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Sample records for investigating molecular interactions

  1. 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.

  2. 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

  3. 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.

  4. Spectroscopic and structural investigation of interaction product of 8-mercaptoquinoline with molecular iodine

    NASA Astrophysics Data System (ADS)

    Chernov'yants, Margarita S.; Starikova, Zoya A.; Karginova, Anastasia O.; Kolesnikova, Tatiana S.; Tereznikov, Alexander Yu.

    2013-11-01

    The behavior of 8-mercaptoquinoline, which is a potential antithyroid drug toward molecular iodine was investigated. The ability of 8-mercaptoquinoline to form the outer-sphere charge-transfer complex C9H7NS·I2 with iodine molecular in dilute chloroform solution has been studied by UV/vis spectroscopy (lg β = 3.14). The crystal structure of the new salt 8-(quinoline-8-yldisulfonyl)quinolinium triiodide - product of irreversible oxidation of 8-mercaptoquinoline was determined by X-ray diffraction. Intramolecular hydrogen bond of N-H⋯N type is presented in the organic cation. The triiodide ion is the nearly centrosymmetrical anion. The 8-(quinoline-8-yldisulfanyl)quinolinium cations form dimers through π-π-stacking interaction between quinolinium rings. The reduced intramolecular interactions are observed between iodine - sulfur atoms and iodine-hydrogen atoms with shortened contacts (less of sum of van-der-waals contacts).

  5. 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. PMID:27442885

  6. Spectroscopic investigations on the interactions between isopropanol and trypsin at molecular level

    NASA Astrophysics Data System (ADS)

    Hu, Xinxin; Yu, Zehua; Liu, Rutao

    2013-05-01

    The toxicity of hydroxyl group of isopropanol to trypsin in aqueous solution was investigated by techniques including UV-visible absorption spectroscopy, fluorescence spectroscopy, circular dichroism (CD) spectroscopy, enzyme activity assay and molecular docking technology. The results of UV-visible absorption spectroscopy and CD spectra indicate that isopropanol could change the secondary structure of trypsin by increasing the content of α-helix and decreasing the content of β-sheet. The tertiary structure of trypsin was also changed owing to the loss of environmental asymmetry of amino acid residues. Isopropanol bound into a hydrophobic cavity on the surface of trypsin by a hydrogen bond located between the hydrogen atom on the hydroxyl of isopropanol and the oxygen atoms on SER 214 and hydrophobic interaction, as the molecular docking results showed. In addition, isopropanol could affect the function of trypsin by increasing its catalytic activity.

  7. 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

  8. The interaction between 4-aminoantipyrine and bovine serum albumin: multiple spectroscopic and molecular docking investigations.

    PubMed

    Teng, Yue; Liu, Rutao; Li, Chao; Xia, Qing; Zhang, Pengjun

    2011-06-15

    4-Aminoantipyrine (AAP) is widely used in the pharmaceutical industry, in biochemical experiments and in environmental monitoring. AAP as an aromatic pollutant in the environment poses a great threat to human health. To evaluate the toxicity of AAP at the protein level, the effects of AAP on bovine serum albumin (BSA) were investigated by multiple spectroscopic techniques and molecular modeling. After the inner filter effect was eliminated, the experimental results showed that AAP effectively quenched the intrinsic fluorescence of BSA via static quenching. The number of binding sites, the binding constant, the thermodynamic parameters and binding subdomain were measured, and indicated that AAP could spontaneously bind with BSA on subdomain IIIA through electrostatic forces. Molecular docking results revealed that AAP interacted with the Glu 488 and Glu 502 residues of BSA. Furthermore, the conformation of BSA was demonstrably changed in the presence of AAP. The skeletal structure of BSA loosened, exposing internal hydrophobic aromatic ring amino acids and peptide strands to the solution. PMID:21497437

  9. 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.

  10. Investigation of the interaction between amodiaquine and human serum albumin by fluorescence spectroscopy and molecular modeling.

    PubMed

    Samari, Fayezeh; Shamsipur, Mojtaba; Hemmateenejad, Bahram; Khayamian, Taghi; Gharaghani, Sajjad

    2012-08-01

    The interaction of amodiaquine (AQ) with human serum albumin (HSA) has been studied by fluorescence spectroscopy. Based on the sign and magnitude of the enthalpy and entropy changes (ΔH(0) = -43.27 kJ mol(-1) and ΔS(0) = -50.03 J mol(-1) K(-1)), hydrogen bond and van der Waals forces were suggested as the main interacting forces. Moreover, the efficiency of energy transfer and distance between HSA and acceptor AQ was calculated. Finally, the binding of AQ to HSA was modeled by molecular docking and molecular dynamic simulation methods. Excellent agreement was found between the experimental and theoretical results. Both experimental results and modeling methods suggested that AQ binds mainly to the sub-domain IIA of HSA. PMID:22658498

  11. 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

  12. 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

  13. 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. PMID:27068972

  14. 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

  15. 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

  16. Investigating the Interaction Pattern and Structural Elements of a Drug-Polymer Complex at the Molecular Level.

    PubMed

    Nie, Haichen; Mo, Huaping; Zhang, Mingtao; Song, Yang; Fang, Ke; Taylor, Lynne S; Li, Tonglei; Byrn, Stephen R

    2015-07-01

    Strong associations between drug and polymeric carriers are expected to contribute to higher drug loading capacities and better physical stability of amorphous solid dispersions. However, molecular details of the interaction patterns and underlying mechanisms are still unclear. In the present study, a series of amorphous solid dispersions of clofazimine (CLF), an antileprosy drug, were prepared with different polymers by applying the solvent evaporation method. When using hypromellose phthalate (HPMCP) as the carrier, the amorphous solid dispersion system exhibits not only superior drug loading capacity (63% w/w) but also color change due to strong drug-polymer association. In order to further explain these experimental observations, the interaction between CLF and HPMCP was investigated in a nonpolar volatile solvent system (chloroform) prior to forming the solid dispersion. We observed significant UV/vis and (1)H NMR spectral changes suggesting the protonation of CLF and formation of ion pairs between CLF and HPMCP in chloroform. Furthermore, nuclear Overhauser effect spectroscopy (NOESY) and diffusion order spectroscopy (DOSY) were employed to evaluate the strength of associations between drug and polymers, as well as the molecular mobility of CLF. Finally, by correlating the experimental values with quantum chemistry calculations, we demonstrate that the protonated CLF is binding to the carboxylate group of HPMCP as an ion pair and propose a possible structural model of the drug-polymer complex. Understanding the drug and carrier interaction patterns from a molecular perspective is critical for the rational design of new amorphous solid dispersions. PMID:25988812

  17. 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

  18. 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

  19. Atomic & Molecular Interactions

    SciTech Connect

    2002-07-12

    The Gordon Research Conference (GRC) on Atomic & Molecular Interactions was held at Roger Williams University, Bristol, RI. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  20. Investigation of the interaction between quercetin and human serum albumin by multiple spectra, electrochemical impedance spectra and molecular modeling.

    PubMed

    Dai, Jie; Zou, Ting; Wang, Li; Zhang, Yezhong; Liu, Yi

    2014-12-01

    Quercetin (Qu), a flavonoid compound, exists widely in the human diet and exhibits a variety of pharmacological activities. This work is aimed at studying the effect of Qu on the bioactive protein, human serum albumin (HSA) under simulated biophysical conditions. Multiple spectroscopic methods (including fluorescence and circular dichroism), electrochemical impedance spectra (EIS) and molecular modeling were employed to investigate the interaction between Qu and HSA. The fluorescence quenching and EIS experimental results showed that the fluorescence quenching of HSA was caused by formation of a Qu-HSA complex in the ground state, which belonged to the static quenching mechanism. Based on the calculated thermodynamic parameters, it concluded that the interaction was a spontaneous process and hydrogen bonds combined with van der Waal's forces played a major role in stabilizing the Qu-HSA complex. Molecular modeling results demonstrated that several amino acids participated in the binding process and the formed Qu-HSA complex was stabilized by H-bonding network at site I in sub-domain IIA, which was further confirmed by the site marker competitive experiments. The evidence from circular dichroism (CD) indicated that the secondary structure and microenvironment of HSA were changed. Alterations in the conformation of HSA were observed with a reduction in the amount of α helix from 59.9% (free HSA) to 56% (Qu-HSA complex), indicating a slight unfolding of the protein polypeptides. PMID:24801949

  1. 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

  2. Molecular interaction investigation between three CdTe:Zn(2+) quantum dots and human serum albumin: A comparative study.

