionarily distant hosts is facilitated by bacterial exploitation of evolutionarily conserved host processes that are targeted by bacterial protein effectors injected into the host cell by the Dot/Icm type VIB translocation system. Although cysteine is semi-essential for humans and essential for amoeba, it is a metabolically favorable source of carbon and energy generation by L. pneumophila. To counteract host limitation of cysteine, L. pneumophila utilizes the AnkB Dot/Icm-translocated F-box effector to promote host proteasomal degradation of polyubiquitinated proteins within amoebae and human cells. Evidence indicates ankB and other Dot/Icm-translocated effector genes have been acquired through inter-kingdom horizontal gene transfer.

  10. Cellular microbiology and molecular ecology of Legionella-amoeba interaction.

    PubMed

    Richards, Ashley M; Von Dwingelo, Juanita E; Price, Christopher T; Abu Kwaik, Yousef

    2013-05-15

    Legionella pneumophila is an aquatic organism that interacts with amoebae and ciliated protozoa as the natural hosts, and this interaction plays a central role in bacterial ecology and infectivity. Upon transmission to humans, L. pneumophila infect and replicate within alveolar macrophages causing pneumonia. Intracellular proliferation of L. pneumophila within the two evolutionarily distant hosts is facilitated by bacterial exploitation of evolutionarily conserved host processes that are targeted by bacterial protein effectors injected into the host cell by the Dot/Icm type VIB translocation system. Although cysteine is semi-essential for humans and essential for amoeba, it is a metabolically favorable source of carbon and energy generation by L. pneumophila. To counteract host limitation of cysteine, L. pneumophila utilizes the AnkB Dot/Icm-translocated F-box effector to promote host proteasomal degradation of polyubiquitinated proteins within amoebae and human cells. Evidence indicates ankB and other Dot/Icm-translocated effector genes have been acquired through inter-kingdom horizontal gene transfer. PMID:23535283

  11. Immobilization and molecular interactions between bacteriophage and lipopolysaccharide bilayers.

    PubMed

    Handa, Hitesh; Gurczynski, Stephen; Jackson, Matthew P; Mao, Guangzhao

    2010-07-20

    The paper describes immobilization methods of bacteriophage P22 and tailspike gp9 proteins isolated from P22 on atomic force microscope (AFM) probes. The paper also reports single molecule force spectroscopy (SMFS) using AFM of the immobilized P22 (or gp9) interactions with substrate-supported O-antigenic lipopolysaccharides (LPS) bilayers. LPS covers the outer membrane of gram-negative bacteria, such as Salmonella typhimurium. Evidence from AFM imaging and SMFS shows that immobilized P22 (or gp9) are capable of strong and multivalent binding to supported LPS. The most common rupture forces between P22 and LPS were identified to be 72, 130, 206, and 279 pN at force loading rate of 12,000 pN/s. The quantized unbinding force was found to decrease with decreasing force loading rate as predicted by the Bell model. By fitting the force data with the Bell model, an energy barrier of 55 kJ/mol was obtained. Evidence is also provided that demonstrates the resilience of phage to pH and temperature fluctuation as well as dehydration/rehydration cycles. The biospecific interactions between P22 and the LPS are relevant to cell infection, inflammation, cancer progression and metastasis, food safety, pharmaceuticals, and biosensor development. PMID:20481467

  12. Cataloging the biomedical world of pain through semi-automated curation of molecular interactions.

    PubMed

    Jamieson, Daniel G; Roberts, Phoebe M; Robertson, David L; Sidders, Ben; Nenadic, Goran

    2013-01-01

    The vast collection of biomedical literature and its continued expansion has presented a number of challenges to researchers who require structured findings to stay abreast of and analyze molecular mechanisms relevant to their domain of interest. By structuring literature content into topic-specific machine-readable databases, the aggregate data from multiple articles can be used to infer trends that can be compared and contrasted with similar findings from topic-independent resources. Our study presents a generalized procedure for semi-automatically creating a custom topic-specific molecular interaction database through the use of text mining to assist manual curation. We apply the procedure to capture molecular events that underlie 'pain', a complex phenomenon with a large societal burden and unmet medical need. We describe how existing text mining solutions are used to build a pain-specific corpus, extract molecular events from it, add context to the extracted events and assess their relevance. The pain-specific corpus contains 765 692 documents from Medline and PubMed Central, from which we extracted 356 499 unique normalized molecular events, with 261 438 single protein events and 93 271 molecular interactions supplied by BioContext. Event chains are annotated with negation, speculation, anatomy, Gene Ontology terms, mutations, pain and disease relevance, which collectively provide detailed insight into how that event chain is associated with pain. The extracted relations are visualized in a wiki platform (wiki-pain.org) that enables efficient manual curation and exploration of the molecular mechanisms that underlie pain. Curation of 1500 grouped event chains ranked by pain relevance revealed 613 accurately extracted unique molecular interactions that in the future can be used to study the underlying mechanisms involved in pain. Our approach demonstrates that combining existing text mining tools with domain-specific terms and wiki-based visualization can

  13. Cataloging the biomedical world of pain through semi-automated curation of molecular interactions.

    PubMed

    Jamieson, Daniel G; Roberts, Phoebe M; Robertson, David L; Sidders, Ben; Nenadic, Goran

    2013-01-01

    The vast collection of biomedical literature and its continued expansion has presented a number of challenges to researchers who require structured findings to stay abreast of and analyze molecular mechanisms relevant to their domain of interest. By structuring literature content into topic-specific machine-readable databases, the aggregate data from multiple articles can be used to infer trends that can be compared and contrasted with similar findings from topic-independent resources. Our study presents a generalized procedure for semi-automatically creating a custom topic-specific molecular interaction database through the use of text mining to assist manual curation. We apply the procedure to capture molecular events that underlie 'pain', a complex phenomenon with a large societal burden and unmet medical need. We describe how existing text mining solutions are used to build a pain-specific corpus, extract molecular events from it, add context to the extracted events and assess their relevance. The pain-specific corpus contains 765 692 documents from Medline and PubMed Central, from which we extracted 356 499 unique normalized molecular events, with 261 438 single protein events and 93 271 molecular interactions supplied by BioContext. Event chains are annotated with negation, speculation, anatomy, Gene Ontology terms, mutations, pain and disease relevance, which collectively provide detailed insight into how that event chain is associated with pain. The extracted relations are visualized in a wiki platform (wiki-pain.org) that enables efficient manual curation and exploration of the molecular mechanisms that underlie pain. Curation of 1500 grouped event chains ranked by pain relevance revealed 613 accurately extracted unique molecular interactions that in the future can be used to study the underlying mechanisms involved in pain. Our approach demonstrates that combining existing text mining tools with domain-specific terms and wiki-based visualization can

  14. Cataloging the biomedical world of pain through semi-automated curation of molecular interactions

    PubMed Central

    Jamieson, Daniel G.; Roberts, Phoebe M.; Robertson, David L.; Sidders, Ben; Nenadic, Goran

    2013-01-01

    The vast collection of biomedical literature and its continued expansion has presented a number of challenges to researchers who require structured findings to stay abreast of and analyze molecular mechanisms relevant to their domain of interest. By structuring literature content into topic-specific machine-readable databases, the aggregate data from multiple articles can be used to infer trends that can be compared and contrasted with similar findings from topic-independent resources. Our study presents a generalized procedure for semi-automatically creating a custom topic-specific molecular interaction database through the use of text mining to assist manual curation. We apply the procedure to capture molecular events that underlie ‘pain’, a complex phenomenon with a large societal burden and unmet medical need. We describe how existing text mining solutions are used to build a pain-specific corpus, extract molecular events from it, add context to the extracted events and assess their relevance. The pain-specific corpus contains 765 692 documents from Medline and PubMed Central, from which we extracted 356 499 unique normalized molecular events, with 261 438 single protein events and 93 271 molecular interactions supplied by BioContext. Event chains are annotated with negation, speculation, anatomy, Gene Ontology terms, mutations, pain and disease relevance, which collectively provide detailed insight into how that event chain is associated with pain. The extracted relations are visualized in a wiki platform (wiki-pain.org) that enables efficient manual curation and exploration of the molecular mechanisms that underlie pain. Curation of 1500 grouped event chains ranked by pain relevance revealed 613 accurately extracted unique molecular interactions that in the future can be used to study the underlying mechanisms involved in pain. Our approach demonstrates that combining existing text mining tools with domain-specific terms and wiki-based visualization can

  15. Interaction of two different types of membrane proteins with model membranes investigated by FTIR ATR spectroscopy

    NASA Astrophysics Data System (ADS)

    Siam, M.; Reiter, G.; Schwarzott, M.; Baurecht, D.; Fringeli, U. P.

    1998-06-01

    Polarized FTIR ATR spectroscopy was used to investigate the interaction of mitochondrial creatine kinase (Mi-CK) and intestinal alkaline phosphatase (AP) with model membrane assemblies. Mi-CK was immobilized by adsorption to the negatively charged cardiolipin (CL) leaflet of a supported CL/DPPA bilayer. H-D-exchange of the enzyme and the stability under flowthrough conditions of the protein/membrane assembly were examined. AP, however, was bound to a DPPA Langmuir-Blodgett layer (LBL), followed by the completion of a bilayer-like structure by adsorption of POPC molecules from a vesicular solution. It turned out that the POPC adsorbate exhibited decreased molecular order compared to the POPC molecules on a supported POPC/DPPA bilayer. Enzymatic activity of immobilized AP was determined with p-nitrophenyl phosphate (p-NPP) as substrate and remained unchanged for at least 2 days.

  16. A facility for investigating interactions of energetic atomic oxygen with solids

    NASA Technical Reports Server (NTRS)

    Arnold, G. S.; Peplinski, D. R.

    1984-01-01

    A facility for the investigation of the interactions of energetic atomic oxygen with solids is described. The facility is comprised of a four-chambered, differentially pumped molecular beam apparatus which can be equipped with one of a variety of sources of atomic oxygen. The primary source is a dc arch-heated supersonic nozzle source which produces a flux of atomic oxygen in excess of 10 to the 15th power/cu cm/sec at the target, at a velocity of 3.5 km/sec. Results of applications of this facility to the study of the reactions of atomic oxygen with carbon and polyimide films are briefly reviewed and compared to data obtained on various flights of the space shuttle.

  17. Theoretical investigation of the interaction of glycerol with aluminum and magnesium phthalocyanines.

    PubMed

    Silva, V H C; Camargo, L T F M; Napolitano, H B; Pérez, C N; Camargo, A J

    2010-09-01

    Glycerol is a byproduct produced in great quantity by biodiesel industries in transesterification reactions. Finding new applications for glycerol is a current concern of many research groups around the world. This work focuses on a theoretical investigation, at the B3LYP/6-31G* level of theory, into the possibility of using aluminum phthalocyanine (AlPc) and magnesium phthalocyanine (MgPc) in the modelling of catalysts to convert glycerol into alcohol, which has wider industrial applicability. According to our calculations there are strong interactions between the O-terminus of glycerol and the central metal atom of AlPc and MgPc. By applying the Fukui function, HSAB theory and analysis of the frontier molecular orbital, it was possible to explain the way in which glycerol interacts with AlPc and MgPc. As a result of these interactions, there is a considerable change in both electronic and geometric parameters of glycerol, which can be used in designing new strategies to convert glycerol into alcohol. PMID:20655256

  18. Extremely Strong Interaction of Sodium Decyl Sulfate and Decyltrimethylammonium Bromide in Molecular Aggregates

    PubMed

    Matsuki; Aratono; Kaneshina; Motomura

    1997-07-01

    The thermodynamic behavior of a mixture of sodium decyl sulfate (SDeS) and decyltrimethylammonium bromide (DeTAB) in aqueous solution and in molecular aggregates such as surface adsorbed films and micelles was investigated by measuring the electric conductivity and surface tension of the aqueous solutions. The thermodynamic quantities in solution and those in the molecular aggregates were evaluated from the experimental conductivity and surface tension data. The results for molar conductivity showed that dimerization or ion-pair formation of the SDeS and DeTAB molecules does not occur in aqueous solution and the mixture behaves as uni-univalent strong electrolyte below the critical micelle concentration (CMC). Contrary to the results in the aqueous solution, we found significant nonideal behavior in the phase diagrams of surface adsorption; that is, equimolar mixture of SDeS and DeTAB exists in the adsorbed film at almost all compositions irrespective of the bulk composition in the solution. The same result was also observed in the phase diagram of micelle formation. There was no difference in phase diagrams between surface adsorption and micelle formation at the CMC. The great nonideal mixing of SDeS and DeTAB in the molecular aggregates is undoubtedly attributable to the extreme attractive interaction between oppositely charged polar head groups of surfactants as well as to cohesion between hydrophobic groups. Further, in a low concentration region, it turned out that equimolar composition is preserved in the film during phase transition of the mixed adsorbed film of SDeS and DeTAB from a gaseous state to an expanded state.

  19. Unraveling microalgal molecular interactions using evolutionary and structural bioinformatics.

    PubMed

    Vlachakis, Dimitrios; Pavlopoulou, Athanasia; Kazazi, Dorothea; Kossida, Sophia

    2013-10-10

    Microalgae are unicellular microorganisms indispensible for environmental stability and life on earth, because they produce approximately half of the atmospheric oxygen, with simultaneously feeding on the harmful greenhouse gas carbon dioxide. Using gene fusion analysis, a series of five fusion/fission events was identified, that provided the basis for critical insights to their evolutionary history. Moreover, the three-dimensional structures of both the fused and the component proteins were predicted, allowing us to envisage putative protein-protein interactions that are invaluable for the efficient usage, handling and exploitation of microalgae. Collectively, our proposed approach on the five fusion/fission alga protein events contributes towards the expansion of the microalgae knowledgebase, bridging protein evolution of the ancient microalgal species and the rapidly evolving, modern, bioinformatics field.