    PubMed

    Huang, Shan; Qiu, Hangna; Liu, Yi; Huang, Chusheng; Sheng, Jiarong; Su, Wei; Xiao, Qi

    2015-12-01

    Water-soluble Zn-doped CdTe quantum dots (CdTe:Zn(2+) QDs) have attracted great attention in biological and biomedical applications. In particular, for any potential in vivo application, the interaction of CdTe:Zn(2+) QDs with human serum albumin (HSA) is of greatest importance. As a step toward the elucidation of the fate of CdTe:Zn(2+) QDs introduced to organism, the molecular interactions between CdTe:Zn(2+) QDs with three different sizes and HSA were systematically investigated by spectroscopic techniques. Three CdTe:Zn(2+) QDs with maximum emission of 514 nm (green QDs, GQDs), 578 nm (yellow QDs, YQDs), and 640 nm (red QDs, RQDs) were tested. The binding of CdTe:Zn(2+) QDs with HSA was a result of the formation of HSA-QDs complex and electrostatic interactions played major roles in stabilizing the complex. The Stern-Volmer quenching constant, associative binding constant, and corresponding thermodynamic parameters were calculated. The site-specific probe competitive experiments revealed that the binding location of CdTe:Zn(2+) QDs with HSA was around site I. The microenvironmental and conformational changes of HSA induced by CdTe:Zn(2+) QDs were analyzed. These results suggested that the conformational change of HSA was dramatically at secondary structure level and the biological activity of HSA was weakened in the present of CdTe:Zn(2+) QDs with bigger size. PMID:26555713

  3. Combined multispectroscopic and molecular docking investigation on the interaction between delphinidin-3-O-glucoside and bovine serum albumin.

    PubMed

    Zuo, Huijun; Tang, Lin; Li, Shu; Huang, Junwei

    2015-02-01

    Anthocyanin is one of the flavonoid phytopigments with specific health benefits. The interaction between delphinidin-3-O-glucoside (D3G) and bovine serum albumin (BSA) was investigated by fluorescence spectroscopy, synchronous fluorescence spectroscopy, three-dimensional fluorescence spectroscopy, ultraviolet-visible absorption spectroscopy, circular dichroism spectroscopy and molecular modeling. D3G effectively quenched the intrinsic fluorescence of BSA via static quenching. The number of binding sites and binding constant Ka were determined, and the hydrogen bonds and van der Waals forces played major roles in stabilizing the D3G-BSA complex. The distance r between donor and acceptor was obtained as 2.81 nm according to Förster's theory. In addition, the effects of pH and metal ions on the binding constants were discussed. The results studied by synchronous fluorescence, three-dimensional fluorescence and circular dichroism experiments indicated that the secondary structures of the protein has been changed by the addition of D3G and the α-helix content of BSA decreased (from 56.1% to 52.4%). Furthermore, the study of site marker competitive experiments and molecular modeling indicated that D3G could bind to site I of BSA, which was in the large hydrophobic cavity of subdomain IIA. PMID:24891226

  4. Supramolecular interactions of nonsteroidal anti-inflammatory drug in nanochannels of molecular containers: a spectroscopic, thermogravimetric and microscopic investigation.

    PubMed

    Maity, Banibrata; Chatterjee, Aninda; Ahmed, Sayeed Ashique; Seth, Debabrata

    2014-11-10

    Supramolecular host-guest complexation between the nonsteroidal anti-inflammatory drug indomethacin (IMC) and molecular containers were investigated. The weakly fluorescent drug molecule becomes highly fluorescent on complexation with different molecular containers, and time-resolved fluorescence emission spectroscopy reveals that the lifetime components of IMC significantly increase in the presence of molecular containers, compared with the lifetimes in neat water. The respective solid host-guest complexes were synthesised and characterised by Fourier transform infrared and (1) H nuclear magnetic resonance spectroscopic analysis. Microscopy techniques were used to analyse modifications of the surface morphology, owing to the formation of supramolecular complexes. The effect of the molecular container on the optical properties of IMC has also been investigated to determine the effect of nanochannels of different size and structure. PMID:25146319

  5. 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.

  6. 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. PMID:25787898

  7. Investigations on the interactions of diclofenac sodium with HSA and ctDNA using molecular modeling and multispectroscopic methods

    NASA Astrophysics Data System (ADS)

    Cui, Yanrui; Hao, Erjun; Hui, Guangquan; Guo, Wei; Cui, Fengling

    2013-06-01

    A tentative study on interaction of diclofenac sodium (DF-Na) with human serum albumin (HSA) and calf thymus DNA (ctDNA) was conducted by using multi-spectroscopic and molecular modeling techniques under simulative physiological conditions. The results of spectroscopic measurements suggested that the quenching mechanisms were static quenching. Three-dimensional fluorescence spectroscopy clearly demonstrated the occurrence of conformational changes of HSA with addition of DF-Na. In addition, competitive studies with ethidium bromide (EB) have shown that DF-Na can bind to ctDNA relatively strong via groove binding. Based on the values of thermodynamic parameters and the results of molecular modeling, it was confirmed that hydrophobic forces and hydrogen bond were the mainly binding forces in DF-Na-HSA and DF-Na-DNA systems. The binding distance between DF-Na and HSA was also determined using the theory of the Förster energy transference.

  8. 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.

  9. Probing the interaction of a therapeutic flavonoid, pinostrobin with human serum albumin: multiple spectroscopic and molecular modeling investigations.

    PubMed

    Feroz, Shevin R; Mohamad, Saharuddin B; Bakri, Zarith S D; Malek, Sri N A; Tayyab, Saad

    2013-01-01

    Interaction of a pharmacologically important flavonoid, pinostrobin (PS) with the major transport protein of human blood circulation, human serum albumin (HSA) has been examined using a multitude of spectroscopic techniques and molecular docking studies. Analysis of the fluorescence quenching data showed a moderate binding affinity (1.03 × 10(5) M(-1) at 25°C) between PS and HSA with a 1∶1 stoichiometry. Thermodynamic analysis of the binding data (ΔS = +44.06 J mol(-1) K(-1) and ΔH = -15.48 kJ mol(-1)) and molecular simulation results suggested the involvement of hydrophobic and van der Waals forces, as well as hydrogen bonding in the complex formation. Both secondary and tertiary structural perturbations in HSA were observed upon PS binding, as revealed by intrinsic, synchronous, and three-dimensional fluorescence results. Far-UV circular dichroism data revealed increased thermal stability of the protein upon complexation with PS. Competitive drug displacement results suggested the binding site of PS on HSA as Sudlow's site I, located at subdomain IIA, and was well supported by the molecular modelling data. PMID:24116089

  10. Probing the Interaction of a Therapeutic Flavonoid, Pinostrobin with Human Serum Albumin: Multiple Spectroscopic and Molecular Modeling Investigations

    PubMed Central

    Feroz, Shevin R.; Mohamad, Saharuddin B.; Bakri, Zarith S. D.; Malek, Sri N. A.; Tayyab, Saad

    2013-01-01

    Interaction of a pharmacologically important flavonoid, pinostrobin (PS) with the major transport protein of human blood circulation, human serum albumin (HSA) has been examined using a multitude of spectroscopic techniques and molecular docking studies. Analysis of the fluorescence quenching data showed a moderate binding affinity (1.03 × 105 M−1 at 25°C) between PS and HSA with a 1∶1 stoichiometry. Thermodynamic analysis of the binding data (ΔS = +44.06 J mol−1 K−1 and ΔH = −15.48 kJ mol−1) and molecular simulation results suggested the involvement of hydrophobic and van der Waals forces, as well as hydrogen bonding in the complex formation. Both secondary and tertiary structural perturbations in HSA were observed upon PS binding, as revealed by intrinsic, synchronous, and three-dimensional fluorescence results. Far-UV circular dichroism data revealed increased thermal stability of the protein upon complexation with PS. Competitive drug displacement results suggested the binding site of PS on HSA as Sudlow’s site I, located at subdomain IIA, and was well supported by the molecular modelling data. PMID:24116089

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

    PubMed Central

    Bai, Qifeng; Yao, Xiaojun

    2016-01-01

    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. PMID:26887338

  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. 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. PMID:24702936

  14. 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

  15. Molecular dynamics investigation of the interaction of an edge dislocation with Frank loops in Fe-Ni10-Cr20 alloy

    NASA Astrophysics Data System (ADS)

    Baudouin, Jean-Baptiste; Nomoto, Akiyoshi; Perez, Michel; Monnet, Ghiath; Domain, Christophe

    2015-10-01

    The inhibition of dislocations motion by irradiation-induced defects, such as dislocation loops, is one of the main mechanisms of irradiation hardening of austenitic stainless steels. In this work, Molecular Dynamics (MD) simulations of interaction between an edge dislocation and Frank loops in Fe-Ni10-Cr20 ternary alloy mimicking austenitic stainless steels are carried out to investigate and model dislocation behavior. An empirical interatomic potential developed recently for a ternary FeNiCr system is used for the MD calculations. The interactions are calculated at different temperatures, loop orientations, loop size and solute atom configurations. The results show that the loop strength and the interaction processes depend on the solute atom configuration, the geometrical configurations between the dislocation and the loop and temperature. It is also demonstrated that a small Frank loop is not so weak an obstacle in the alloy. The interaction leads microstructural change such as loop shearing, loop unfaulting and loop absorption in the dislocation. In the former two cases, the loop remains after the interaction, however in some cases an absorption of the remaining loop by subsequent interactions with successive dislocations is observed.

  16. 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.

  17. Topology of molecular interaction networks.

    PubMed

    Winterbach, Wynand; Van Mieghem, Piet; Reinders, Marcel; Wang, Huijuan; de Ridder, Dick

    2013-01-01

    Molecular interactions are often represented as network models which have become the common language of many areas of biology. Graphs serve as convenient mathematical representations of network models and have themselves become objects of study. Their topology has been intensively researched over the last decade after evidence was found that they share underlying design principles with many other types of networks.Initial studies suggested that molecular interaction network topology is related to biological function and evolution. However, further whole-network analyses did not lead to a unified view on what this relation may look like, with conclusions highly dependent on the type of molecular interactions considered and the metrics used to study them. It is unclear whether global network topology drives function, as suggested by some researchers, or whether it is simply a byproduct of evolution or even an artefact of representing complex molecular interaction networks as graphs.Nevertheless, network biology has progressed significantly over the last years. We review the literature, focusing on two major developments. First, realizing that molecular interaction networks can be naturally decomposed into subsystems (such as modules and pathways), topology is increasingly studied locally rather than globally. Second, there is a move from a descriptive approach to a predictive one: rather than correlating biological network topology to generic properties such as robustness, it is used to predict specific functions or phenotypes.Taken together, this change in focus from globally descriptive to locally predictive points to new avenues of research. In particular, multi-scale approaches are developments promising to drive the study of molecular interaction networks further. PMID:24041013

  18. Topology of molecular interaction networks

    PubMed Central

    2013-01-01

    Molecular interactions are often represented as network models which have become the common language of many areas of biology. Graphs serve as convenient mathematical representations of network models and have themselves become objects of study. Their topology has been intensively researched over the last decade after evidence was found that they share underlying design principles with many other types of networks. Initial studies suggested that molecular interaction network topology is related to biological function and evolution. However, further whole-network analyses did not lead to a unified view on what this relation may look like, with conclusions highly dependent on the type of molecular interactions considered and the metrics used to study them. It is unclear whether global network topology drives function, as suggested by some researchers, or whether it is simply a byproduct of evolution or even an artefact of representing complex molecular interaction networks as graphs. Nevertheless, network biology has progressed significantly over the last years. We review the literature, focusing on two major developments. First, realizing that molecular interaction networks can be naturally decomposed into subsystems (such as modules and pathways), topology is increasingly studied locally rather than globally. Second, there is a move from a descriptive approach to a predictive one: rather than correlating biological network topology to generic properties such as robustness, it is used to predict specific functions or phenotypes. Taken together, this change in focus from globally descriptive to locally predictive points to new avenues of research. In particular, multi-scale approaches are developments promising to drive the study of molecular interaction networks further. PMID:24041013

  19. 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…

  20. 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

  1. Steady-state kinetic investigation of cytochrome P450cam: interaction with redox partners and reaction with molecular oxygen.

    PubMed

    Purdy, Matthew M; Koo, Laura S; Ortiz de Montellano, Paul R; Klinman, Judith P

    2004-01-13

    Cytochrome P450cam (CYP101) is a prokaryotic monooxygenase that requires two proteins, putidaredoxin reductase (PdR) and putidaredoxin (Pdx), to supply electrons from NADH. This study addresses the mechanism by which electrons are transported from PdR to P450cam through Pdx and used to activate O(2) at the heme of P450cam. It is shown that k(cat)/Km(O2) is independent of the PdR concentration and hyperbolically dependent on Pdx. The phenomenon of saturation of reaction rates with either P450cam or PdR at high ratios of one enzyme to the other is investigated and shown to be consistent with a change in the rate limiting step. Either the reduction of Pdx by PdR (high P450) or the reduction of P450 by Pdx (high PdR) determines the rate. These data support a mechanism where Pdx acts as a shuttle for transport of electrons from PdR to P450cam, effectively ruling out the formation of a kinetically significant PdR/Pdx/P450cam complex. PMID:14705955

  2. Techniques for Investigating Molecular Toxicology of Nanomaterials.

    PubMed

    Wang, Yanli; Li, Chenchen; Yao, Chenjie; Ding, Lin; Lei, Zhendong; Wu, Minghong

    2016-06-01

    Nanotechnology has been a rapidly developing field in the past few decades, resulting in the more and more exposure of nanomaterials to human. The increased applications of nanomaterials for industrial, commercial and life purposes, such as fillers, catalysts, semiconductors, paints, cosmetic additives and drug carriers, have caused both obvious and potential impacts on human health and environment. Nanotoxicology is used to study the safety of nanomaterials and has grown at the historic moment. Molecular toxicology is a new subdiscipline to study the interactions and impacts of materials at the molecular level. To better understand the relationship between the molecular toxicology and nanomaterials, this review summarizes the typical techniques and methods in molecular toxicology which are applied when investigating the toxicology of nanomaterials and include six categories: namely; genetic mutation detection, gene expression analysis, DNA damage detection, chromosomal aberration analysis, proteomics, and metabolomics. Each category involves several experimental techniques and methods. PMID:27319209

  3. Spin vibronics in interacting nonmagnetic molecular nanojunctions

    NASA Astrophysics Data System (ADS)

    Weiss, S.; Brüggemann, J.; Thorwart, M.

    2015-07-01

    We show that in the presence of ferromagnetic electronic reservoirs and spin-dependent tunnel couplings, molecular vibrations in nonmagnetic single molecular transistors induce an effective intramolecular exchange magnetic field. It generates a finite spin accumulation and precession for the electrons confined on the molecular bridge and occurs under (non)equilibrium conditions. The effective exchange magnetic field is calculated here to lowest order in the tunnel coupling for a nonequilibrium transport setup. Coulomb interaction between electrons is taken into account as well as a finite electron-phonon coupling. We show that for realistic physical parameters, an effective spin-phonon coupling emerges. It is induced by quantum many-body interactions, which are either of electron-phonon or Coulomb type. We investigate the precession and accumulation of the confined spins as function of bias and gate voltages as well as their dependence on the angle enclosed by the magnetizations between the left and right reservoir.

  4. 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

  5. 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. PMID:26286009

  6. 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. PMID:27377760

  7. 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

  8. 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.

  9. Molecular simulation investigation on the interaction between barrier-to-autointegration factor dimer or its Gly25Glu mutant and LEM domain of emerin.

    PubMed

    Shang, Yu-Dong; Zhang, Ji-Long; Wang, Yan; Zhang, Hong-Xing; Zheng, Qing-Chuan

    2014-11-01

    The interaction between barrier-to-autointegration factor dimer (BAF2) and LEM domain of emerin (Em(LEM)) was studied by molecular simulation methods. Nonspecific fragment of double-strand DNA molecule was docked with each chain of BAF2 by ZDOCK program. The model of DNA2:BAF2:Em(LEM) was thus constructed. The mutant Gly25Glu of BAF2 was manually constructed to explore the detailed effect of the mutation on the binding of BAF2 and Em(LEM). It has been experimentally suggested that point mutation Gly25Glu can disturb the binding between BAF2 and Em(LEM). Then, molecular dynamics (MD) simulations were performed on DNA2:BAF2(WT):Em(LEM) and DNA2:BAF2(MT):Em(LEM) complexes. 30ns trajectories revealed that the trajectory fluctuations of MT complex are more violent than that of the WT complex. Further, the binding free energy analysis showed that the electronegative residues Asp57, Glu61 and Asp65 from chain A, glu36 from chain B of BAF2 mainly contribute to interact with Em(LEM). Besides, a stable π-π stack between trp62 and phe39 from BAF2(WT) chain B is destroyed by Glu25 in BAF2(MT). As a result, trp62 forms an interaction with glu25, and phe39 converts to strengthen affinity to Em(LEM). On the other hand, Trp62 from chain A also forms a strong interaction with MT Glu25. Thus, with the docking of DNA, BAF2(MT) has higher affinity with Em(LEM) than BAF2(WT). PMID:25462326

  10. 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

  11. 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

  12. Fluorescence spectroscopy investigation and molecular docking simulation of the interaction of β-lactoglobulin A (BLGA) with meso-tetrakis(4-sulfonatophenyl) porphyrin (TSPP)

    NASA Astrophysics Data System (ADS)

    Silva, Ivan; Brancaleon, Lorenzo; Sansone, Sam

    2008-03-01

    The interaction of TSPP and β-lactoglobulin A (BLGA) was studied as a function of pH (6.0-9.0). TSPP is a dye that is currently in clinical trials for its application in photodynamic therapy of cancer, and BLGA is a well known globular protein. Binding to the protein affects the photophysics of the dye, hence its potential in clinical applications. Data from TSPP fluorescence experiments were analyzed and modeled by computational methods. Protein-dye interaction was studied using fluorescence spectroscopy to record the spectral shift (from 643nm to 649nm) to quantify bound and free dye with use of Gaussian curve fitting. TSPP-induced quenching of protein fluorescence determined the binding constant and the number of binding sites through S-V and double-log plots. Fluorescence lifetime characterized the effects of the binding and the location of the binding site through FRET. Unlike the binding of protoporphyrin IX, pH dependence of the TSPP binding to BLG is not modulated by the pH conformational change of the protein. Molecular simulation of the docking of TSPP monomers to BLGA dimers were done using the Arguslab software. Simulations reveal that the interaction is driven by the four negative charges on TSPP which keep it on the surface of the protein.