  20. Molecular interactions between albumin and proximal tubular cells.

    PubMed

    Brunskill, N J

    1998-01-01

    In glomerular diseases the filtration of excess proteins into the proximal tubule, together with their subsequent reabsorption may represent an important pathological mechanism underlying progressive renal scarring. The most prominent protein in glomerular filtrate, albumin, is reabsorbed by receptor-mediated endocytosis by proximal tubular cells. It binds both to scavenger-type receptors and to megalin in the proximal tubule. Some of these receptors appear to be shared with other cell types, particularly endothelial cells. The endocytic uptake of albumin is subjected to complex hormonal and enzymatic regulation. In addition to being reabsorbed in the proximal tubule, albumin may act as a signalling molecule in these cells, and may induce the expression of numerous pro-inflammatory genes. Modulation of the interaction of albumin with proximal tubular cells may eventually prove to be of therapeutic importance in the treatment of renal diseases. PMID:9807019

  1. Investigating the Counteracting Effect of Trehalose on Urea-Induced Protein Denaturation Using Molecular Dynamics Simulation.

    PubMed

    Paul, Subrata; Paul, Sandip

    2015-08-27

    Molecular dynamics simulations are performed to investigate the counteracting effect of trehalose against urea-induced denaturation of S-peptide analogue. The calculations of Cα root-mean-square deviation, radius of gyration, and solvent-accessible surface area reveal that the peptide loses its native structure in aqueous 8 M urea solution at 310 K and that this unfolding process is prevented in the presence of trehalose. Interestingly, the native structure of the peptide in ternary mixed urea/trehalose solution is similar to that in the pure water system. The estimation of helical percentage of peptide residues as well as peptide-peptide intramolecular hydrogen bond number for different systems also support the above findings. Decomposition of protein-urea total interaction energy into electrostatic and van der Waals contributions shows that the presence of trehalose molecules makes the latter contribution unfavorable without affecting the former. These observations are further supported by preferential interaction calculations. Furthermore, the hydrogen bond analyses show that with the addition of urea molecules to the peptide-water system, the formation of peptide-urea hydrogen bonds takes place at the expense of peptide-water hydrogen bonds. In ternary mixed osmolytes system, because of formation of a considerable amount of peptide-trehalose hydrogen bonds, some urea molecules are excluded from the peptide surface. This essentially reduces the interaction between peptide and urea molecules, and because of this, we notice a reduction in the number of peptide-urea hydrogen bonds. Interestingly, the total number of peptide-solution species hydrogen bonds in the pure water system is very similar to that for the mixed osmolytes system. From these observations we infer that in the ternary solution, peptide-solution species hydrogen bonds are shared by water, urea, and trehalose molecules. The presence of trehalose in the mixed osmolyte system causes a significant

  2. Experimental and theoretical investigation of a pyridine containing Schiff base: Hirshfeld analysis of crystal structure, interaction with biomolecules and cytotoxicity

    NASA Astrophysics Data System (ADS)

    Chithiraikumar, S.; Neelakantan, M. A.

    2016-03-01

    A pyridine containing Schiff base (E)-2-methoxy-6-(((pyridin-2-ylmethyl)imino)methyl) phenol (L) was isolated in single crystals. The molecular structure of L was studied by FT-IR, NMR, UV-Vis techniques, single crystal XRD analysis and computationally by DFT method. L prefers enol form in the solid state. Electronic spectrum of L was recorded in different organic solvents to investigate the dependence of tautomerism on solvent types. The polar solvents facilitate the proton transfer by decreasing the activation energy needed for transition state. Potential energy curve for the intramolecular proton transfer in the ground state is generated in gas and solution phases. The 3D Hirshfeld surfaces and the associated 2D fingerprint plots were investigated. The percentages of various interactions were analyzed by fingerprint plots of Hirshfeld surface. The interaction of L with CT DNA was investigated under physiological conditions using UV-Vis spectroscopy, fluorescence quenching and molecular docking methods. Molecular docking studies reveal that binding of L to the groove of B-DNA is through hydrogen bonding and hydrophobic interactions. The in vitro cytotoxicity of L was carried out in two different human tumor cell lines, MCF 7 and MIA-Pa-Ca-2 exhibits moderate activity.

  3. Experimental and theoretical investigation of a pyridine containing Schiff base: Hirshfeld analysis of crystal structure, interaction with biomolecules and cytotoxicity

    NASA Astrophysics Data System (ADS)

    Chithiraikumar, S.; Neelakantan, M. A.

    2016-03-01

    A pyridine containing Schiff base (E)-2-methoxy-6-(((pyridin-2-ylmethyl)imino)methyl) phenol (L) was isolated in single crystals. The molecular structure of L was studied by FT-IR, NMR, UV-Vis techniques, single crystal XRD analysis and computationally by DFT method. L prefers enol form in the solid state. Electronic spectrum of L was recorded in different organic solvents to investigate the dependence of tautomerism on solvent types. The polar solvents facilitate the proton transfer by decreasing the activation energy needed for transition state. Potential energy curve for the intramolecular proton transfer in the ground state is generated in gas and solution phases. The 3D Hirshfeld surfaces and the associated 2D fingerprint plots were investigated. The percentages of various interactions were analyzed by fingerprint plots of Hirshfeld surface. The interaction of L with CT DNA was investigated under physiological conditions using UV-Vis spectroscopy, fluorescence quenching and molecular docking methods. Molecular docking studies reveal that binding of L to the groove of B-DNA is through hydrogen bonding and hydrophobic interactions. The in vitro cytotoxicity of L was carried out in two different human tumor cell lines, MCF 7 and MIA-Pa-Ca-2 exhibits moderate activity.

  4. Molecular dynamics simulations of formamide interaction with hydrocyanic acid on a catalytic surface TiO2

    NASA Astrophysics Data System (ADS)

    Artoshina, O. V.; Vorob'eva, M. Yu.; Dushanov, E. B.; Kholmurodov, Kh. T.

    2014-06-01

    The behavior of water—formamide and hydrocyanic acid—formamide solutions on an anatase surface have been studied using molecular dynamics (MD) simulation method. The interaction activation energies have been estimated for the temperature range from 250 up to 400 K. The diffusion coefficients and structural radial distribution functions have been calculated for the formamide, water and hydrocyanic acid on an anatase surface. The calculated activation energies of the water—formamide—anatase and hydrocyanic acid—formamide—anatase systems were analyzed and compared. A comparative analysis of the systems under investigation was performed and a possible correlation between the obtained MD results and the molecular mechanism involving the formamide's interaction with dioxide titan adsorbing surface were discussed.

  5. Molecular interactions between green tea catechins and cheese fat studied by solid-state nuclear magnetic resonance spectroscopy.

    PubMed

    Rashidinejad, Ali; Birch, Edward J; Hindmarsh, Jason; Everett, David W

    2017-01-15

    Molecular integrations between green tea catechins and milk fat globules in a cheese matrix were investigated using solid-state magic angle spinning nuclear magnetic resonance spectroscopy. Full-fat cheeses were manufactured containing free catechin or free green tea extract (GTE), and liposomal encapsulated catechin or liposomal encapsulated GTE. Molecular mobility of the carbon species in the cheeses was measured by a wide-line separation technique. The (1)H evolution frequency profile of the (13)C peak at 16ppm obtained for the control cheese and cheeses containing encapsulated polyphenols (catechin or GTE) were similar, however, the spectrum was narrower for cheeses containing free polyphenols. Differences in spectral width indicates changes in the molecular mobility of --CH3- or -C-C-PO4- species through hydrophobic and/or cation-π associations between green tea catechins and cheese fat components. However, the similar spectral profile suggests that encapsulation protects cheese fat from interaction with catechins.

  6. Molecular interactions between green tea catechins and cheese fat studied by solid-state nuclear magnetic resonance spectroscopy.

    PubMed

    Rashidinejad, Ali; Birch, Edward J; Hindmarsh, Jason; Everett, David W

    2017-01-15

    Molecular integrations between green tea catechins and milk fat globules in a cheese matrix were investigated using solid-state magic angle spinning nuclear magnetic resonance spectroscopy. Full-fat cheeses were manufactured containing free catechin or free green tea extract (GTE), and liposomal encapsulated catechin or liposomal encapsulated GTE. Molecular mobility of the carbon species in the cheeses was measured by a wide-line separation technique. The (1)H evolution frequency profile of the (13)C peak at 16ppm obtained for the control cheese and cheeses containing encapsulated polyphenols (catechin or GTE) were similar, however, the spectrum was narrower for cheeses containing free polyphenols. Differences in spectral width indicates changes in the molecular mobility of --CH3- or -C-C-PO4- species through hydrophobic and/or cation-π associations between green tea catechins and cheese fat components. However, the similar spectral profile suggests that encapsulation protects cheese fat from interaction with catechins. PMID:27542471

  7. Antisense molecular beacon strategy for in situ visualization of snRNA and fibrillarin protein interaction in Giardia lamblia.

    PubMed

    Ganguly, Sandipan; Ghosh, Srikanta; Chattopadhyay, Dhrubajyoti; Das, Pradeep

    2004-05-01

    Use of confocal microscopy has provided many recent developments in the study of functional aspects, especially localization and distribution of proteins, DNA and RNA within the cells. In the present investigation, we have applied for the first time, antisense molecular beacon based Fluorescence Resonance Energy Transfer (FRET) and Flow Cytometric Energy Transfer (FCET) techniques to demonstrate binding and co-localization of fibrillarin protein with small nuclear RNA (snRNA) to form ribonucleoprotein particle (RNPP) complex in Giardia lamblia. It has been observed by FRET and FCET that energy transfer occurs from fluorescence tagged fibrillarin to snRNA antisense molecular beacon confirming the clear physical interaction between them during RNPP complex formation. This is the first demonstration of in situ detection of RNA-protein complex formation by antisense molecular beacon based FRET and FCET in Giardia lamblia.

  8. Interaction of the Disaccharide Trehalose with a Phospholipid Bilayer: A Molecular Dynamics Study

    PubMed Central

    Pereira, Cristina S.; Lins, Roberto D.; Chandrasekhar, Indira; Freitas, Luiz Carlos G.; Hünenberger, Philippe H.

    2004-01-01

    The disaccharide trehalose is well known for its bioprotective properties. Produced in large amounts during stress periods in the life of organisms able to survive potentially damaging conditions, trehalose plays its protective role by stabilizing biostructures such as proteins and lipid membranes. In this study, molecular dynamics simulations are used to investigate the interaction of trehalose with a phospholipid bilayer at atomistic resolution. Simulations of the bilayer in the absence and in the presence of trehalose at two different concentrations (1 or 2 molal) are carried out at 325 K and 475 K. The results show that trehalose is able to minimize the disruptive effect of the elevated temperature and stabilize the bilayer structure. At both temperature, trehalose is found to interact directly with the bilayer through hydrogen bonds. However, the water molecules at the bilayer surface are not completely replaced. At high temperature, the protective effect of trehalose is correlated with a significant increase in the number of trehalose-bilayer hydrogen bonds, predominantly through an increase in the number of trehalose molecules bridging three or more lipid molecules. PMID:15041666

  9. Molecular aspects on the interaction of phenosafranine to deoxyribonucleic acid: Model for intercalative drug DNA binding

    NASA Astrophysics Data System (ADS)

    Das, Suman; Kumar, Gopinatha Suresh

    2008-01-01

    The mode, mechanism and energetics of interaction of phenosafranine, the planar, cationic and rigid phenazium dye to calf thymus DNA was investigated from absorption, fluorescence, circular dichroism, isothermal titration calorimetry, thermal melting, and viscosity. The study revealed non-cooperative binding of the dye to DNA with an affinity in the range (3.81-4.22) × 10 5 M -1 as observed from diverse techniques and obeying neighbor exclusion principle. The stoichiometry of binding was characterized to be one phenosafranine molecule per two base pairs. The binding was characterized by strong stabilization of DNA against thermal strand separation, large intrinsic circular dichroic changes of DNA by itself and the generation of induced circular dichroism for the optically inactive phenosafranine molecules. Hydrodynamic and fluorescence quenching studies revealed strong evidence that the phenosafranine molecules are intercalated between every alternate base pairs of calf thymus DNA. Isothermal titration calorimetry studies suggested that the binding was exothermic and favoured by both negative enthalpy and positive entropy changes. This study for the first time presents the complete molecular aspects and energetics of phenosafranine complexation to DNA as model for intercalative drug-DNA interaction.

  10. Molecular interactions of exogenous chemical agents with collagen—implications for tissue optical clearing

    NASA Astrophysics Data System (ADS)

    Yeh, Alvin T.; Hirshburg, Jason

    2006-01-01

    Reduction of optical scattering in turbid biological tissues using nonreactive chemical agents has potential applications for light-based diagnostics and therapeutics. Optical clearing effects by exogenous chemical agents, in particular sugars and sugar alcohols, have been found to be temporary with tissue rehydration. Applications with dermatologic laser therapies are now being investigated, but suffer from the inability of studied agents to penetrate the superficial layers of human skin. Selection, design, and refinement of topically effective chemical agents are hindered by a lack of fundamental understanding of tissue clearing mechanisms. We present recent work, particularly from the biochemistry community, detailing molecular interactions between chemical agents and collagen. This body of work demonstrates the perturbative effects of sugars and sugar alcohols on collagen high-order structures at micro- and nanometer length scales by screening noncovalent bonding forces. In addition, these studies emphasize the nonreactive nature of agent-collagen interactions and the ability of noncovalent bonding forces to recover with agent removal and drive reassembly of destabilized collagen structures. A mechanism of tissue optical clearing is proposed based on agent destabilization of high-order collagen structures.