  13. 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…

  14. Theoretical analysis of dynamic processes for interacting molecular motors

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

    Biological transport is supported by the 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 carrying out an analysis of a new class of totally asymmetric exclusion processes, in which interactions are accounted for in a thermodynamically consistent fashion. This allows us to explicitly connect microscopic features of motor proteins with their collective dynamic properties. A theoretical analysis that combines various mean-field calculations and computer simulations suggests that the dynamic properties of molecular motors strongly depend on the interactions, and that the 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 motor transport is more sensitive to attractive interactions. Applications of these results for kinesin motor proteins are discussed.

  15. 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.

  16. Molecular level investigation on the interaction of pluronic F127 and human intestinal bile salts using excited state prototropism of 1-naphthol.

    PubMed

    Swain, Jitendriya

    2016-07-01

    Pluronic F127 (PF127), a surfactant polymer is used as a drug delivery system and has been introduced recently in the food research to delay lipid digestion process. In this context study the interaction of this polymer with human intestinal bile salts assumes important. The studies involving interaction of PF127 with human intestinal bile salts sodium taurocholic acid (NaTC) and sodium cholate acid (NaC) by using differential scanning calorimetry (DSC) and 1-naphthol as a fluorescent molecular probe show that the bile salts induce decrease of sol-gel phase transition temperature of the PF127 to lower temperature, from ~21°C to ~18°C. Variation of neutral form fluorescence intensity of 1-naphthol with bile salts in water confirmed efficient micellar aggregation with critical micellar concentration (CMC) values of 12.6mM for NaTC and 12.7mM for NaC. Fluorescence parameters like fluorescence intensity and fluorescence lifetime of the two excited state prototropic forms {neutral form emission (λem=370nm), anion form emission (λem=470nm)} of 1-naphthol suggested that the NaTC (below critical micellar concentration 12mM) and NaC (above critical micellar concentration 12mM) induce appreciable dehydration of the hydrophilic corona as well as core region PF127 hydrogel. The micropolarity of the hydrogel microenvironment decreases with increase in concentration of both the bile salts. PMID:27093000

  17. 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.

  18. 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.

  19. Coupling between side chain interactions and binding pocket flexibility in HLA-B*44:02 molecules investigated by molecular dynamics simulations.

    PubMed

    Ostermeir, Katja; Springer, Sebastian; Zacharias, Martin

    2015-02-01

    MHC class I molecules present antigenic peptides to cytotoxic T-cells at the cell surface. Peptide loading of class I molecules in the endoplasmatic reticulum can involve interaction with the tapasin chaperone protein. The human class I allotype HLA-B*44:02 with an Asp at position 116 at the floor of the F pocket (which binds the peptide C-terminal residues) depends on tapasin for efficient peptide loading. However, HLA-B*44:05 (identical to B*44:02 except for tyrosine 116) can efficiently load peptides in the absence of tapasin. Both allotypes adopt very similar structures in the presence of the same peptide. Molecular dynamics simulations indicate a significantly higher conformational flexibility of the F pocket in the absence of a peptide for B*44:02 compared to B*44:05. Free energy simulations to open the F pocket indicate a molecular side chain switch mechanism that underlies the global opening motion. This side chain switch involves the rearrangement of salt bridges and hydrogen bonding of the basic arginine 97 with three acidic aspartate residues 114, 116 and 156 near the F pocket. A replica exchange simulation to specifically accelerate side chain motions demonstrates that the same side chain rearrangements induce global opening motions of the F pocket. In case of B*44:05 the free energy barrier for F pocket opening was significantly higher compared to B*44:02 and no associated side chain rearrangement was observed. Such coupling of local side chain rearrangements with global conformational changes might be the basis for allosteric changes in other class I allotypes as well as for allosteric changes in other proteins. PMID:25146482

  20. 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

  1. 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. PMID:24773576

  2. Molecular docking investigation of the binding interactions of macrocyclic inhibitors with HCV NS3 protease and its mutants (R155K, D168A and A156V).

    PubMed

    Ezat, Ahmed A; El-Bialy, Nihal S; Mostafa, Hamdy I A; Ibrahim, Medhat A

    2014-02-01

    Hepatitis C Virus (HCV) non-structural protein 3 (NS3) protease drug resistance poses serious challenges on the design of an effective treatment. Substrate Envelope Hypothesis, "the substrates of HCV NS3/4A protease have a consensus volume inside the active site called substrate envelope" is used to design potent and specific drugs to overcome this problem. Using molecular docking, we studied the binding interaction of the different inhibitors and protein and evaluated the effect of three different mutations (R155K, D168A and A156V) on the binding of inhibitors. P2-P4 macrocycles of 5A/5B and modified 5A/5B hexapeptide sequences have the best scores against the wild-type protein -204.506 and -206.823 kcal/mole, respectively. Also, charged P2-P4 macrocycles of 3/4A and 4A/4B hexapeptide sequences have low scores with the wild-type protein -200.467 and -203.186 kcal/mole, respectively. R155K mutation greatly affects the conformation of the compounds inside the active site. It inverts its orientations, and this is because the large and free side chain of K155 which restricts the conformation of the large P2-P4 macrocycle. The conformation of charged P2-P4 macrocycle of 3/4A hexapeptide sequence in wild-type, A156V and D168A proteins is nearly equal; while that of charged P2-P4 macrocycle of 4A/4B hexapeptide sequence is different. Nevertheless, these compounds have a slight increase of Van der Waals volume compared to that of substrates, they are potent against mutations and have good scores. Therefore, the suggested drugs can be used as an effective treatment solving HCV NS3/4A protease drug resistance problem. PMID:24374429

  3. 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.

  4. Multiple interactions between molecular and supramolecular ordering

    NASA Astrophysics Data System (ADS)

    Manno, M.; Emanuele, A.; Martorana, V.; Bulone, D.; San Biagio, P. L.; Palma-Vittorelli, M. B.; Palma, M. U.

    1999-02-01

    We report studies of the interplay among processes of molecular conformational changes, spinodal demixing of the solution, and molecular crosslinking involved in the physical gelation of a biopolysaccharide-water system. Multiple interactions and kinetic competition among these processes were studied under largely different absolute and relative values of their individual rates by appropriate choices of the quenching temperature at constant polymer concentration. Quenching temperature strongly affects the rate of growth but not the final value of the fractal dimension of the gel. Kinetic competition plays a central role in determining the final conformation of individual molecules and the structure and properties of the final gel. This behavior highlights the frustrated nature of the system, and the need of bringing kinetics sharply into focus in gelation theories. General aspects of the present findings and, specifically, the interplay of molecular conformation changes, solution demixing, and molecular crosslinking extend the relevance of these studies to the fast growing field of amyloid condensation and Prion diseases.

  5. A molecular beam scattering investigation of methanol-noble gas complexes: Characterization of the isotropic potential and insights into the nature of the interaction

    NASA Astrophysics Data System (ADS)

    Cappelletti, D.; Candori, P.; Falcinelli, S.; Albertí, M.; Pirani, F.

    2012-08-01

    Integral cross section experiments involving rotationally hot CH3OH projectiles and noble gas (Ng = Ne, Ar, Kr and Xe) targets are reported for the first time. Measured data have been exploited to characterize the phenomenological radial interaction in the CH3OH-Ng weakly bound complexes. Potential energy surfaces for all the systems have been formulated on the basis of a pairwise additive multicenter model. The comparison of model predictions with the most relevant experimental findings suggests that in CH3OH-Ng complexes, at variance with the behavior of the analogous complexes involving water or ammonia, the interaction is mainly due to van der Waals and induction components.

  6. Michigan molecular interactions r2: from interacting proteins to pathways.

    PubMed

    Tarcea, V Glenn; Weymouth, Terry; Ade, Alex; Bookvich, Aaron; Gao, Jing; Mahavisno, Vasudeva; Wright, Zach; Chapman, Adriane; Jayapandian, Magesh; Ozgür, Arzucan; Tian, Yuanyuan; Cavalcoli, Jim; Mirel, Barbara; Patel, Jignesh; Radev, Dragomir; Athey, Brian; States, David; Jagadish, H V

    2009-01-01

    Molecular interaction data exists in a number of repositories, each with its own data format, molecule identifier and information coverage. Michigan molecular interactions (MiMI) assists scientists searching through this profusion of molecular interaction data. The original release of MiMI gathered data from well-known protein interaction databases, and deep merged this information while keeping track of provenance. Based on the feedback received from users, MiMI has been completely redesigned. This article describes the resulting MiMI Release 2 (MiMIr2). New functionality includes extension from proteins to genes and to pathways; identification of highlighted sentences in source publications; seamless two-way linkage with Cytoscape; query facilities based on MeSH/GO terms and other concepts; approximate graph matching to find relevant pathways; support for querying in bulk; and a user focus-group driven interface design. MiMI is part of the NIH's; National Center for Integrative Biomedical Informatics (NCIBI) and is publicly available at: http://mimi.ncibi.org. PMID:18978014

  7. 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…

  8. 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.

  9. Molecular Mediators Governing Iron-Copper Interactions

    PubMed Central

    Gulec, Sukru; Collins, James F.