  11. Investigation of Nanoscale Interactions by Means of Subharmonic Excitation.

    PubMed

    Chiesa, Matteo; Gadelrab, Karim; Stefancich, Marco; Armstrong, Peter; Li, Guang; Souier, Tewfik; Thomson, Neil H; Barcons, Victor; Font, Josep; Verdaguer, Albert; Phillips, Michael A; Santos, Sergio

    2012-08-16

    Multifrequency atomic force microscopy holds promise as a method to provide qualitative and quantitative information about samples with high spatial resolution. Here, we provide experimental evidence of the excitation of subharmonics in ambient conditions in the regions where capillary interactions are predicted to be the mechanism of excitation. We also experimentally decouple a second mechanism for subharmonic excitation that is highly independent of environmental conditions such as relative humidity. This implies that material properties could be mapped. Subharmonic excitation could lead to experimental determination of surface water affinity in the nanoscale whenever water interactions are the mechanism of excitation.

  12. Investigating the molecular and aggregated states of a drug molecule rutaecarpine using spectroscopy, microscopy, crystallography and computational studies.

    PubMed

    Dandpat, Shiba Sundar; Sarkar, Moloy

    2015-06-01

    The photophysical properties of a potential drug molecule rutaecarpine have been investigated in molecular as well as aggregated states. All systems have been characterized by various spectroscopic, microscopic and dynamic light scattering (DLS) techniques. The investigation has been carried out by keeping the fact in mind that hydrophobic organic molecules have a strong tendency to form aggregates in aqueous solution. A blue shift in the absorption spectrum of rutaecarpine has been observed for aggregates (compared to molecular solution) indicating the formation of H-type aggregates. The intermolecular interactions responsible for such aggregation have been further investigated through crystallographic and computational studies. It has been observed that π-π stacking interactions among the monomer units play an important role in the formation of H-type aggregates. Quantum mechanical calculations also substantiate the blue shift in the absorption that has been observed for aggregates. In the present case, enhanced emission for aggregates as compared to the molecular solution of rutaecarpine has also been observed. The observed enhanced emission upon aggregation is attributed to the decrease of the non-radiative rate constant (knr) upon aggregation. The effect of a surface active ionic liquid (SAIL), 1-dodecyl-3-methylimidazolium bromide ([C12mim]Br), on the aggregation of rutaecarpine has been investigated. Interestingly, in addition to the decrease in the particle size, a change in the morphology of the aggregates has also been observed with gradual addition of [C12mim]Br to the colloidal solution of rutaecarpine. The present study demonstrates that a SAIL can effectively be used as a medium for dissociation of colloidal aggregates and encapsulation of molecular species, which in turn would be helpful in influencing the drug activity. PMID:25948504

  13. [Interaction between ambroxol hydrochloride and human serum albumin studied by spectroscopic and molecular modeling methods].

    PubMed

    Liang, Jing; Feng, Su-Ling

    2011-04-01

    In the present paper, the interaction between ambroxol hydrochloride (ABX) and human serum albumin (HSA) was studied under simulative physiological condition by spectroscopy and molecular modeling method. Stern-Volmer curvers at different temperatures and UV-Vis absorption spectroscopy showed that ABX quenched the fluorescence of HSA mainly through dynamic quenching mode. On the basis of the thermodynamic data, the main binding force between them is hydrophobic interaction. According to the theory of Forster non-radiation energy transfer, the binding distance between the donor and the acceptor was 3.01 nm. The effect of ABX on the conformation of HSA was analyzed by the synchronous and three-dimensional fluorescence spectroscopy. Furthermore, using the molecular modeling method, the interaction between them was predicted from molecular angle: ABX might locate in the subdomain III A of HSA. PMID:21714251

  14. Protozoan HSP90-heterocomplex: molecular interaction network and biological significance.

    PubMed

    Figueras, Maria J; Echeverria, Pablo C; Angel, Sergio O

    2014-05-01

    The HSP90 chaperone is a highly conserved protein from bacteria to higher eukaryotes. In eukaryotes, this chaperone participates in different large complexes, such as the HSP90 heterocomplex, which has important biological roles in cell homeostasis and differentiation. The HSP90-heterocomplex is also named the HSP90/HSP70 cycle because different co-chaperones (HIP, HSP40, HOP, p23, AHA1, immunophilins, PP5) participate in this complex by assembling sequentially, from the early to the mature complex. In this review, we analyze the conservation and relevance of HSP90 and the HSP90-heterocomplex in several protozoan parasites, with emphasis in Plasmodium spp., Toxoplasma spp., Leishmania spp. and Trypanosoma spp. In the last years, there has been an outburst of studies based on yeast two-hybrid methodology, co-immunoprecipitation-mass spectrometry and bioinformatics, which have generated a most comprehensive protein-protein interaction (PPI) network of HSP90 and its co-chaperones. This review analyzes the existing PPI networks of HSP90 and its co-chaperones of some protozoan parasites and discusses the usefulness of these powerful tools to analyze the biological role of the HSP90-heterocomplex in these parasites. The generation of a T. gondii HSP90 heterocomplex PPI network based on experimental data and a recent Plasmodium HSP90 heterocomplex PPI network are also included and discussed. As an example, the putative implication of nuclear transport and chromatin (histones and Sir2) as HSP90-heterocomplex interactors is here discussed.

  15. Protozoan HSP90-heterocomplex: molecular interaction network and biological significance.

    PubMed

    Figueras, Maria J; Echeverria, Pablo C; Angel, Sergio O

    2014-05-01

    The HSP90 chaperone is a highly conserved protein from bacteria to higher eukaryotes. In eukaryotes, this chaperone participates in different large complexes, such as the HSP90 heterocomplex, which has important biological roles in cell homeostasis and differentiation. The HSP90-heterocomplex is also named the HSP90/HSP70 cycle because different co-chaperones (HIP, HSP40, HOP, p23, AHA1, immunophilins, PP5) participate in this complex by assembling sequentially, from the early to the mature complex. In this review, we analyze the conservation and relevance of HSP90 and the HSP90-heterocomplex in several protozoan parasites, with emphasis in Plasmodium spp., Toxoplasma spp., Leishmania spp. and Trypanosoma spp. In the last years, there has been an outburst of studies based on yeast two-hybrid methodology, co-immunoprecipitation-mass spectrometry and bioinformatics, which have generated a most comprehensive protein-protein interaction (PPI) network of HSP90 and its co-chaperones. This review analyzes the existing PPI networks of HSP90 and its co-chaperones of some protozoan parasites and discusses the usefulness of these powerful tools to analyze the biological role of the HSP90-heterocomplex in these parasites. The generation of a T. gondii HSP90 heterocomplex PPI network based on experimental data and a recent Plasmodium HSP90 heterocomplex PPI network are also included and discussed. As an example, the putative implication of nuclear transport and chromatin (histones and Sir2) as HSP90-heterocomplex interactors is here discussed. PMID:24694366

  16. Noninvasive Molecular Fingerprinting of Host Microbiome Interactions in Neonates

    PubMed Central

    Donovan, Sharon M.; Wang, Mei; Monaco, Marcia H.; Martin, Camilia R.; Davidson, Laurie A.; Ivanov, Ivan; Chapkin, Robert S.

    2014-01-01

    The early postnatal period is a critical window for intestinal and immune maturation. Intestinal development and microbiome diversity and composition differ between breast- (BF) and formula-fed (FF) infants. Mechanistic examination into host-microbe relationships in healthy infants has been hindered by ethical constraints surrounding tissue biopsies. Thus, a statistically rigorous analytical framework to simultaneously examine both host and microbial responses to dietary/environmental factors using exfoliated intestinal epithelial cells was developed. Differential expression of ~1,200 genes, including genes regulating intestinal proliferation, differentiation and barrier function, was observed between BF and FF term infants. Canonical correlation analysis uncovered a relationship between microbiome virulence genes and host immunity and defense genes. Lastly, exfoliated cells from preterm and term infants were compared. Pathways associated with immune cell function and inflammation were up-regulated in preterm, whereas cell growth-related genes were up-regulated in the term infants. Thus, coordinate measurement of the transcriptomes of exfoliated epithelial cells and microbiome allows inquiry into mutualistic host-microbe interactions in the infant, which can be used to prospectively study gut development or, retrospectively, to identify potential triggers of disease in banked samples. PMID:25042036

  17. Advances in the molecular understanding of gonadotropins-receptors interactions.

    PubMed

    el Tayar, N

    1996-12-20

    The extracellular domain (ECD) of gonadotropin receptors belong to the leucine-rich repeat (LRR) protein superfamily and their transmembrane domain (TMD) is characteristic of the seven alpha-helices G-protein-coupled receptors (GPCR). The availability of the X-ray structures of porcine ribonuclease inhibitor (RI), a LRR protein, and bacteriorhodopsin (bR) allows the construction of 3D models of the ECD and the TMD of gonadotropin receptors, respectively. The predicted models are to a large extent consistent with currently available biochemical and mutational data. The models provide a reliable basis for understanding how the hormone binds and activates its receptor. The ECD, in particular the LRR region, serves as a baseball glove which efficiently catches the large hormone and optimally orient the appropriate parts of it for interaction with the seven-transmembrane-helix domain of the receptor. This in turn is expected to lead to a conformational change to be sensed by the appropriate G-protein complex leading to the stimulation of cAMP synthesis and steroids production.

  18. Molecular properties of cetiedil and its interactions with human erythrocytes

    SciTech Connect

    Narasimhan, C.

    1987-01-01

    Cetiedil, an antisickling agent and a vascular smooth muscle relaxant is an amphiphilic molecule. Our studies show that the molecule in the citrate salt form is highly acidic at millimolar concentrations. The critical micelle concentration in 5 mM phosphate buffer with 150 mM NaCl is about 8.8 mM. The UV absorption extinction coefficient at 233 nm, E/sub 233/, is 2796 M/sup -1/ cm/sup -1/. Conformational studies of cetiedil using /sup 13/C NMR spectroscopy showed that the cyclohexyl moiety of cetiedil is in the chair conformation and the molecule undergoes an overall conformational change as the solvent polarity and ionic strength change. /sup 1/H NMR experiments of cetiedil at different concentrations showed that, cetiedil at concentrations greater than 7 mM may form pre-micelle aggregates. Both /sup 13/C and /sup 1/H NMR data of cetiedil in the presence of membranes showed that the nonpolar region of the molecule are affected more upon interacting with the membranes than the polar region.

  19. Cellular regulation and molecular interactions of the ferritins.

    PubMed

    Hintze, K J; Theil, E C

    2006-03-01

    Controlling iron/oxygen chemistry in biology depends on multiple genes, regulatory messenger RNA (mRNA) structures, signaling pathways and protein catalysts. Ferritin, a protein nanocage around an iron/oxy mineral, centralizes the control. Complementary DNA (antioxidant responsive element/Maf recognition element) and mRNA (iron responsive element) responses regulate ferritin synthesis rates. Multiple iron-protein interactions control iron and oxygen substrate movement through the protein cage, from dynamic gated pores to catalytic sites related to di-iron oxygenase cofactor sites. Maxi-ferritins concentrate iron for the bio-synthesis of iron/heme proteins, trapping oxygen; bacterial mini-ferritins, DNA protection during starvation proteins, reverse the substrate roles, destroying oxidants, trapping iron and protecting DNA. Ferritin is nature's unique and conserved approach to controlled, safe use of iron and oxygen, with protein synthesis in animals adjusted by dual, genetic DNA and mRNA sequences that selectively respond to iron or oxidant signals and link ferritin to proteins of iron, oxygen and antioxidant metabolism.

  20. Molecular-scale hydrophobic interactions between hard-sphere reference solutes are attractive and endothermic

    PubMed Central

    Chaudhari, Mangesh I.; Holleran, Sinead A.; Ashbaugh, Henry S.; Pratt, Lawrence R.

    2013-01-01

    The osmotic second virial coefficients, B2, for atomic-sized hard spheres in water are attractive (B2 < 0) and become more attractive with increasing temperature (ΔB2/ΔT < 0) in the temperature range 300 K ≤ T ≤ 360 K. Thus, these hydrophobic interactions are attractive and endothermic at moderate temperatures. Hydrophobic interactions between atomic-sized hard spheres in water are more attractive than predicted by the available statistical mechanical theory. These results constitute an initial step toward detailed molecular theory of additional intermolecular interaction features, specifically, attractive interactions associated with hydrophobic solutes. PMID:24297918

  1. Housing helpful invaders: the evolutionary and molecular architecture underlying plant root-mutualist microbe interactions.

    PubMed

    Lagunas, B; Schäfer, P; Gifford, M L

    2015-04-01

    Plant root rhizosphere interactions with mutualistic microbes are diverse and numerous, having evolved over time in response to selective pressures on plants to attain anchorage and nutrients. These relationships can be considered to be formed through a combination of architectural connections: molecular architecture interactions that control root-microbe perception and regulate the balance between host and symbiont and developmental architecture interactions that enable the microbes to be 'housed' in the root and enable the exchange of compounds. Recent findings that help to understand the common architecture that exists between nodulation and mycorrhizal interactions, and how this architecture could be re-tuned to develop new symbioses, are discussed here.

  2. Counterpoise-corrected interaction energy analysis based on the fragment molecular orbital scheme

    NASA Astrophysics Data System (ADS)

    Okiyama, Yoshio; Fukuzawa, Kaori; Yamada, Haruka; Mochizuki, Yuji; Nakano, Tatsuya; Tanaka, Shigenori

    2011-06-01

    Basis set superposition error (BSSE) correction with counterpoise (CP) procedure under the environmental electrostatic potential is newly introduced to interfragment interaction energy (IFIE), which is important for interaction analysis in the fragment molecular orbital method. The CP correction for IFIE is applied to a stacked dimer of base pair and a protein-ligand complex of estrogen receptor and 17β-estradiol with scaled third-order Møller-Plesset perturbation theory. The BSSEs amount to about quarter of IFIE for hydrogen-bonding and electrostatic interactions and half or even more for dispersion interactions. Estimation of IFIE with the CP correction is therefore preferred for the quantitative discussion.

  3. Small-angle X-ray scattering method to characterize molecular interactions: Proof of concept.

    PubMed

    Allec, Nicholas; Choi, Mina; Yesupriya, Nikhil; Szychowski, Brian; White, Michael R; Kann, Maricel G; Garcin, Elsa D; Daniel, Marie-Christine; Badano, Aldo

    2015-01-01

    Characterizing biomolecular interactions is crucial to the understanding of biological processes. Existing characterization methods have low spatial resolution, poor specificity, and some lack the capability for deep tissue imaging. We describe a novel technique that relies on small-angle X-ray scattering signatures from high-contrast molecular probes that correlate with the presence of biomolecular interactions. We describe a proof-of-concept study that uses a model system consisting of mixtures of monomer solutions of gold nanoparticles (GNPs) as the non-interacting species and solutions of GNP dimers linked with an organic molecule (dimethyl suberimidate) as the interacting species. We report estimates of the interaction fraction obtained with the proposed small-angle X-ray scattering characterization method exhibiting strong correlation with the known relative concentration of interacting and non-interacting species. PMID:26160052

  4. Interaction Between Molecular Iodine in a Gas Phase and Paints Aged in a Nuclear Power Plant

    SciTech Connect

    Zoulalian, Andre; Belval-Haltier, Edith

    2000-06-15

    The interactions of gaseous molecular iodine with painted surfaces aged in French nuclear pressurized water reactors (PWRs) were carried out in an experimental facility consisting of a molecular iodine generator, a mixing chamber, a sampling chamber, a specimen holder, and a gamma-counting probe [Cristal NaI(Tl)]. The same experimental facility was used to precisely measure the gaseous molecular iodine interactions with epoxy-painted coupons conditioned by two artificial hydrothermal treatments, either by heating at 130degC in a dry atmosphere or by heating at 130 deg. C in a saturated water atmosphere. Then, a kinetic model was developed to represent these experimental results.This paper examines if the previous kinetic model can be used to interpret the gaseous molecular iodine interactions with aged paints. With the rate constant values found for the artificially conditioned paints, the kinetic model agrees with experimental results. Moreover, for the three studied temperatures (95, 110, and 125 deg. C), the values of initial adsorbed water concentration onto the paint and the adsorbed water concentration in equilibrium with the steam of the carrier gas are intermediate between the values found for the two artificial hydrothermal treatments.Finally, a kinetic model is available, allowing the evaluation of precise assessments of the gaseous molecular iodine interactions with aged epoxy paints in the case of a severe PWR accident.

  5. Infrared Spectroscopy of Transition Metal-Molecular interactions in the Gas Phase

    SciTech Connect

    Duncan, Michael A.

    2008-11-14

    Transition metal-molecular complexes produced in a molecular beam are mass-selected and studied with infrared laser photodissociation spectroscopy. Metal complexes with carbon monoxide, carbon dioxide, nitrogen, water, acetylene or benzene are studied for a variety of metals. The number and intensity of infrared active bands are compared to the predictions of density functional theory calculations to derive structures, spin states and coordination numbers in these systems. These studied provide new insights into subtle details of metal-molecular interactions important in heterogeneous catalysis, metal-ligand bonding and metal ion solvation.

  6. Investigation of the In-Medium Kaon-Nucleon Interaction

    NASA Astrophysics Data System (ADS)

    Wood, Michael; CLAS Collaboration

    2013-10-01

    One method to study the strong interaction inside of the nucleus is with the absorption of hadrons. The E01-112 experiment in Hall B at the Thomas Jefferson National Accelerator provided data on the photo-production of the Ks0 in nuclei of deuterium, carbon, iron, and lead. The kaon is interesting since the antikaon-nucleon potential is attractive, leading to predictions of strangeness in a dense environment like a neutron star. On the other hand, the kaon-nucleon potential is repulsive, indicating that kaons should traverse the medium with fewer interactions. The absorption of the Ks0 by a bound nucleon inside a nucleus will indicate how the potential changes; is it strengthened or weakened in the medium. In this talk, I will present preliminary transparency ratios versus mass number.

  7. Interaction of meropenem with 'N' and 'B' isoforms of human serum albumin: a spectroscopic and molecular docking study.

    PubMed

    Rehman, Md Tabish; Ahmed, Sarfraz; Khan, Asad U

    2016-09-01

    Carbapenems are used to control the outbreak of β-lactamases expressing bacteria. The effectiveness of drugs is influenced by its interaction with human serum albumin (HSA). Strong binding of carbapenems to HSA may lead to decreased bioavailability of the drug. The non-optimal drug dosage will provide a positive selection pressure on bacteria to develop resistance. Here, we investigated the interaction between meropenem and HSA at physiological pH 7.5 (N-isoform HSA) and non-physiological pH 9.2 (B-isoform HSA). Results showed that meropenem quenches the fluorescence of both 'N' and 'B' isoforms of HSA (ΔG < 0 and binding constant ~10(4) M(-1)). Electrostatic interactions and van der Waal interactions along with H-bonds stabilized the complex of meropenem with 'N' and 'B' isoforms of HSA, respectively. Molecular docking results revealed that meropenem binds to HSA near Sudlow's site II (subdomain IIIA) close to Trp-214 with a contribution of a few residues of subdomain IIA. CD spectroscopy showed a change in the conformation of both the isoforms of HSA upon meropenem binding. The catalytic efficiency of HSA (only N-isoform) on p-nitrophenyl acetate was increased primarily due to a decrease in Km and an increase in kcat values. This study provides an insight into the molecular basis of interaction between meropenem and HSA.

  8. Molecular interactions of ribosomal components. IV: Cooperative interactions during assembly in vitro.

    PubMed

    Green, M; Kurland, C G

    1973-08-01

    Cooperative interactions between different 30S ribosomal proteins during assembly in vitro are described. The site specific binding of S7 to 16S RNA is enhanced by S20; that of S16 requires S4 and S20; and S7 is required for the maximum binding of S9, S13 and S19. Some of these interactions are reflected in the protein neighborhoods of the functional ribosome, but this may not be a general rule. Finally, we suggest that the assembly cooperativety observed may not be a consequence of direct-protein interactions.

  9. Investigating Mixture Interactions of Astringent Stimuli Using the Isobole Approach.

    PubMed

    Fleming, Erin E; Ziegler, Gregory R; Hayes, John E

    2016-09-01

    Astringents (alum, malic acid, tannic acid) representing 3 broad classes (multivalent salts, organic acids, and polyphenols) were characterized alone, and as 2- and 3-component mixtures using isoboles. In experiment 1, participants rated 7 attributes ("astringency," the sub-qualities "drying," "roughing," and "puckering," and the side tastes "bitterness," "sourness," and "sweetness") using direct scaling. Quality specific power functions were calculated for each stimulus. In experiment 2, the same participants characterized 2- and 3-component mixtures. Multiple factor analysis (MFA) and hierarchical clustering on attribute ratings across stimuli indicate "astringency" is highly related to "bitterness" as well as "puckering," and the subqualities "drying" and "roughing" are somewhat redundant. Moreover, power functions were used to calculate indices of interaction (I) for each attribute/mixture combination. For "astringency," there was evidence of antagonism, regardless of the type of mixture. Conversely, for subqualities, the pattern of interaction depended on the mixture type. Alum/tannic acid and tannic acid/malic acid mixtures showed evidence of synergy for "drying" and "roughing"; alum/malic acid mixtures showed evidence of antagonism for "drying," "roughing," and "puckering." Collectively, these data clarify some semantic ambiguity regarding astringency and its subqualities, as well as the nature of interactions of among different types of astringents. Present data are not inconsistent with the idea that astringency arises from multiple mechanisms, although it remains to be determined whether the synergy observed here might reflect simultaneous activation of these multiple mechanisms. PMID:27252355

  10. Numerical investigation of acoustic radiation from vortex-airfoil interaction

    NASA Astrophysics Data System (ADS)

    Legault, Anne; Ji, Minsuk; Wang, Meng

    2012-11-01

    Numerical simulations of vortices interacting with a NACA 0012 airfoil and a flat-plate airfoil at zero angle of attack are carried out to assess the applicability and accuracy of classical theories. Unsteady lift and sound are computed and compared with the predictions by theories of Sears and Amiet, which assume a thin-plate airfoil in an inviscid flow. A Navier-Stokes solver is used in the simulations, and therefore viscous effects are taken into consideration. For the thin-plate airfoil, the effect of viscosity is negligible. For a NACA 0012 airfoil, the viscous contribution to the unsteady lift and sound mainly comes from coherent vortex shedding in the wake of the airfoil and the interaction of the incoming vortices with the airfoil wake, which become stronger at higher Reynolds numbers for a 2-D laminar flow. When the flow is turbulent at chord Reynolds number of 4 . 8 ×105 , however, the viscous contribution becomes negligible as coherent vortex shedding is not present. Sound radiation from vortex-airfoil interaction at turbulent Reynolds numbers is computed numerically via Lighthill's theory and the result is compared with the predictions of Amiet and Curle. The effect of the airfoil thickness is also examined. Supported by ONR Grant N00014-09-1-1088.

  11. DyNet: visualization and analysis of dynamic molecular interaction networks

    PubMed Central

    Goenawan, Ivan H.; Lynn, David J.

    2016-01-01

    Summary: The ability to experimentally determine molecular interactions on an almost proteome-wide scale under different conditions is enabling researchers to move from static to dynamic network analysis, uncovering new insights into how interaction networks are physically rewired in response to different stimuli and in disease. Dynamic interaction data presents a special challenge in network biology. Here, we present DyNet, a Cytoscape application that provides a range of functionalities for the visualization, real-time synchronization and analysis of large multi-state dynamic molecular interaction networks enabling users to quickly identify and analyze the most ‘rewired’ nodes across many network states. Availability and Implementation: DyNet is available at the Cytoscape (3.2+) App Store (http://apps.cytoscape.org/apps/dynet). Contact: david.lynn@sahmri.com. Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:27153624

  12. 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.

  13. Effects of water concentration on the free volume of amino acid ionic liquids investigated by molecular dynamics simulations.

    PubMed

    Shaikh, Abdul Rajjak; Kamio, Eiji; Takaba, Hiromitsu; Matsuyama, Hideto

    2015-01-01

    Amino acid ionic liquids (AAILs) are gaining attention because of their potential in CO2 capture technology. Molecular dynamics simulations of AAILs tetramethylammonium glycinate ([N1111][Gly]), tetrabutylammonium glycinate ([N4444][Gly]), and 1,1,1-trimethylhydrazinium glycinate ([aN111][Gly]) and their corresponding mixtures with water were performed to investigate the effect of water concentration on the cation-anion interactions. The water content significantly influenced the free volume (FV) and fractional free volume (FFV) of the AAILs that varied with the hydrophobic and hydrophilic nature of the ion pairs. Under dry conditions, the FFV increased with increasing cation molecular sizes, indicative of proportional adsorption of any inert gases, such as N2, as consistent with experimental observations. Furthermore, the polarity of the cation played an important role in FFV and hence the diffusion of the AAILs. Density functional theory calculations suggested that hydrophilic [aN111][Gly] featured stronger interactions in the presence of water, whereas the hydrophobic IL showed weaker interactions. The carboxylate group of glycinate displayed stronger interactions with water than the cation. The computational study provided qualitative insight into the role of FV of the AAILs on CO2 and N2 absorption and suggests that [aN111][Gly] has CO2 adsorption capacity in the presence of water superior to that of other studied AAILs.

  14. A Computational Study of the Interaction and Polarization Effects of Complexes Involving Molecular Graphene and C60 or a Nucleobases.

    PubMed

    Avramopoulos, Aggelos; Otero, Nicolás; Karamanis, Panaghiotis; Pouchan, Claude; Papadopoulos, Manthos G

    2016-01-21

    A systematic analysis of the molecular structure, energetics, electronic (hyper)polarizabilities and their interaction-induced counterparts of C60 with a series of molecular graphene (MG) models, CmHn, where m = 24, 84, 114, 222, 366, 546 and n = 12, 24, 30, 42, 54, 66, was performed. All the reported data were computed by employing density functional theory and a series of basis sets. The main goal of the study is to investigate how alteration of the size of the MG model affects the strength of the interaction, charge rearrangement, and polarization and interaction-induced polarization of the complex, C60-MG. A Hirshfeld-based scheme has been employed in order to provide information on the intrinsic polarizability density representations of the reported complexes. It was found that the interaction energy increases approaching a limit of -26.98 kcal/mol for m = 366 and 546; the polarizability and second hyperpolarizability increase with increasing the size of MG. An opposite trend was observed for the dipole moment. Interestingly, the variation of the first hyperpolarizability is relatively small with m. Since polarizability is a key factor for the stability of molecular graphene with nucleobases (NB), a study of the magnitude of the interaction-induced polarizability of C84H24-NB complexes is also reported, aiming to reveal changes of its magnitude with the type of NB. The binding strength of C84H24-NB complexes is also computed and found to be in agreement with available theoretical and experimental data. The interaction involved in C60 B12N12H24-NB complexes has also been considered, featuring the effect of contamination on the binding strength between MG and NBs.