    2015-01-01

    Given their similar physiochemical properties, it is a logical postulate that iron and copper metabolism are intertwined. Indeed, iron-copper interactions were first documented over a century ago, but the homeostatic effects of one on the other has not been elucidated at a molecular level to date. Recent experimental work has, however, begun to provide mechanistic insight into how copper influences iron metabolism. During iron deficiency, elevated copper levels are observed in the intestinal mucosa, liver, and blood. Copper accumulation and/or redistribution within enterocytes may influence iron transport, and high hepatic copper may enhance biosynthesis of a circulating ferroxidase, which potentiates iron release from stores. Moreover, emerging evidence has documented direct effects of copper on the expression and activity of the iron-regulatory hormone hepcidin. This review summarizes current experimental work in this field, with a focus on molecular aspects of iron-copper interplay and how these interactions relate to various disease states. PMID:24995690

  10. 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

  11. 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.

  12. 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...

  13. 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

  14. 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

  15. Controlling single-molecule junction conductance by molecular interactions.

    PubMed

    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

  16. Investigating Evolutionary Questions Using Online Molecular Databases.

    ERIC Educational Resources Information Center

    Puterbaugh, Mary N.; Burleigh, J. Gordon

    2001-01-01

    Recommends using online molecular databases as teaching tools to illustrate evolutionary questions and concepts while introducing students to public molecular databases. Provides activities in which students make molecular comparisons between species. (YDS)

  17. 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.

  18. 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.

  19. Dispersion Interactions in High-Density Molecular Crystals

    NASA Astrophysics Data System (ADS)

    Csernica, Peter; Maitra, Rahul; Distasio, Robert

    Dispersion interactions are ubiquitous quantum mechanical phenomena arising from correlated electron density fluctuations in molecules and materials. As a key component of non-bonded interactions, dispersion forces play a critical role in determining the structure and stability of molecular crystals. Due to the relative intermolecular separation in high-density molecular crystals, an accurate description of these non-bonded interactions requires the inclusion of terms beyond the asymptotic induced-dipole-induced-dipole (C6 /R6) contribution. In this work, we have developed a first principles based approach within the framework of Density Functional Theory (i.e., that only depends on the charge density n (r)) for capturing the higher-order induced multipolar contributions to the correlation energy. As a first application of this method, we have investigated the structure and stability of the high-density ice molecular crystal polymorphs at the ice VI--ice VII--ice VIII triple point (278K, 2.1GPa) using ab-initio molecular dynamics in the isobaric-isothermal (NpT) ensemble.

  20. Fanconi anemia proteins and their interacting partners: a molecular puzzle.

    PubMed

    Kaddar, Tagrid; Carreau, Madeleine

    2012-01-01

    In recent years, Fanconi anemia (FA) has been the subject of intense investigations, primarily in the DNA repair research field. Many discoveries have led to the notion of a canonical pathway, termed the FA pathway, where all FA proteins function sequentially in different protein complexes to repair DNA cross-link damages. Although a detailed architecture of this DNA cross-link repair pathway is emerging, the question of how a defective DNA cross-link repair process translates into the disease phenotype is unresolved. Other areas of research including oxidative metabolism, cell cycle progression, apoptosis, and transcriptional regulation have been studied in the context of FA, and some of these areas were investigated before the fervent enthusiasm in the DNA repair field. These other molecular mechanisms may also play an important role in the pathogenesis of this disease. In addition, several FA-interacting proteins have been identified with roles in these "other" nonrepair molecular functions. Thus, the goal of this paper is to revisit old ideas and to discuss protein-protein interactions related to other FA-related molecular functions to try to give the reader a wider perspective of the FA molecular puzzle. PMID:22737580

  1. Molecular dynamics investigation of nanoscale cavitation dynamics

    NASA Astrophysics Data System (ADS)

    Sasikumar, Kiran; Keblinski, Pawel

    2014-12-01

    We use molecular dynamics simulations to investigate the cavitation dynamics around intensely heated solid nanoparticles immersed in a model Lennard-Jones fluid. Specifically, we study the temporal evolution of vapor nanobubbles that form around the solid nanoparticles heated over ps time scale and provide a detail description of the following vapor formation and collapse. For 8 nm diameter nanoparticles we observe the formation of vapor bubbles when the liquid temperature 0.5-1 nm away from the nanoparticle surface reaches ˜90% of the critical temperature, which is consistent with the onset of spinodal decomposition. The peak heat flux from the hot solid to the surrounding liquid at the bubble formation threshold is ˜20 times higher than the corresponding steady state critical heat flux. Detailed analysis of the bubble dynamics indicates adiabatic formation followed by an isothermal final stage of growth and isothermal collapse.

  2. Enlightening molecular mechanisms through study of protein interactions

    PubMed Central

    Rizo, Josep; Rosen, Michael K.; Gardner, Kevin H.

    2012-01-01

    The investigation of molecular mechanisms is a fascinating area of current biological research that unites efforts from scientists with very diverse expertise. This review provides a perspective on the characterization of protein interactions as a central aspect of this research. We discuss case studies on the neurotransmitter release machinery that illustrate a variety of principles and emphasize the power of combining nuclear magnetic resonance (NMR) spectroscopy with other biophysical techniques, particularly X-ray crystallography. These studies have shown that: (i) the soluble SNAP receptor (SNARE) proteins form a tight complex that brings the synaptic vesicle and plasma membranes together, which is key for membrane fusion; (ii) the SNARE syntaxin-1 adopts an autoinhibitory closed conformation; (iii) Munc18-1 plays crucial functions through interactions with closed syntaxin-1 and with the SNARE complex; (iv) Munc13s mediate the opening of syntaxin-1; (v) complexins play dual roles through distinct interactions with the SNARE complex; (vi) synaptotagmin-1 acts a Ca2+ sensor, interacting simultaneously with the membranes and the SNAREs; and (vii) a Munc13 homodimer to Munc13-RIM heterodimer switch modulates neurotransmitter release. Overall, this research underlines the complexities involved in elucidating molecular mechanisms and how these mechanisms can depend critically on an interplay between strong and weak protein interactions. PMID:22735643

  3. 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.

  4. Many-Body Dispersion Interactions in Molecular Materials

    NASA Astrophysics Data System (ADS)

    Distasio, Robert A., Jr.

    2015-03-01

    In this work, we have developed an efficient method for obtaining an accurate theoretical description of van der Waals (vdW) interactions that includes both long-range Coulomb electrodynamic response screening effects as well as treatment of the many-body vdW energy to infinite order. This method goes beyond the standard C6 /R6 pairwise additive approximation and can easily be coupled to a wide array of theoretical methods, ranging from classical force fields to higher-level quantum chemical calculations. To demonstrate the increasingly important role played by many-body vdW interactions in large, structurally complex molecular systems, we use this method to investigate several pertinent molecular properties, such as binding energies/affinities in gas-phase molecular dimers and supramolecular complexes, relative conformational energetics in small polypeptides, and thermodynamic stabilities among competing molecular crystal polymorphs. This work received funding from the Department of Energy under Grant Nos.: DOE DE-SC0008626 and DOE DE-FG02ER46201 and the European Research Council (ERC Starting Grant VDW-CMAT).

  5. 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

  6. 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

  7. Molecular Recognition and Specific Interactions for Biosensing Applications

    PubMed Central

    Kim, Dong Chung; Kang, Dae Joon

    2008-01-01

    Molecular recognition and specific interactions are reliable and versatile routes for site-specific and well-oriented immobilization of functional biomolecules on surfaces. The control of surface properties via the molecular recognition and specific interactions at the nanoscale is a key element for the nanofabrication of biosensors with high sensitivity and specificity. This review intends to provide a comprehensive understanding of the molecular recognition- and specific interaction-mediated biosensor fabrication routes that leads to biosensors with well-ordered and controlled structures on both nanopatterned surfaces and nanomaterials. Herein self-assembly of the biomolecules via the molecular recognition and specific interactions on nanoscaled surfaces as well as nanofabrication techniques of the biomolecules for biosensor architecture are discussed. We also describe the detection of molecular recognition- and specific interaction-mediated molecular binding as well as advantages of nanoscale detection.

  8. Interactive Data Mining for Molecular Graphs

    PubMed Central

    Yılmaz, Burcu; Göktürk, Mehmet

    2009-01-01

    Designing new medical drugs for a specific disease requires extensive analysis of many molecules that have an activity for the disease. The main goal of these extensive analyses is to discover substructures (fragments) that account for the activity of these molecules. Once they are discovered, these fragments are used to understand the structure of new drugs and design new medicines for the disease. In this paper, we propose an interactive approach for visual molecule mining to discover fragments of molecules that are responsible for the desired activity with respect to a specific disease. Our approach visualizes molecular data in a form that can be interpreted by a human expert. Using a pipelining structure, it enables experts to contribute to the solution with their expertise at different levels. In order to derive desired fragments, it combines histogram-based filtering and clustering methods in a novel way. This combination enables a flexible determination of frequent fragments that repeat in molecules exactly or with some variations. PMID:20052387

  9. Single Molecular Film for Recognizing Biological Molecular Interaction: DNA-Protein Interaction and Enzyme Reaction

    NASA Astrophysics Data System (ADS)

    Kurihara, Kazue

    Protein-protein and protein-substrate interactions play essential roles in biological functions. Surface forces measurement and atomic force microscopy, which directly measure the interaction forces as a function of the surface separation, enable us to quantitatively evaluate these interactions [1-3]. We have employed the surface forces measurement [4] and colloidal probe atomic force microscopy [5] to study interactions involved in specific molecular recognition of DNA-protein and enzyme-substrate reaction. Studied are interactions between nucleic acid bases (adenine and thymine) [6], Spo0A-DB (the DNA-binding site of a transcription factor Spo0A), and DNA [7,8], those between subunits I and II of heptaprenyl diphosphate (HepPP) synthase in the presence of a substrate ((E,E)-farnesyl diphosphate, FPP) and a cofactor (Mg2+) [9-11], and the selectivity of the substrates in this enzymatic reaction [12]. Keys of our approach are the preparation of well-defined samples and the appropriate analysis. We have modified he substrate surfaces with these proteins using the Langmuir-Blodgett (LB) method. This chapter reviews the LB modification method and subsequent demonstrations of biological specific interactions employing this approach.

  10. 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.

  11. Investigation of Dendrimer-Membrane Interactions

    NASA Astrophysics Data System (ADS)

    Mecke, Almut; Hessler, Jessica; Lee, Inhan; Banaszak Holl, Mark; Orr, Bradford; Patri, Anil K.; Baker, J. R.

    2003-03-01

    Modified Polyamidoamine (PAMAM) dendrimers show great promise as targeted drug transport agents. Current research efforts point to the possibility of dramatic improvements to conventional chemotherapy by selectively delivering a therapeutic to antigen bearing tumor cells. In order to better understand the uptake mechanism of such devices into cells we are investigating dendrimer-surface adsorption and dendrimer-membrane interactions using atomic force microscopy, light scattering and computer simulations. Model systems consisting of supported DMPC lipid bilayers have shown interesting results suggesting the shape and architecture of nano-devices play an important role for their biologic activity. We are also investigating the effect of targeted drug vehicles on cells in vitro.

  12. 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

  13. Intramolecular and Intermolecular Interactions in Hybrid Organic-Inorganic Alucone Films Grown by Molecular Layer Deposition.

    PubMed

    Park, Yi-Seul; Kim, Hyein; Cho, Boram; Lee, Chaeyun; Choi, Sung-Eun; Sung, Myung Mo; Lee, Jin Seok

    2016-07-13

    Investigation of molecular interactions in polymeric films is crucial for understanding and engineering multiscale physical phenomena correlated to device function and performance, but this often involves a compromise between theoretical and experimental data, because of poor film uniformity. Here, we report the intramolecular and intermolecular interactions inside the ultrathin and conformal hybrid organic-inorganic alucone films grown by molecular layer deposition, based on sequential and self-limiting surface reactions. Varying the carbon chain length of organic precursors, which affects their molecular flexibility, caused intramolecular interactions such as double reactions by bending of the molecular backbone, resulting in formation of hole vacancies in the films. Furthermore, intermolecular interactions in alucone polymeric films are dependent on the thermal kinetics of molecules, leading to binding failures and cross-linking at low and high growth temperatures, respectively. We illustrate these key interactions and identify molecular geometries and potential energies by density functional theory calculations. PMID:27314844

  14. 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

  15. Molecular Contamination Investigation Facility (MCIF) Capabilities

    NASA Technical Reports Server (NTRS)

    Soules, David M.

    2013-01-01

    This facility was used to guide the development of ASTM E 1559 center dot Multiple Quartz Crystal Microbalances (QCMs), large sample and spectral effects capability center dot Several instrumented, high vacuum chamber systems are used to evaluate the molecular outgassing characteristics of materials, flight components and other sensitive surfaces. Test materials for spacecraft/instrument selection center.Test flight components for acceptable molecular outgas levels center dot Determine time/temperature vacuum bake-out requirements center. Data used to set limits for use of materials and specific components center. Provide Input Data to Contamination Transport Models -Applied to numerous flight projects over the past 20 years.

  16. 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

  17. 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

  18. Differential molecular interactions between the crystalline and the amorphous phases of celecoxib.

    PubMed

    Gupta, Piyush; Thilagavathi, R; Chakraborti, Asit K; Bansal, Arvind K

    2005-10-01

    We have investigated the differences in molecular interactions between the crystalline (ordered) and amorphous (disordered) phase of a poorly soluble drug, celecoxib. Molecular interactions in the crystalline phase were investigated with the help of Mercury software, using single crystal X-ray diffractometric data for celecoxib. A simulated annealing molecular dynamics approach was used for the assessment of altered molecular interactions in the amorphous phase. Crystalline celecoxib was found to contain an ordered network of H-bonding between all its electron donors (-S=O group, 2-N of pyrazole ring and -C-F) and the acceptor (-N-H). Amorphous celecoxib retained all these interactions in its disordered molecular arrangement, with a relatively stronger H-bonding between the interacting groups, as compared with crystalline celecoxib. However, these inter-molecular interactions differed in strength in the two solid-state forms. The altered configurations of the molecular arrangement in the two phases were supported by the shifts observed in the Fourier-transform infra-red vibrational spectra of respective states. These interactions could have strong implications on devitrification kinetics of amorphous celecoxib, and could further guide the choice of stabilizers for the amorphous form. PMID:16259755

  19. 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

  20. Complex molecular assemblies at hand via interactive simulations.

    PubMed

    Delalande, Olivier; Férey, Nicolas; Grasseau, Gilles; Baaden, Marc

    2009-11-30

    Studying complex molecular assemblies interactively is becoming an increasingly appealing approach to molecular modeling. Here we focus on interactive molecular dynamics (IMD) as a textbook example for interactive simulation methods. Such simulations can be useful in exploring and generating hypotheses about the structural and mechanical aspects of biomolecular interactions. For the first time, we carry out low-resolution coarse-grain IMD simulations. Such simplified modeling methods currently appear to be more suitable for interactive experiments and represent a well-balanced compromise between an important gain in computational speed versus a moderate loss in modeling accuracy compared to higher resolution all-atom simulations. This is particularly useful for initial exploration and hypothesis development for rare molecular interaction events. We evaluate which applications are currently feasible using molecular assemblies from 1900 to over 300,000 particles. Three biochemical systems are discussed: the guanylate kinase (GK) enzyme, the outer membrane protease T and the soluble N-ethylmaleimide-sensitive factor attachment protein receptors complex involved in membrane fusion. We induce large conformational changes, carry out interactive docking experiments, probe lipid-protein interactions and are able to sense the mechanical properties of a molecular model. Furthermore, such interactive simulations facilitate exploration of modeling parameters for method improvement. For the purpose of these simulations, we have developed a freely available software library called MDDriver. It uses the IMD protocol from NAMD and facilitates the implementation and application of interactive simulations. With MDDriver it becomes very easy to render any particle-based molecular simulation engine interactive. Here we use its implementation in the Gromacs software as an example. PMID:19353597

  1. 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.

  2. Molecular dynamics simulation of complex plasmas: interaction of nonlinear waves

    NASA Astrophysics Data System (ADS)

    Durniak, Celine; Samsonov, Dmitry

    2008-11-01

    Complex plasmas consist of micron sized microspheres immersed into ordinary ion-electron plasmas. They exist in solid, liquid, gaseous states and exhibit a range of dynamic phenomena such as waves, solitons, phase transitions, heat transfer. These phenomena can be modelled in complex plasmas at the microscopic or ``molecular'' scale, which is almost impossible in ordinary solids and liquids. We simulate a monolayer complex plasma consisting of 3000 negatively-charged particles (or grains) with the help of molecular dynamics computer simulations. The equations of grain motion are solved using a 5^th order Runge Kutta method taking into account interaction of every grain with each other via a Yukawa potential. The grains are confined more strongly in the vertical direction than in the horizontal. After seeding the grains randomly the code is run until the equilibrium is reached as the grain kinetics energy reduces due to damping force equal to the neutral friction in the experiments and a monolayer crystal lattice is formed. Then we investigate interactions between nonlinear waves in a monolayer strongly coupled complex plasma moving in three dimensions. Different excitations are applied during a short time symmetrically on both sides of the lattice. Structural properties and nonlinear waves characteristics are examined as the pulses propagate across the complex plasma in opposite directions.

  3. 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.

  4. 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.

  5. 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

  6. Study of molecular interactions with 13C DNP-NMR

    NASA Astrophysics Data System (ADS)

    Lerche, Mathilde H.; Meier, Sebastian; Jensen, Pernille R.; Baumann, Herbert; Petersen, Bent O.; Karlsson, Magnus; Duus, Jens Ø.; Ardenkjær-Larsen, Jan H.

    2010-03-01

    NMR spectroscopy is an established, versatile technique for the detection of molecular interactions, even when these interactions are weak. Signal enhancement by several orders of magnitude through dynamic nuclear polarization alleviates several practical limitations of NMR-based interaction studies. This enhanced non-equilibrium polarization contributes sensitivity for the detection of molecular interactions in a single NMR transient. We show that direct 13C NMR ligand binding studies at natural isotopic abundance of 13C gets feasible in this way. Resultant screens are easy to interpret and can be performed at 13C concentrations below μM. In addition to such ligand-detected studies of molecular interaction, ligand binding can be assessed and quantified with enzymatic assays that employ hyperpolarized substrates at varying enzyme inhibitor concentrations. The physical labeling of nuclear spins by hyperpolarization thus provides the opportunity to devise fast novel in vitro experiments with low material requirement and without the need for synthetic modifications of target or ligands.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Mechanically Induced Trapping of Molecular Interactions and Its Applications.