  15. Armchair BN nanotubes--levothyroxine interactions: a molecular study.

    PubMed

    Anota, E Chigo; Cocoletzi, Gregorio H; Ramírez, J F Sánchez

    2013-11-01

    The density functional theory has been applied to investigate the structural and electronic properties of single-wall boron nitride nanotubes (SW-BNNT) of (5,5) chirality, with surface and ends functionalized by the drug levothyroxine (C15H11NI4O4). The exchange-correlation energies have been modeled according to the Hamprecht-Cohen-Tozer-Handy functional within the generalized gradient approximation (HCTH-GGA) and a base function with double polarization has been used. The (5,5) BNNT-Levothyroxine structural optimization has been done considering the minimum energy criterion in nine possible atomic structures. Simulation results indicate that the preferential adsorption site (chemical adsorption) of the levothyroxine fragment is at the nanotube ends. The BNNT-Levothyroxine system polarity increases which indicates the possible dispersion and solubility both non-solvated and solvated in water. The BNNT-Levothyroxine solvated in water modifies its chemical reactivity which may allow the drug delivery within the biological systems. On the other hand, the decrease in the work function is important for the optoelectronic device design, which also makes these materials suitable to improve the field emission properties. PMID:24068307

  16. Investigating Conversational Dynamics: Interactive Alignment, Interpersonal Synergy, and Collective Task Performance

    ERIC Educational Resources Information Center

    Fusaroli, Riccardo; Tylén, Kristian

    2016-01-01

    This study investigates interpersonal processes underlying dialog by comparing two approaches, "interactive alignment" and "interpersonal synergy", and assesses how they predict collective performance in a joint task. While the interactive alignment approach highlights imitative patterns between interlocutors, the synergy…

  17. Liquid crystals and their interactions with colloidal particles and phospholipid membranes: Molecular simulation studies

    NASA Astrophysics Data System (ADS)

    Kim, Evelina B.

    Experimentally, liquid crystals (LC) can be used as the basis for optical biomolecular sensors that rely on LC ordering. Recently, the use of LC as a reporting medium has been extended to investigations of molecular scale processes at lipid laden aqueous-LC interfaces and at biological cell membranes. In this thesis, we present two related studies where liquid crystals are modelled at different length scales. We examine (a) the behavior of nanoscopic colloidal particles in LC systems, using Monte Carlo (MC) molecular simulations and a mesoscopic dynamic field theory (DyFT); and (b) specific interactions of two types of mesogens with a model phospholipid bilayer, using atomistic molecular dynamics (MD) at the A-nm scale. In (a), we consider colloidal particles suspended in a LC, confined between two walls. We calculate the colloid-substrate and colloid-colloid potentials of mean force (PMF). For the MC simulations, we developed a new technique (ExEDOS or Expanded Ensemble Density Of States) that ensures good sampling of phase space without prior knowledge of the energy landscape of the system. Both results, simulation and DyFT, indicate a repulsive force acting between a colloid and a wall. In contrast, both techniques indicate an overall colloid-colloid attraction and predict a new topology of the disclination lines that arises when the particles approach each other. In (b), we find that mesogens (pentylcyanobiphenyl [5CB] or difluorophenyl-pentylbicyclohexyl [5CF]) preferentially partition from the aqueous phase into a dipalmitoylphosphatidylcholine (DPPC) bilayer. We find highly favorable free energy differences for partitioning (-18kBT for 5CB, -26k BT for 5CF). We also simulated fully hydrated bilayers with embedded 5CB or 5CF at concentrations used in recent experiments (6 mol% and 20 mol%). The presence of mesogens in the bilayer enhances the order of lipid acyl tails and changes the spatial and orientational arrangement of lipid headgroup atoms. A stronger

  18. Effects of wettability and interfacial nanobubbles on flow through structured nanochannels: an investigation of molecular dynamics

    NASA Astrophysics Data System (ADS)

    Yen, Tsu-Hsu

    2015-12-01

    Solid-fluid boundary conditions are strongly influenced by a number of factors, including the intrinsic properties of the solid/fluid materials, surface roughness, wettability, and the presence of interfacial nanobubbles (INBs). The interconnected nature of these factors means that they should be considered jointly. This paper employs molecular dynamics (MD) simulation in a series of studies aimed at elucidating the influence of wettability in boundary behaviour and the accumulation of interfacial gas. Specifically, we examined the relationship between effective slip length, the morphology of nanobubbles, and wettability. Two methods were employed for the promotion of hydrophobicity between two structured substrates with similar intrinsic contact angles. We also compared anisotropic and isotropic atomic arrangements in the form of graphite and Si(100), respectively. A physical method was employed to deal with variations in surface roughness, whereas a chemical method was used to adjust the wall-fluid interaction energy (ɛwf). We first compared the characteristic properties of wettability, including contact angle and fluid density within the cavity. We then investigated the means by which variations in solid-fluid interfacial wettability affect interfacial gas molecules. Our results reveal that the morphology of INB on a patterned substrate is determined by wettability as well as the methods employed for the promotion of hydrophobicity. The present study also illustrates the means by which the multiple effects of the atomic arrangement of solids, surface roughness, wettability and INB influence effective slip length.

  19. Mechanistic investigations and molecular medicine applications of gold nanoparticle mediated (GNOME) laser transfection

    NASA Astrophysics Data System (ADS)

    Schomaker, M.; Heinemann, D.; Kalies, S.; Willenbrock, S.; Murua Escobar, H.; Buch, A.; Sodeik, B.; Ripken, T.; Meyer, H.

    2014-03-01

    Alternative high throughput transfection methods are required to understand the molecular network of the cell, which is linked to the evaluation of target genes as therapeutic agents. Besides diagnostic purposes, the transfection of primary- and stem cells is of high interest for therapeutic use. Here, the cell release of trans- or exogene proteins is used to develop immune cancer therapies. The basic requirement to accomplish manipulation of cells is an efficient and gentle transfection method. Therefore, we developed an automatized cell manipulation platform providing high throughput by using GNOME laser transfection. Herein, the interaction of moderately focused laser pulses with gold nanoparticles in close vicinity to the cell membrane mediate transient membrane permeabilization. The exact nature of the involved permeabilization effects depends on the applied particles and laser parameters. Hereinafter, we describe investigations considering the parameter regime, the permeabilization mechanism and the safety profile of GNOME laser transfection. The experimental and calculated results imply a combined permeabilization mechanism consisting of both photochemical and photothermal effects. Furthermore, paramount spatial control achieved either by laser illumination with micrometer precision or targeted gold nanoparticle binding to the cells was demonstrated, allowing selective cell manipulation and destruction. Additionally, the possibility to manipulate difficult to transfect primary cells (neurons) is shown. These results give insights in the basic mechanisms involved in GNOME laser transfection and serve as a strong basis to deliver different molecules for therapeutic (e.g. proteins) and diagnostic (siRNA) use.

  20. Investigation of water structure in nafion membranes by infrared spectroscopy and molecular dynamics simulation.

    PubMed

    Hofmann, Detlef W M; Kuleshova, Liudmila; D'Aguanno, Bruno; Di Noto, Vito; Negro, Enrico; Conti, Fosca; Vittadello, Michele

    2009-01-22

    The structure and interactions of water species in hydrated Nafion membranes as a function of water content were investigated on the basis of medium-infrared spectral analysis and molecular dynamics (MD) simulations. The spectral decomposition of the FT-IR data in the stretching OH region was performed on different levels of hydration of the sulfate functional groups (lambdaH2O/RSO3- = 2-22). Quantum mechanical calculations of two model systems [perfluoroethanesulfonic acid/(H2O)6 cluster] and a [perfluorobutanesulfonic acid/(H2O)6 crystal] were carried out in order to account for the band assignments of Nafion in the stretching OH region (2500-4000 cm-1). Our findings indicated that the secondary structure of water species in Nafion can be accurately explained in terms of our reactive force field for water. The distinction between "surface" and "bulk" water contributions in Nafion membrane pores is proposed along with a quantitative estimate of the different types of OH groups present in the system. The average pore size was calculated and supported by the spectral results. PMID:19113878

  1. A molecular dynamics investigation on the crizotinib resistance mechanism of C1156Y mutation in ALK

    SciTech Connect

    Sun, Hui-Yong; Ji, Feng-Qin

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer The study revealed the detailed resistance mechanism of the non-active mutation C1156Y in ALK. Black-Right-Pointing-Pointer C1156Y leads to crizotinib displacement and conformational changes in the binding cavity. Black-Right-Pointing-Pointer The conformations cause a decline in the vdW and electrostatic energy between crizotinib and ALK. -- Abstract: Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor that has recently been approved in the US for the treatment of non-small cell lung carcinoma (NSCLC). Despite its outstanding safety and efficacy, several resistant mutations against crizotinib have been detected in the treatment of NSCLC. However, in contrast to the widely accepted mechanism of steric hindrance by mutations at the active site, the mechanism by which the C1156Y non-active site mutation confers resistance against crizotinib remains unclear. In the present study, the resistance mechanism of C1156Y in ALK was investigated using molecular dynamics simulations. The results suggest that despite the non-active site mutation, C1156Y causes the dislocation of crizotinib as well as the indirect conformational changes in the binding cavity, which results in a marked decrease in the van der Waals and electrostatic interactions between crizotinib and ALK. The obtained results provide a detailed explanation of the resistance caused by C1156Y and may give a vital clue for the design of drugs to combat crizotinib resistance.

  2. Theoretical investigation of the molecular structures and excitation spectra of triphenylamine and its derivatives

    NASA Astrophysics Data System (ADS)

    Sumimoto, Michinori; Yokogawa, Daisuke; Komeda, Masahiro; Yamamoto, Hidetoshi; Hori, Kenji; Fujimoto, Hitoshi

    2011-10-01

    The molecular geometries, electronic structures, and excitation energies of NPh 3, NPh 2Me, NPhMe 2, and NMe 3, were investigated using DFT and post-Hartree Fock methods. When the structural stabilities of these compounds were compared to results obtained by using MP4(SDQ) method, it was confirmed that the optimized geometries by using MP2 method were sufficiently reliable. The excited states with large oscillator strengths consisted of transition components from the HOMO. It should be noted that the orbitals of the nitrogen atom mix with the π-orbital of the phenyl group in an anti-bonding way in the HOMO, and the orbital energy increases with this mixing. The unoccupied orbitals are generated from bonding and anti-bonding type interactions between the π-orbitals of the phenyl groups; therefore, the number of phenyl groups strongly affects the energy diagram of the compounds studied. The differences in the energy diagram cause a spectral change in these compounds in the ultraviolet region.

  3. Low-dose laulimalide represents a novel molecular probe for investigating microtubule organization

    PubMed Central

    Bennett, Melissa J.; Chan, Gordon K.; Rattner, J.B.; Schriemer, David C.

    2012-01-01

    Laulimalide is a natural product that has strong taxoid-like properties but binds to a distinct site on β-tubulin in the microtubule (MT) lattice. At elevated concentrations, it generates MTs that are resistant to depolymerization, and it induces a conformational state indistinguishable from taxoid-treated MTs. In this study, we describe the effect of low-dose laulimalide on various stages of the cell cycle and compare these effects to docetaxel as a representative of taxoid stabilizers. No evidence of MT bundling in interphase was observed with laulimalide, in spite of the fact that MTs are stabilized at low dose. Cells treated with laulimalide enter mitosis but arrest at prometaphase by generating multiple asters that coalesce into supernumerary poles and interfere with the integrity of the metaphase plate. Cells with a preformed bipolar spindle exist under heightened tension under laulimalide treatment, and chromosomes rapidly shear from the plate, even though the bipolar spindle is well-preserved. Docetaxel generates a similar phenotype for HeLa cells entering mitosis, but when treated at metaphase, cells undergo chromosomal fragmentation and demonstrate reduced centromere dynamics, as expected for a taxoid. Our results suggest that laulimalide represents a new class of molecular probe for investigating MT-mediated events, such as kinetochore-MT interactions, which may reflect the location of the ligand binding site within the interprotofilament groove. PMID:22871740

  4. Low-dose laulimalide represents a novel molecular probe for investigating microtubule organization.

    PubMed

    Bennett, Melissa J; Chan, Gordon K; Rattner, J B; Schriemer, David C

    2012-08-15

    Laulimalide is a natural product that has strong taxoid-like properties but binds to a distinct site on β-tubulin in the microtubule (MT) lattice. At elevated concentrations, it generates MTs that are resistant to depolymerization, and it induces a conformational state indistinguishable from taxoid-treated MTs. In this study, we describe the effect of low-dose laulimalide on various stages of the cell cycle and compare these effects to docetaxel as a representative of taxoid stabilizers. No evidence of MT bundling in interphase was observed with laulimalide, in spite of the fact that MTs are stabilized at low dose. Cells treated with laulimalide enter mitosis but arrest at prometaphase by generating multiple asters that coalesce into supernumerary poles and interfere with the integrity of the metaphase plate. Cells with a preformed bipolar spindle exist under heightened tension under laulimalide treatment, and chromosomes rapidly shear from the plate, even though the bipolar spindle is well-preserved. Docetaxel generates a similar phenotype for HeLa cells entering mitosis, but when treated at metaphase, cells undergo chromosomal fragmentation and demonstrate reduced centromere dynamics, as expected for a taxoid. Our results suggest that laulimalide represents a new class of molecular probe for investigating MT-mediated events, such as kinetochore-MT interactions, which may reflect the location of the ligand binding site within the interprotofilament groove. PMID:22871740

  5. Elizabethkingia anophelis: Molecular Manipulation and Interactions with Mosquito Hosts

    PubMed Central

    Bagdasarian, Michael; Walker, Edward D.