    PubMed

    Garcia-Cordero, Jose L; Maerkl, Sebastian J

    2016-06-01

    Measuring binding affinities and association/dissociation rates of molecular interactions is important for a quantitative understanding of cellular mechanisms. Many low-throughput methods have been developed throughout the years to obtain these parameters. Acquiring data with higher accuracy and throughput is, however, necessary to characterize complex biological networks. Here, we provide an overview of a high-throughput microfluidic method based on mechanically induced trapping of molecular interactions (MITOMI). MITOMI can be used to obtain affinity constants and kinetic rates of hundreds of protein-ligand interactions in parallel. It has been used in dozens of studies to measure binding affinities of transcription factors, map protein interaction networks, identify pharmacological inhibitors, and perform high-throughput, low-cost molecular diagnostics. This article covers the technological aspects of MITOMI and its applications. PMID:25805850

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. New Insights into Molecular Ehrlichia chaffeensis-Host Interactions

    PubMed Central

    Wakeel, Abdul; Zhu, Bing; Yu, Xue-jie; McBride, Jere W.

    2010-01-01

    Ehrlichia chaffeensis is an obligately intracellular bacterium that exhibits tropism for mononuclear phagocytes and survives by reprogramming the host cell. Here we review new information regarding the newly characterized effector molecules and the complex network of molecular host-pathogen interactions that the organism exploits enabling it to thrive and persist intracellularly. PMID:20116446

  4. An Investigation of Technological Innovation: Interactive Television.

    ERIC Educational Resources Information Center

    Robinson, Rhonda S.

    A 5-year case study was implemented to evaluate the two-way Carroll Instructional Television Consortium, which utilizes a cable television network serving four school districts in Illinois. This network permits simultaneous video and audio interactive communication among four high schools. The naturalistic inquiry method employed included…

  5. 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

  6. 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.

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

    PubMed

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

    2015-11-01

    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. PMID:26067937

  8. 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.

  9. 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 ...

  10. 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.

  11. Detection of Binding Site Molecular Interaction Field Similarities.

    PubMed

    Chartier, Matthieu; Najmanovich, Rafael

    2015-08-24

    Protein binding-site similarity detection methods can be used to predict protein function and understand molecular recognition, as a tool in drug design for drug repurposing and polypharmacology, and for the prediction of the molecular determinants of drug toxicity. Here, we present IsoMIF, a method able to identify binding site molecular interaction field similarities across protein families. IsoMIF utilizes six chemical probes and the detection of subgraph isomorphisms to identify geometrically and chemically equivalent sections of protein cavity pairs. The method is validated using six distinct data sets, four of those previously used in the validation of other methods. The mean area under the receiver operator curve (AUC) obtained across data sets for IsoMIF is higher than those of other methods. Furthermore, while IsoMIF obtains consistently high AUC values across data sets, other methods perform more erratically across data sets. IsoMIF can be used to predict function from structure, to detect potential cross-reactivity or polypharmacology targets, and to help suggest bioisosteric replacements to known binding molecules. Given that IsoMIF detects spatial patterns of molecular interaction field similarities, its predictions are directly related to pharmacophores and may be readily translated into modeling decisions in structure-based drug design. IsoMIF may in principle detect similar binding sites with distinct amino acid arrangements that lead to equivalent interactions within the cavity. The source code to calculate and visualize MIFs and MIF similarities are freely available. PMID:26158641

  12. 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.

  13. Challenges in calculating molecular systems with Coulomb interactions

    NASA Astrophysics Data System (ADS)

    Kirnosov, Nikita; Sharkey, Keeper; Adamowicz, Ludwik

    2014-03-01

    The highly accurate quantum mechanical calculations are not only crucial for high-resolution experimental data verification, but may also serve as a guide in the field of exotic systems exploration. Including all non-relativistic effects in a single-step variational approach and rigorously separating out the center of mass motion allows us to build a reliable model for calculating bound states of molecular systems with Coulomb interactions. In these calculations the wave function of the system is expanded in terms of explicitly correlated Gaussian (ECG) basis functions. Examples of calculations of energies and other properties of some molecular systems will be presented.

  14. STM investigation of pyridine interaction with heteropoly acid monolayers

    SciTech Connect

    Song, I.K.; Kaba, M.S.; Barteau, M.A.

    1996-10-31

    In this paper, scanning tunneling microscopy (STM) images and tunneling spectra of H{sub 3}PMo{sub 12}O{sub 40} and Cs{sub 3}PMo{sub 12}O{sub 40} deposited on graphite surfaces were obtained in air before and after pyridine adsorption on arrays of these heteropoly HPAs, and the interactions with pyridine were probed at the molecular level using STM. The interactions were subsequently confirmed by infrared spectroscopy. These studies demonstrate the selective interaction of pyridine with acid sites in these arrays and the dramatic alteration of array structure which results from this interaction. 46 refs., 8 figs.

  15. Collective transport of weakly interacting molecular motors with Langmuir kinetics

    NASA Astrophysics Data System (ADS)

    Chandel, Sameep; Chaudhuri, Abhishek; Muhuri, Sudipto

    2015-04-01

    Filament-based intracellular transport involves the collective action of molecular motor proteins. Experimental evidences suggest that microtubule (MT) filament bound motor proteins such as kinesins weakly interact among themselves during transport and with the surrounding cellular environment. Motivated by these observations we study a driven lattice gas model for collective unidirectional transport of molecular motors on open filament. This model incorporates short-range next-nearest-neighbour (NNN) interactions between the motors and couples the transport process on filament with surrounding cellular environment through adsorption-desorption Langmuir kinetics (LK) of the motors. We analyse this model within the framework of a mean-field (MF) theory in the limit of weak interactions between the motors. We point to the mapping of this model with the non-conserved version of the Katz-Lebowitz-Spohn (KLS) model. The system exhibits rich phase behavior with a variety of inhomogeneous phases including localized shocks in the bulk of the filament. We obtain the steady-state density and current profiles, analyse their variation as a function of the strength of interaction and construct the non-equilibrium MF phase diagram. We compare these MF results with Monte Carlo simulations and find that the MF analysis shows reasonably good agreement with simulation results as long as the motors are weakly interacting. For sufficently strong NNN interaction between the motors, the mean-field results deviate significantly, and for very strong NNN interaction in the absence of LK, the current in the lattice is determined solely by the NNN interaction parameter and it becomes independent of entry and exit rates of motors at the filament boundaries.

  16. WebInterViewer: visualizing and analyzing molecular interaction networks

    PubMed Central

    Han, Kyungsook; Ju, Byong-Hyon; Jung, Haemoon

    2004-01-01

    Molecular interaction networks, such as those involving protein–protein and protein–DNA interactions, often consist of thousands of nodes or even more, which severely limits the usefulness of many graph drawing tools because they become too slow for interactive analysis of the networks and because they produce cluttered drawings with many edge crossings. We present a new, fast-layout algorithm and its implementation called WebInterViewer for visualizing large-scale molecular interaction networks. WebInterViewer (i) finds a layout of the connected components of an entire network, (ii) finds a global layout of nodes with respect to pivot nodes within the connected components and (iii) refines the local layout of each connected component by first relocating midnodes with respect to their cutvertices and the direct neighbors of the cutvertices, and then relocating all nodes with respect to their neighbors within distance 2. The advantages of WebInterViewer over classical graph drawing methods include the facts that (i) it is an order of magnitude faster, (ii) it can visualize data directly from protein interaction databases and (iii) it provides several abstraction and comparison operations for analyzing large-scale biological networks effectively. WebInterViewer is accessible at http://interviewer.inha.ac.kr/. PMID:15215357

  17. 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).

  18. 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

  19. Supernova remnant masers: Shock interactions with molecular clouds

    NASA Astrophysics Data System (ADS)

    Hewitt, John William

    Maser emission from the 1720-MHz transition of hydroxyl(OH) has identified shock interactions in 10% of all supernova remnants(SNRs). Such maser-emitting SNRs are also bright in molecular line emission. Though somewhat rare, SNRs interacting with dense molecular clouds are an important class in which to study cosmic ray acceleration, SNR evolution, and effects on the energetics and chemistry of the interstellar medium. To study molecular shocks via a multiwavelength approach, the VLA, GBT, Spitzer Space Telescope have been used in the following ways: (i) With the GBT widespread OH(1720 MHz) emission and absorption in other OH lines is observed across the interaction site. Observations of all four ground-state transitions at 1720, 1667/5 and 1612 MHz allows us to model OH excitation, yielding the temperature, density and OH abundance in the post-shock gas. Maser emission is found to have a higher flux density with the GBT than with high-resolution VLA observations for 10 of 15 observed remnants, suggesting maser emission is present on large spatial scales. (ii) Sensitive VLA observations of select SNRs (W44, IC 443, Kes 69, 3C 391, G357.7+0.3) reveal the nature of enhanced 1720 MHz emission. Numerous weak compact masers as well as diffuse extended emission are detected tracing the shock-front. Zeeman splitting of masers permits the post-shock magnetic field strength and the line of sight field direction to be directly measured. (iii) Rotational lines of molecular hydrogen are detected at the position of several masers with Spitzer IRS spectroscopy between 5 and 35 mm. Excitation of the hydrogen lines requires the passage of a C-type shock through dense molecular gas, in agreement with the conditions derived from OH excitation. The presence of bright ionic lines requires multiple shocks present at the interaction site. (iv) A new survey for SNR-masers has identified four new interacting SNRs within 10 degrees of the Galactic Center. Maser-emitting SNRs are found to

  20. 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.