    2015-01-01

    Flavobacteria (members of the family Flavobacteriaceae) dominate the bacterial community in the Anopheles mosquito midgut. One such commensal, Elizabethkingia anophelis, is closely associated with Anopheles mosquitoes through transstadial persistence (i.e., from one life stage to the next); these and other properties favor its development for paratransgenic applications in control of malaria parasite transmission. However, the physiological requirements of E. anophelis have not been investigated, nor has its capacity to perpetuate despite digestion pressure in the gut been quantified. To this end, we first developed techniques for genetic manipulation of E. anophelis, including selectable markers, reporter systems (green fluorescent protein [GFP] and NanoLuc), and transposons that function in E. anophelis. A flavobacterial expression system based on the promoter PompA was integrated into the E. anophelis chromosome and showed strong promoter activity to drive GFP and NanoLuc reporter production. Introduced, GFP-tagged E. anophelis associated with mosquitoes at successive developmental stages and propagated in Anopheles gambiae and Anopheles stephensi but not in Aedes triseriatus mosquitoes. Feeding NanoLuc-tagged cells to A. gambiae and A. stephensi in the larval stage led to infection rates of 71% and 82%, respectively. In contrast, a very low infection rate (3%) was detected in Aedes triseriatus mosquitoes under the same conditions. Of the initial E. anophelis cells provided to larvae, 23%, 71%, and 85% were digested in A. stephensi, A. gambiae, and Aedes triseriatus, respectively, demonstrating that E. anophelis adapted to various mosquito midgut environments differently. Bacterial cell growth increased up to 3-fold when arginine was supplemented in the defined medium. Furthermore, the number of NanoLuc-tagged cells in A. stephensi significantly increased when arginine was added to a sugar diet, showing it to be an important amino acid for E. anophelis. Animal

  6. Investigating the interactions of yeast prions: [SWI+], [PSI+], and [PIN+].

    PubMed

    Du, Zhiqiang; Li, Liming

    2014-06-01

    Multiple prion elements, which are transmitted as heritable protein conformations and often linked to distinct phenotypes, have been identified in the budding yeast, Saccharomyces cerevisiae. It has been shown that overproduction of a prion protein Swi1 can promote the de novo conversion of another yeast prion [PSI(+)] when Sup35 is co-overproduced. However, the mechanism underlying this Pin(+) ([PSI(+)] inducible) activity is not clear. Moreover, how the Swi1 prion ([SWI(+)]) interacts with other yeast prions is unknown. Here, we demonstrate that the Pin(+) activity associated with Swi1 overproduction is independent of Rnq1 expression or [PIN(+)] conversion. We also show that [SWI(+)] enhances the appearance of [PSI(+)] and [PIN(+)]. However, [SWI(+)] significantly compromises the Pin(+) activity of [PIN(+)] when they coexist. We further demonstrate that a single yeast cell can harbor three prions, [PSI(+)], [PIN(+)], and [SWI(+)], simultaneously. However, under this condition, [SWI(+)] is significantly destabilized. While the propensity to aggregate underlies prionogenesis, Swi1 and Rnq1 aggregates resulting from overproduction are usually nonheritable. Conversely, prion protein aggregates formed in nonoverexpressing conditions or induced by preexisting prion(s) are more prionogenic. For [PSI(+)] and [PIN(+)] de novo formation, heterologous "facilitators," such as preexisting [SWI(+)] aggregates, colocalize only with the newly formed ring-/rod-shaped Sup35 or Rnq1 aggregates, but not with the dot-shaped mature prion aggregates. Their colocalization frequency is coordinated with their prion inducibility, indicating that prion-prion interactions mainly occur at the early initiation stage. Our results provide supportive evidence for the cross-seeding model of prionogenesis and highlight a complex interaction network among prions in yeast.

  7. From molecular interaction to acute promyelocytic leukemia: Calculating leukemogenesis and remission from endogenous molecular-cellular network

    PubMed Central

    Yuan, Ruoshi; Zhu, Xiaomei; Radich, Jerald P.; Ao, Ping

    2016-01-01

    Acute promyelocytic leukemia (APL) remains the best example of a malignancy that can be cured clinically by differentiation therapy. We demonstrate that APL may emerge from a dynamical endogenous molecular-cellular network obtained from normal, non-cancerous molecular interactions such as signal transduction and translational regulation under physiological conditions. This unifying framework, which reproduces APL, normal progenitor, and differentiated granulocytic phenotypes as different robust states from the network dynamics, has the advantage to study transition between these states, i.e. critical drivers for leukemogenesis and targets for differentiation. The simulation results quantitatively reproduce microarray profiles of NB4 and HL60 cell lines in response to treatment and normal neutrophil differentiation, and lead to new findings such as biomarkers for APL and additional molecular targets for arsenic trioxide therapy. The modeling shows APL and normal states mutually suppress each other, both in “wiring” and in dynamical cooperation. Leukemogenesis and recovery under treatment may be a consequence of spontaneous or induced transitions between robust states, through “passes” or “dragging” by drug effects. Our approach rationalizes leukemic complexity and constructs a platform towards extending differentiation therapy by performing “dry” molecular biology experiments. PMID:27098097

  8. Modeling techniques and fluorescence imaging investigation of the interactions of an anthraquinone derivative with HSA and ctDNA.

    PubMed

    Fu, Zheng; Cui, Yanrui; Cui, Fengling; Zhang, Guisheng

    2016-01-15

    A new anthraquinone derivative (AORha) was synthesized. Its interactions with human serum albumin (HSA) and calf thymus DNA (ctDNA) were investigated by fluorescence spectroscopy, UV-visible absorption spectroscopy and molecular modeling. Cell viability assay and cell imaging experiment were performed using cervical cancer cells (HepG2 cells). The fluorescence results revealed that the quenching mechanism was static quenching. At different temperatures (290, 300, 310 K), the binding constants (K) and the number of binding sites (n) were determined, respectively. The positive ΔH and ΔS values showed that the binding of AORha with HSA was hydrophobic force, which was identical with the molecular docking result. Studying the fluorescence spectra, UV spectra and molecular modeling also verified that the binding mode of AORha and ctDNA might be intercalative. When HepG2 cells were treated with AORha, the fluorescence became brighter and turned green, which could be used for bioimaging.

  9. Modeling techniques and fluorescence imaging investigation of the interactions of an anthraquinone derivative with HSA and ctDNA

    NASA Astrophysics Data System (ADS)

    Fu, Zheng; Cui, Yanrui; Cui, Fengling; Zhang, Guisheng

    2016-01-01

    A new anthraquinone derivative (AORha) was synthesized. Its interactions with human serum albumin (HSA) and calf thymus DNA (ctDNA) were investigated by fluorescence spectroscopy, UV-visible absorption spectroscopy and molecular modeling. Cell viability assay and cell imaging experiment were performed using cervical cancer cells (HepG2 cells). The fluorescence results revealed that the quenching mechanism was static quenching. At different temperatures (290, 300, 310 K), the binding constants (K) and the number of binding sites (n) were determined, respectively. The positive ΔH and ΔS values showed that the binding of AORha with HSA was hydrophobic force, which was identical with the molecular docking result. Studying the fluorescence spectra, UV spectra and molecular modeling also verified that the binding mode of AORha and ctDNA might be intercalative. When HepG2 cells were treated with AORha, the fluorescence became brighter and turned green, which could be used for bioimaging.

  10. Characterization of intermolecular interaction between cyanidin-3-glucoside and bovine serum albumin: spectroscopic and molecular docking methods.

    PubMed

    Shi, Jie-hua; Wang, Jing; Zhu, Ying-yao; Chen, Jun

    2014-08-01

    The intermolecular interaction between cyanidin-3-glucoside (Cy-3-G) and bovine serum albumin (BSA) was investigated using fluorescence, circular dichroism and molecular docking methods. The experimental results revealed that the fluorescence quenching of BSA at 338 nm by Cy-3-G resulted from the formation of Cy-3-G-BSA complex. The number of binding sites (n) for Cy-3-G binding on BSA was approximately equal to 1. The experimental and molecular docking results revealed that after binding Cy-3-G to BSA, Cy-3-G is closer to the Tyr residue than the Trp residue, the secondary structure of BSA almost not change, the binding process of Cy-3-G with BSA is spontaneous, and Cy-3-G can be inserted into the hydrophobic cavity of BSA (site II') in the binding process of Cy-3-G with BSA. Moreover, based on the sign and magnitude of the enthalpy and entropy changes (ΔH(0)  = - 29.64 kcal/mol and ΔS(0)  = - 69.51 cal/mol K) and the molecular docking results, it can be suggested that the main interaction forces of Cy-3-G with BSA are Van der Waals and hydrogen bonding interactions.

  11. Specific interactions between lactose repressor protein and DNA affected by ligand binding: ab initio molecular orbital calculations.

    PubMed

    Ohyama, Tatsuya; Hayakawa, Masato; Nishikawa, Shin; Kurita, Noriyuki

    2011-06-01

    Transcription mechanisms of gene information from DNA to mRNA are essentially controlled by regulatory proteins such as a lactose repressor (LacR) protein and ligand molecules. Biochemical experiments elucidated that a ligand binding to LacR drastically changes the mechanism controlled by LacR, although the effect of ligand binding has not been clarified at atomic and electronic levels. We here investigated the effect of ligand binding on the specific interactions between LacR and operator DNA by the molecular simulations combined with classical molecular mechanics and ab initio fragment molecular orbital methods. The results indicate that the binding of anti-inducer ligand strengthens the interaction between LacR and DNA, which is consistent with the fact that the binding of anti-inducer enhances the repression of gene transcription by LacR. It was also elucidated that hydrating water molecules existing between LacR and DNA contribute to the specific interactions between LacR and DNA. PMID:21328406

  12. Molecular docking and dynamics simulations on the interaction of cationic porphyrin-anthraquinone hybrids with DNA G-quadruplexes.

    PubMed

    Arba, Muhammad; Kartasasmita, Rahmana E; Tjahjono, Daryono H

    2016-01-01

    A series of cationic porphyrin-anthraquinone hybrids bearing either pyridine, imidazole, or pyrazole rings at the meso-positions have been investigated for their interaction with DNA G-quadruplexes by employing molecular docking and molecular dynamics simulations. Three types of DNA G-quadruplexes were utilized, which comprise parallel, antiparallel, and mixed hybrid topologies. The porphyrin hybrids have a preference to bind with parallel and mixed hybrid structures compared to the antiparallel structure. This preference arises from the end stacking of porphyrin moiety following G-stem and loop binding of anthraquinone tail, which is not found in the antiparallel due to the presence of diagonal and lateral loops that crowd the G-quartet. The binding to the antiparallel, instead, occurred with poorer affinity through both the loop and wide groove. All sites of porphyrin binding were confirmed by 6 ns molecular dynamics simulation, as well as by the negative value of the total binding free energies that were calculated using the MMPBSA method. Free energy analysis shows that the favorable contribution came from the electrostatic term, which supposedly originated from the interaction of either cationic pyridinium, pyrazole, or imidazole groups and the anionic phosphate backbone, and also from the van der Waals energy, which primarily contributed through end stacking interaction.

  13. Adaptive GPU-accelerated force calculation for interactive rigid molecular docking using haptics.

    PubMed

    Iakovou, Georgios; Hayward, Steven; Laycock, Stephen D

    2015-09-01

    Molecular docking systems model and simulate in silico the interactions of intermolecular binding. Haptics-assisted docking enables the user to interact with the simulation via their sense of touch but a stringent time constraint on the computation of forces is imposed due to the sensitivity of the human haptic system. To simulate high fidelity smooth and stable feedback the haptic feedback loop should run at rates of 500Hz to 1kHz. We present an adaptive force calculation approach that can be executed in parallel on a wide range of Graphics Processing Units (GPUs) for interactive haptics-assisted docking with wider applicability to molecular simulations. Prior to the interactive session either a regular grid or an octree is selected according to the available GPU memory to determine the set of interatomic interactions within a cutoff distance. The total force is then calculated from this set. The approach can achieve force updates in less than 2ms for molecular structures comprising hundreds of thousands of atoms each, with performance improvements of up to 90 times the speed of current CPU-based force calculation approaches used in interactive docking. Furthermore, it overcomes several computational limitations of previous approaches such as pre-computed force grids, and could potentially be used to model receptor flexibility at haptic refresh rates.

  14. Adaptive GPU-accelerated force calculation for interactive rigid molecular docking using haptics.

    PubMed

    Iakovou, Georgios; Hayward, Steven; Laycock, Stephen D

    2015-09-01

    Molecular docking systems model and simulate in silico the interactions of intermolecular binding. Haptics-assisted docking enables the user to interact with the simulation via their sense of touch but a stringent time constraint on the computation of forces is imposed due to the sensitivity of the human haptic system. To simulate high fidelity smooth and stable feedback the haptic feedback loop should run at rates of 500Hz to 1kHz. We present an adaptive force calculation approach that can be executed in parallel on a wide range of Graphics Processing Units (GPUs) for interactive haptics-assisted docking with wider applicability to molecular simulations. Prior to the interactive session either a regular grid or an octree is selected according to the available GPU memory to determine the set of interatomic interactions within a cutoff distance. The total force is then calculated from this set. The approach can achieve force updates in less than 2ms for molecular structures comprising hundreds of thousands of atoms each, with performance improvements of up to 90 times the speed of current CPU-based force calculation approaches used in interactive docking. Furthermore, it overcomes several computational limitations of previous approaches such as pre-computed force grids, and could potentially be used to model receptor flexibility at haptic refresh rates. PMID:26186491

  15. Predicting Protein-Protein Interactions from the Molecular to the Proteome Level.

    PubMed

    Keskin, Ozlem; Tuncbag, Nurcan; Gursoy, Attila

    2016-04-27

    Identification of protein-protein interactions (PPIs) is at the center of molecular biology considering the unquestionable role of proteins in cells. Combinatorial interactions result in a repertoire of multiple functions; hence, knowledge of PPI and binding regions naturally serve to functional proteomics and drug discovery. Given experimental limitations to find all interactions in a proteome, computational prediction/modeling of protein interactions is a prerequisite to proceed on the way to complete interactions at the proteome level. This review aims to provide a background on PPIs and their types. Computational methods for PPI predictions can use a variety of biological data including sequence-, evolution-, expression-, and structure-based data. Physical and statistical modeling are commonly used to integrate these data and infer PPI predictions. We review and list the state-of-the-art methods, servers, databases, and tools for protein-protein interaction prediction. PMID:27074302

  16. Molecular Principles of Gene Fusion Mediated Rewiring of Protein Interaction Networks in Cancer.

    PubMed

    Latysheva, Natasha S; Oates, Matt E; Maddox, Louis; Flock, Tilman; Gough, Julian; Buljan, Marija; Weatheritt, Robert J; Babu, M Madan

    2016-08-18

    Gene fusions are common cancer-causing mutations, but the molecular principles by which fusion protein products affect interaction networks and cause disease are not well understood. Here, we perform an integrative analysis of the structural, interactomic, and regulatory properties of thousands of putative fusion proteins. We demonstrate that genes that form fusions (i.e., parent genes) tend to be highly connected hub genes, whose protein products are enriched in structured and disordered interaction-mediating features. Fusion often results in the loss of these parental features and the depletion of regulatory sites such as post-translational modifications. Fusion products disproportionately connect proteins that did not previously interact in the protein interaction network. In this manner, fusion products can escape cellular regulation and constitutively rewire protein interaction networks. We suggest that the deregulation of central, interaction-prone proteins may represent a widespread mechanism by which fusion proteins alter the topology of cellular signaling pathways and promote cancer. PMID:27540857

  17. Molecular Principles of Gene Fusion Mediated Rewiring of Protein Interaction Networks in Cancer.

    PubMed

    Latysheva, Natasha S; Oates, Matt E; Maddox, Louis; Flock, Tilman; Gough, Julian; Buljan, Marija; Weatheritt, Robert J; Babu, M Madan

    2016-08-18

    Gene fusions are common cancer-causing mutations, but the molecular principles by which fusion protein products affect interaction networks and cause disease are not well understood. Here, we perform an integrative analysis of the structural, interactomic, and regulatory properties of thousands of putative fusion proteins. We demonstrate that genes that form fusions (i.e., parent genes) tend to be highly connected hub genes, whose protein products are enriched in structured and disordered interaction-mediating features. Fusion often results in the loss of these parental features and the depletion of regulatory sites such as post-translational modifications. Fusion products disproportionately connect proteins that did not previously interact in the protein interaction network. In this manner, fusion products can escape cellular regulation and constitutively rewire protein interaction networks. We suggest that the deregulation of central, interaction-prone proteins may represent a widespread mechanism by which fusion proteins alter the topology of cellular signaling pathways and promote cancer.

  18. An Analytical Investigation of Wing-Jet Interaction

    NASA Technical Reports Server (NTRS)

    Lan, E. C.

    1974-01-01

    The aerodynamic interaction between the wing and an inviscid jet with Mach number nonuniformity is formulated by using a two-vortex-sheet model for the jet. One of the vortex sheets accounts for the induced jet flow and the other the induced outer flow. No additional source distribution is needed for the jet at an angle of attack. The above problem is solved by satisfying the jet and wing tangency and the jet pressure-continuity conditions and using a quasi vortex lattice method for computing the induced flow field. The latter method is derived through theoretical consideration by properly accounting for singularities present in the equations and possesses the same simplicity and generality as the conventional vortex lattice method but has a better rate of numerical convergence. The resulting system of algebraic equations is solved by Purcell's vector method. The numerical formulation is first applied to the wing-slipstream interaction problem. Results for one centered-jet configuration are compared with those predicted by some existing theories.

  19. Investigating the interaction between acoustically stimulated microbubbles and fibrin clots

    NASA Astrophysics Data System (ADS)

    Acconcia, Christopher; Leung, Ben; Hynynen, Kullervo; Goertz, David

    2012-11-01

    While it is well established that ultrasound stimulated microbubbles can potentiate thrombolysis, the mechanisms of action are poorly understood. The objective of this work was to gain a more fundamental understanding of how acoustically stimulated microbubbles interact with and potentially degrade fibrin clots. Owing to their optical transparency, the use of fibrin clots allowed to optically observe microbubbles interacting with the clot boundary and any resultant disruption of the fluorescently tagged fibrin network. It was found that microbubbles could readily penetrate into fibrin clots with velocities up to 0.2 m/s and to depths related to the number of pulses applied. At lower pressures (0.2-0.55 MPa), microbubbles as small as 3μm were observed to penetrate, whereas higher pressures (>0.9 MPa) caused the penetration of larger microbubbles (10-30μm), formed by coalescence prior to entry. In some cases, patent 'tunnels' remained along the path taken by penetrating microbubbles. Tunnel diameters ranged between 9-35μm depending largely on pressure and pulse duration. Two-photon microscopy indicated either patent tunnels or paths of disrupted fibers consistent with collapsed tunnel. Fluid flow within the clot was observed to accompany penetrating microbubbles, which may have implications for lytic enzyme penetration.

  20. Investigation of radiative interactions in supersonic internal flows

    NASA Technical Reports Server (NTRS)

    Tiwari, Surendra N.; Thomas, A. M.

    1991-01-01

    Analyses and numerical procedures are presented to study the radiative interactions of absorbing emitting species in chemically reacting supersonic flow in various ducts. The 2-D time dependent Navier-Stokes equations in conjunction with radiative flux equation are used to study supersonic flows undergoing finite rate chemical reaction in a hydrogen air system. The specific problem considered is the flow of premixed radiating gas between parallel plates. Specific attention was directed toward studying the radiative contribution of H2O, OH, and NO under realistic physical and flow conditions. Results are presented for the radiative flux obtained for different gases and for various combination of these gases. The problem of chemically reacting and radiating flows was solved for the flow of premixed hydrogen-air through a 10 deg compression ramp. Results demonstrate that the radiative interaction increases with an increase in pressure, temperature, amount of participating species, plate spacing, and Mach number. Most of the energy, however, is transferred by convection in the flow direction. In general the results indicate that radiation can have a significant effect on the entire flow field.

  1. How does the molecular linker in dynamic force spectroscopy affect probing molecular interactions at the single-molecule level?

    NASA Astrophysics Data System (ADS)

    Taninaka, Atsushi; Aizawa, Kota; Hanyu, Tatsuya; Hirano, Yuuichi; Takeuchi, Osamu; Shigekawa, Hidemi

    2016-08-01

    Dynamic force spectroscopy (DFS) based on atomic force microscopy, which enables us to obtain information on the interaction potential between molecules such as antigen-antibody complexes at the single-molecule level, is a key technique for advancing molecular science and technology. However, to ensure the reliability of DFS measurement, its basic mechanism must be well understood. We examined the effect of the molecular linker used to fix the target molecule to the atomic force microscope cantilever, i.e., the force direction during measurement, for the first time, which has not been discussed until now despite its importance. The effect on the lifetime and barrier position, which can be obtained by DFS, was found to be ˜10 and ˜50%, respectively, confirming the high potential of DFS.

  2. How does the molecular linker in dynamic force spectroscopy affect probing molecular interactions at the single-molecule level?

    NASA Astrophysics Data System (ADS)

    Taninaka, Atsushi; Aizawa, Kota; Hanyu, Tatsuya; Hirano, Yuuichi; Takeuchi, Osamu; Shigekawa, Hidemi

    2016-08-01

    Dynamic force spectroscopy (DFS) based on atomic force microscopy, which enables us to obtain information on the interaction potential between molecules such as antigen–antibody complexes at the single-molecule level, is a key technique for advancing molecular science and technology. However, to ensure the reliability of DFS measurement, its basic mechanism must be well understood. We examined the effect of the molecular linker used to fix the target molecule to the atomic force microscope cantilever, i.e., the force direction during measurement, for the first time, which has not been discussed until now despite its importance. The effect on the lifetime and barrier position, which can be obtained by DFS, was found to be ∼10 and ∼50%, respectively, confirming the high potential of DFS.

  3. Comparing position and force control for interactive molecular simulators with haptic feedback.

    PubMed

    Bolopion, Aude; Cagneau, Barthélemy; Redon, Stephane; Régnier, Stéphane

    2010-09-01

    This paper presents a novel tool for the analysis of new molecular structures which enables a wide variety of manipulations. It is composed of a molecular simulator and a haptic device. The simulation software deals with systems of hundreds or thousands of degrees of freedom and computes the reconfiguration of the molecules in a few tenths of a second. For the ease of manipulation and to help the operator understand nanoscale phenomena, a haptic device is connected to the simulator. To handle a wide variety of applications, both position and force control are implemented. To our knowledge, this is the first time the applications of force control are detailed for molecular simulation. These two control modes are compared in terms of adequacy with molecular dynamics, transparency and stability sensitivity with respect to environmental conditions. Based on their specificity the operations they can realize are detailed. Experiments highlight the usability of our tool for the different steps of the analysis of molecular structures. It includes the global reconfiguration of a molecular system, the measurement of molecular properties and the comprehension of nanoscale interactions. Compared to most existing systems, the one developed in this paper offers a wide range of possible experiments. The detailed analysis of the properties of the control modes can be easily used to implement haptic feedback on other molecular simulators. PMID:20727801

  4. Deciphering the GPER/GPR30-agonist and antagonists interactions using molecular modeling studies, molecular dynamics, and docking simulations.

    PubMed

    Méndez-Luna, D; Martínez-Archundia, M; Maroun, Rachid C; Ceballos-Reyes, G; Fragoso-Vázquez, M J; González-Juárez, D E; Correa-Basurto, J

    2015-01-01

    The G-protein coupled estrogen receptor 1 GPER/GPR30 is a transmembrane seven-helix (7TM) receptor involved in the growth and proliferation of breast cancer. Due to the absence of a crystal structure of GPER/GPR30, in this work, molecular modeling studies have been carried out to build a three-dimensional structure, which was subsequently refined by molecular dynamics (MD) simulations (up to 120 ns). Furthermore, we explored GPER/GPR30's molecular recognition properties by using reported agonist ligands (G1, estradiol (E2), tamoxifen, and fulvestrant) and the antagonist ligands (G15 and G36) in subsequent docking studies. Our results identified the E2 binding site on GPER/GPR30, as well as other receptor cavities for accepting large volume ligands, through GPER/GPR30 π-π, hydrophobic, and hydrogen bond interactions. Snapshots of the MD trajectory at 14 and 70 ns showed almost identical binding motifs for G1 and G15. It was also observed that C107 interacts with the acetyl oxygen of G1 (at 14 ns) and that at 70 ns the residue E275 interacts with the acetyl group and with the oxygen from the other agonist whereas the isopropyl group of G36 is oriented toward Met141, suggesting that both C107 and E275 could be involved in the protein activation. This contribution suggest that GPER1 has great structural changes which explain its great capacity to accept diverse ligands, and also, the same ligand could be recognized in different binding pose according to GPER structural conformations.

  5. Experimental investigation of unsteady fan flow interaction with downstream struts

    NASA Technical Reports Server (NTRS)

    Ng, W. F.; Obrien, W. F.; Olsen, T. L.

    1986-01-01

    In the present study of the unsteady pressure field produced on fan rotor blades by interaction with downstream struts, a single stage, low speed axial-flow fan was instrumented with blade-mounted high frequency pressure transducers. In addition, stationary pressure problems were used to map out the flowfield. Fluctuating pressure measurements are presented for blade midspan and 85-percent span on both the suction and pressure surfaces of the rotor blades at several positions of the downstream struts, and for two different flow coefficients. The strut is found to produce an effect on the unsteady pressure field on the rotor blades; this effect exceeds that due to the stator at design rotor-stator-strut spacing, but it rapidly declines as the struts are moved downstream.

  6. Molecular Dynamics Study on the Biophysical Interactions of Seven Green Tea Catechins with Cell Membranes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Molecular dynamics simulations were performed to study the interactions of bioactive catechins (flavonoids) commonly found in green tea with lipid bilayers, as model for cell membranes. Previously, a number of experimental studies rationalized catechin’s anticarcinogenic, antibacterial, and other be...

  7. Structural aspects of the solvation shell of lysine and acetylated lysine: A Car-Parrinello and classical molecular dynamics investigation

    SciTech Connect

    Carnevale, V.; Raugei, S.

    2009-12-14

    Lysine acetylation is a post-translational modification, which modulates the affinity of protein-protein and/or protein-DNA complexes. Its crucial role as a switch in signaling pathways highlights the relevance of charged chemical groups in determining the interactions between water and biomolecules. A great effort has been recently devoted to assess the reliability of classical molecular dynamics simulations in describing the solvation properties of charged moieties. In the spirit of these investigations, we performed classical and Car-Parrinello molecular dynamics simulations on lysine and acetylated-lysine in aqueous solution. A comparative analysis between the two computational schemes is presented with a focus on the first solvation shell of the charged groups. An accurate structural analysis unveils subtle, yet statistically significant, differences which are discussed in connection to the significant electronic density charge transfer occurring between the solute and the surrounding water molecules.

  8. Adsorption mechanisms of microcystin variant conformations at water-mineral interfaces: A molecular modeling investigation.

    PubMed

    Pochodylo, Amy L; Aoki, Thalia G; Aristilde, Ludmilla

    2016-10-15

    Microcystins (MCs) are potent toxins released during cyanobacterial blooms. Clay minerals are implicated in trapping MCs within soil particles in surface waters and sediments. In the absence of molecular characterization, the relevance of previously proposed adsorption mechanisms is lacking. Towards obtaining this characterization, we conducted Monte Carlo simulations combined with molecular dynamics relaxation of two MC variants, MC-leucine-arginine (MC-LR) and MC-leucine-alanine (MC-LA), adsorbed on hydrated montmorillonite with different electrolytes. The resulting adsorbate structures revealed how MC conformations and aqueous conditions dictate binding interactions at the mineral surface. Electrostatic coupling between the arginine residue and a carboxylate in MC-LR excluded the participation of arginine in mediating adsorption on montmorillonite in a NaCl solution. However, in a CaCl2 solution, the complexation of Ca by two carboxylate moieties in MC-LR changed the MC conformation, which allowed arginine to mediate electrostatic interaction with the mineral. By contrast, due to the lack of arginine in MC-LA, complexation of Ca by only one carboxylate in MC-LA was required to favor Ca-bridging interaction with the mineral. Multiple water-bridged H-bonding interactions were also important in anchoring MCs at the mineral surface. Our modeling results offer molecular insights into the structural and chemical factors that can control the fate of MCs at water-mineral interfaces.

  9. Adsorption mechanisms of microcystin variant conformations at water-mineral interfaces: A molecular modeling investigation.

    PubMed

    Pochodylo, Amy L; Aoki, Thalia G; Aristilde, Ludmilla

    2016-10-15

    Microcystins (MCs) are potent toxins released during cyanobacterial blooms. Clay minerals are implicated in trapping MCs within soil particles in surface waters and sediments. In the absence of molecular characterization, the relevance of previously proposed adsorption mechanisms is lacking. Towards obtaining this characterization, we conducted Monte Carlo simulations combined with molecular dynamics relaxation of two MC variants, MC-leucine-arginine (MC-LR) and MC-leucine-alanine (MC-LA), adsorbed on hydrated montmorillonite with different electrolytes. The resulting adsorbate structures revealed how MC conformations and aqueous conditions dictate binding interactions at the mineral surface. Electrostatic coupling between the arginine residue and a carboxylate in MC-LR excluded the participation of arginine in mediating adsorption on montmorillonite in a NaCl solution. However, in a CaCl2 solution, the complexation of Ca by two carboxylate moieties in MC-LR changed the MC conformation, which allowed arginine to mediate electrostatic interaction with the mineral. By contrast, due to the lack of arginine in MC-LA, complexation of Ca by only one carboxylate in MC-LA was required to favor Ca-bridging interaction with the mineral. Multiple water-bridged H-bonding interactions were also important in anchoring MCs at the mineral surface. Our modeling results offer molecular insights into the structural and chemical factors that can control the fate of MCs at water-mineral interfaces. PMID:27433998

  10. Enacting the molecular imperative: How gene-environment interaction research links bodies and environments in the post-genomic age.

    PubMed

    Darling, Katherine Weatherford; Ackerman, Sara L; Hiatt, Robert H; Lee, Sandra Soo-Jin; Shim, Janet K

    2016-04-01

    Despite a proclaimed shift from 'nature versus nurture' to 'genes and environment' paradigms within biomedical and genomic science, capturing the environment and identifying gene-environment interactions (GEIs) has remained a challenge. What does 'the environment' mean in the post-genomic age? In this paper, we present qualitative data from a study of 33 principal investigators funded by the U.S. National Institutes of Health to conduct etiological research on three complex diseases (cancer, cardiovascular disease and diabetes). We examine their research practices and perspectives on the environment through the concept of molecularization: the social processes and transformations through which phenomena (diseases, identities, pollution, food, racial/ethnic classifications) are re-defined in terms of their molecular components and described in the language of molecular biology. We show how GEI researchers' expansive conceptualizations of the environment ultimately yield to the imperative to molecularize and personalize the environment. They seek to 'go into the body' and re-work the boundaries between bodies and environments. In the process, they create epistemic hinges to facilitate a turn from efforts to understand social and environmental exposures outside the body, to quantifying their effects inside the body. GEI researchers respond to these emergent imperatives with a mixture of excitement, ambivalence and frustration. We reflect on how GEI researchers struggle to make meaning of molecules in their work, and how they grapple with molecularization as a methodological and rhetorical imperative as well as a process transforming biomedical research practices. PMID:26994357

  11. Enacting the molecular imperative: How gene-environment interaction research links bodies and environments in the post-genomic age.

    PubMed

    Darling, Katherine Weatherford; Ackerman, Sara L; Hiatt, Robert H; Lee, Sandra Soo-Jin; Shim, Janet K

    2016-04-01

    Despite a proclaimed shift from 'nature versus nurture' to 'genes and environment' paradigms within biomedical and genomic science, capturing the environment and identifying gene-environment interactions (GEIs) has remained a challenge. What does 'the environment' mean in the post-genomic age? In this paper, we present qualitative data from a study of 33 principal investigators funded by the U.S. National Institutes of Health to conduct etiological research on three complex diseases (cancer, cardiovascular disease and diabetes). We examine their research practices and perspectives on the environment through the concept of molecularization: the social processes and transformations through which phenomena (diseases, identities, pollution, food, racial/ethnic classifications) are re-defined in terms of their molecular components and described in the language of molecular biology. We show how GEI researchers' expansive conceptualizations of the environment ultimately yield to the imperative to molecularize and personalize the environment. They seek to 'go into the body' and re-work the boundaries between bodies and environments. In the process, they create epistemic hinges to facilitate a turn from efforts to understand social and environmental exposures outside the body, to quantifying their effects inside the body. GEI researchers respond to these emergent imperatives with a mixture of excitement, ambivalence and frustration. We reflect on how GEI researchers struggle to make meaning of molecules in their work, and how they grapple with molecularization as a methodological and rhetorical imperative as well as a process transforming biomedical research practices.

  12. Molecular interactions on single-walled carbon nanotubes revealed by high-resolution transmission microscopy

    NASA Astrophysics Data System (ADS)

    Umeyama, Tomokazu; Baek, Jinseok; Sato, Yuta; Suenaga, Kazu; Abou-Chahine, Fawzi; Tkachenko, Nikolai V.; Lemmetyinen, Helge; Imahori, Hiroshi

    2015-07-01

    The close solid-state structure-property relationships of organic π-aromatic molecules have attracted interest due to their implications for the design of organic functional materials. In particular, a dimeric structure, that is, a unit consisting of two molecules, is required for precisely evaluating intermolecular interactions. Here, we show that the sidewall of a single-walled carbon nanotube (SWNT) represents a unique molecular dimer platform that can be directly visualized using high-resolution transmission electron microscopy. Pyrene is chosen as the π-aromatic molecule; its dimer is covalently linked to the SWNT sidewalls by aryl addition. Reflecting the orientation and separation of the two molecules, the pyrene dimer on the SWNT exhibits characteristic optical and photophysical properties. The methodology discussed here--form and probe molecular dimers--is highly promising for the creation of unique models and provides indispensable and fundamental information regarding molecular interactions.

  13. Molecular Interactions in 1-Ethyl-3-methylimidazolium Acetate Ion Pair: A Density Functional Study

    NASA Astrophysics Data System (ADS)

    Dhumal, Nilesh R.; Kim, Hyung J.; Kiefer, Johannes

    2009-08-01

    The density functional method is used to obtain the molecular structure, electron density topography, and vibrational frequencies of the ion pair 1-ethyl-3-methylimidazolium acetate. Different conformers are simulated on the basis of molecular interactions between the 1-ethyl-3-methylimidazolium cation and acetate anion. The lowest energy conformers exhibit strong C-H···O interionic interactions compared with other conformers. Characteristic vibrational frequencies of the ion pair and their shifts with respect to free ions are analyzed via the natural bond orbitals and difference electron density maps coupled with molecular electron density topology. Theoretically scaled vibrational frequencies are also compared with the spontaneous Raman scattering and attenuated total reflection infrared absorption measurements.

  14. Molecular interactions on single-walled carbon nanotubes revealed by high-resolution transmission microscopy

    PubMed Central

    Umeyama, Tomokazu; Baek, Jinseok; Sato, Yuta; Suenaga, Kazu; Abou-Chahine, Fawzi; Tkachenko, Nikolai V.; Lemmetyinen, Helge; Imahori, Hiroshi

    2015-01-01

    The close solid-state structure–property relationships of organic π−aromatic molecules have attracted interest due to their implications for the design of organic functional materials. In particular, a dimeric structure, that is, a unit consisting of two molecules, is required for precisely evaluating intermolecular interactions. Here, we show that the sidewall of a single-walled carbon nanotube (SWNT) represents a unique molecular dimer platform that can be directly visualized using high-resolution transmission electron microscopy. Pyrene is chosen as the π−aromatic molecule; its dimer is covalently linked to the SWNT sidewalls by aryl addition. Reflecting the orientation and separation of the two molecules, the pyrene dimer on the SWNT exhibits characteristic optical and photophysical properties. The methodology discussed here—form and probe molecular dimers—is highly promising for the creation of unique models and provides indispensable and fundamental information regarding molecular interactions. PMID:26173983

  15. Strong Hydrogen Bonded Molecular Interactions between Atmospheric Diamines and Sulfuric Acid.

    PubMed

    Elm, Jonas; Jen, Coty N; Kurtén, Theo; Vehkamäki, Hanna

    2016-05-26

    We investigate the molecular interaction between methyl-substituted N,N,N',N'-ethylenediamines, propane-1,3-diamine, butane-1,4-diamine, and sulfuric acid using computational methods. Molecular structure of the diamines and their dimer clusters with sulfuric acid is studied using three density functional theory methods (PW91, M06-2X, and ωB97X-D) with the 6-31++G(d,p) basis set. A high level explicitly correlated CCSD(T)-F12a/VDZ-F12 method is used to obtain accurate binding energies. The reaction Gibbs free energies are evaluated and compared with values for reactions involving ammonia and atmospherically relevant monoamines (methylamine, dimethylamine, and trimethylamine). We find that the complex formation between sulfuric acid and the studied diamines provides similar or more favorable reaction free energies than dimethylamine. Diamines that contain one or more secondary amino groups are found to stabilize sulfuric acid complexes more efficiently. Elongating the carbon backbone from ethylenediamine to propane-1,3-diamine or butane-1,4-diamine further stabilizes the complex formation with sulfuric acid by up to 4.3 kcal/mol. Dimethyl-substituted butane-1,4-diamine yields a staggering formation free energy of -19.1 kcal/mol for the clustering with sulfuric acid, indicating that such diamines could potentially be a key species in the initial step in the formation of new particles. For studying larger clusters consisting of a diamine molecule with up to four sulfuric acid molecules, we benchmark and utilize a domain local pair natural orbital coupled cluster (DLPNO-CCSD(T)) method. We find that a single diamine is capable of efficiently stabilizing sulfuric acid clusters with up to four acid molecules, whereas monoamines such as dimethylamine are capable of stabilizing at most 2-3 sulfuric acid molecules. PMID:27128188

  16. Molecular interactions between zoledronic acid and bone: An in vitro Raman microspectroscopic study.

    PubMed

    Juillard, Audrey; Falgayrac, Guillaume; Cortet, Bernard; Vieillard, Marie-Hélène; Azaroual, Nathalie; Hornez, Jean-Christophe; Penel, Guillaume

    2010-11-01

    The aim of this study was to investigate molecular interactions between a bisphosphonate (BP), zoledronic acid, and bone tissue by the use of Raman microspectroscopy. In this way, samples of hydroxyapatite (HA), as a bone model, and Wistar rat femurs were soaking in zoledronic acid solutions. Sample surfaces were studied by Environmental Scanning Electron Microscopy and Raman spectroscopy. The amount of zoledronic acid incorporated onto the samples and the inorganic phosphate released in solution were determined by (31)P NMR spectroscopy. Total carbonate content in solution was evaluated by inorganic carbon analyser. After impregnation new Raman bands with frequencies close to characteristic peaks of zoledronic acid (in particular phosphate moieties and imidazole ring of the R2 side-chain) were observed on both types of samples. Physico-chemical parameters of the bone were also significantly modified (P<0.0001). The mineral to organic ratio and the carbonate to phosphate ratio decreased and the crystallinity increased. Released inorganic phosphate and carbonate were detected in the solutions. The Raman shift of the bands corresponding to the phosphate groups and the imidazole ring of the BP highlight their implication in the binding to the mineral. The detection of released inorganic phosphate and carbonate in solution, the modifications of the mineral to phosphate ratio and the carbonate to phosphate ratio reveal that BP decrease the amount of inorganic phosphate and limit the dissolution of bone mineral. The increase of the crystallinity after BP binding shows a re-organisation of the lattice with a higher symmetry. Thus, it seems that zoledronic acid has an important contribution on the increase of crystallinity. The use of Raman spectrometry brings new and complementary information on the impact of zoledronic acid on bone composition at