  1. 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}.

  2. Molecular pharmacology of the interaction of anthracyclines with iron.

    PubMed

    Xu, X; Persson, H L; Richardson, D R

    2005-08-01

    Although anthracyclines such as doxorubicin are widely used antitumor agents, a major limitation for their use is the development of cardiomyopathy at high cumulative doses. This severe adverse side effect may be due to interactions with cellular iron metabolism, because iron loading promotes anthracycline-induced cell damage. On the other hand, anthracycline-induced cardiotoxicity is significantly alleviated by iron chelators (e.g., desferrioxamine and dexrazoxane). The molecular mechanisms by which anthracyclines interfere with cellular iron trafficking are complex and still unclear. Doxorubicin can directly bind iron and can perturb iron metabolism by interacting with multiple molecular targets, including the iron regulatory proteins (IRP) 1 and 2. The RNA-binding activity of these molecules regulates synthesis of the transferrin receptor 1 and ferritin, which are crucial proteins involved in iron uptake and storage, respectively. At present, it is not clear whether doxorubicin affects IRP1-RNA-binding activity by intracellular formation of doxorubicinol and/or by generation of the doxorubicin-iron(III) complex. Furthermore, doxorubicin prevents the mobilization of iron from ferritin by a mechanism that may involve lysosomal degradation of this protein. Prevention of iron mobilization from ferritin would probably disturb vital cellular functions as a result of inhibition of essential iron-dependent proteins, such as ribonucleotide reductase. This review discusses the molecular interactions of anthracyclines with iron metabolism and the development of cardioprotective strategies such as iron chelators. PMID:15883202

  3. Human Lactate Dehydrogenase A Inhibitors: A Molecular Dynamics Investigation

    PubMed Central

    Shi, Yun; Pinto, B. Mario

    2014-01-01

    Lactate dehydrogenase A (LDHA) is an important enzyme in fermentative glycolysis, generating most energy for cancer cells that rely on anaerobic respiration even under normal oxygen concentrations. This renders LDHA a promising molecular target for the treatment of various cancers. Several efforts have been made recently to develop LDHA inhibitors with nanomolar inhibition and cellular activity, some of which have been studied in complex with the enzyme by X-ray crystallography. In this work, we present a molecular dynamics (MD) study of the binding interactions of selected ligands with human LDHA. Conventional MD simulations demonstrate different binding dynamics of inhibitors with similar binding affinities, whereas steered MD simulations yield discrimination of selected LDHA inhibitors with qualitative correlation between the in silico unbinding difficulty and the experimental binding strength. Further, our results have been used to clarify ambiguities in the binding modes of two well-known LDHA inhibitors. PMID:24466056

  4. 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

  5. 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

  6. Molecular interactions of pesticides at the soil-water interface.

    PubMed

    Shirzadi, Azadeh; Simpson, Myrna J; Kumar, Rajeev; Baer, Andrew J; Xu, Yunping; Simpson, André J

    2008-08-01

    High-resolution magic angle spinning (HR-MAS) NMR spectroscopy combined with saturation-transfer double difference (STDD) NMR can be used to analyze the molecular-level interactions of pesticides and whole soils occurring at the soil-water interface. Here 1H HR-MAS STDD NMR has been applied to some common pesticides (trifluralin, acifluorfen, and (4-nitro-3-(trifluoromethyl) phenol) and a pesticide degradation product (1-naphthol). Results indicate that dipolar interactions, H-bonding, hydrophobic associations, and potentially pi-pi interactions are the predominant sorption mechanisms for these molecules at the soil-aqueous interface. It is evident that the physical and chemical characteristics of soil are highly influential in determining the mechanisms of pesticide sorption, as they significantly affect soil conformation. In particular, different binding mechanisms were observed for 1-naphthol in soil swollen using a buffer versus D2O, indicating that the K(oc) alone may not be enough to accurately predict the behavior of a molecule in a real soil environment. Preliminary kinetic-based studies suggest that both the swelling solvent and soil moisture content significantly influence the sequestration of trifluralin. These studies demonstrate that HR-MAS and STDD NMR are powerful and versatile tools which can be applied to expand our knowledge of the mechanistic interactions of agrochemicals at the molecular level. PMID:18754469

  7. Hunting complex differential gene interaction patterns across molecular contexts

    PubMed Central

    Song, Mingzhou; Zhang, Yang; Katzaroff, Alexia J.; Edgar, Bruce A.; Buttitta, Laura

    2014-01-01

    Heterogeneity in genetic networks across different signaling molecular contexts can suggest molecular regulatory mechanisms. Here we describe a comparative chi-square analysis (CPχ2) method, considerably more flexible and effective than other alternatives, to screen large gene expression data sets for conserved and differential interactions. CPχ2 decomposes interactions across conditions to assess homogeneity and heterogeneity. Theoretically, we prove an asymptotic chi-square null distribution for the interaction heterogeneity statistic. Empirically, on synthetic yeast cell cycle data, CPχ2 achieved much higher statistical power in detecting differential networks than alternative approaches. We applied CPχ2 to Drosophila melanogaster wing gene expression arrays collected under normal conditions, and conditions with overexpressed E2F and Cabut, two transcription factor complexes that promote ectopic cell cycling. The resulting differential networks suggest a mechanism by which E2F and Cabut regulate distinct gene interactions, while still sharing a small core network. Thus, CPχ2 is sensitive in detecting network rewiring, useful in comparing related biological systems. PMID:24482443

  8. 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

  9. 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

  10. Flexibility and enzymatic cold-adaptation: a comparative molecular dynamics investigation of the elastase family.

    PubMed

    Papaleo, Elena; Riccardi, Laura; Villa, Chiara; Fantucci, Piercarlo; De Gioia, Luca

    2006-08-01

    Molecular dynamics simulations of representative mesophilic and psycrophilic elastases have been carried out at different temperatures to explore the molecular basis of cold adaptation inside a specific enzymatic family. The molecular dynamics trajectories have been compared and analyzed in terms of secondary structure, molecular flexibility, intramolecular and protein-solvent interactions, unravelling molecular features relevant to rationalize the efficient catalytic activity of psychrophilic elastases at low temperature. The comparative molecular dynamics investigation reveals that modulation of the number of protein-solvent interactions is not the evolutionary strategy followed by the psycrophilic elastase to enhance catalytic activity at low temperature. In addition, flexibility and solvent accessibility of the residues forming the catalytic triad and the specificity pocket are comparable in the cold- and warm-adapted enzymes. Instead, loop regions with different amino acid composition in the two enzymes, and clustered around the active site or the specificity pocket, are characterized by enhanced flexibility in the cold-adapted enzyme. Remarkably, the psycrophilic elastase is characterized by reduced flexibility, when compared to the mesophilic counterpart, in some scattered regions distant from the functional sites, in agreement with hypothesis suggesting that local rigidity in regions far from functional sites can be beneficial for the catalytic activity of psychrophilic enzymes. PMID:16920043

  11. 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.

  12. Quantitative analysis of genomic element interactions by molecular colony technique

    PubMed Central

    Gavrilov, Alexey A.; Chetverina, Helena V.; Chermnykh, Elina S.; Razin, Sergey V.; Chetverin, Alexander B.

    2014-01-01

    Distant genomic elements were found to interact within the folded eukaryotic genome. However, the used experimental approach (chromosome conformation capture, 3C) enables neither determination of the percentage of cells in which the interactions occur nor demonstration of simultaneous interaction of >2 genomic elements. Each of the above can be done using in-gel replication of interacting DNA segments, the technique reported here. Chromatin fragments released from formaldehyde–cross-linked cells by sodium dodecyl sulfate extraction and sonication are distributed in a polyacrylamide gel layer followed by amplification of selected test regions directly in the gel by multiplex polymerase chain reaction. The fragments that have been cross-linked and separate fragments give rise to multi- and monocomponent molecular colonies, respectively, which can be distinguished and counted. Using in-gel replication of interacting DNA segments, we demonstrate that in the material from mouse erythroid cells, the majority of fragments containing the promoters of active β-globin genes and their remote enhancers do not form complexes stable enough to survive sodium dodecyl sulfate extraction and sonication. This indicates that either these elements do not interact directly in the majority of cells at a given time moment, or the formed DNA–protein complex cannot be stabilized by formaldehyde cross-linking. PMID:24369423

  13. FTIR investigation of non-volatile molecular nanoparticles

    NASA Astrophysics Data System (ADS)

    Signorell, R.; Kunzmann, M. K.; Suhm, M. A.

    2000-10-01

    A new approach for the spectroscopic investigation of non-volatile molecular nanoparticles with diameters in the range between 10 and 100 nm is proposed. The nanoparticles are produced in an electrospray with subsequent solvent evaporation. The number size distribution of the generated aerosol is determined with a scanning mobility particle sizer. Fourier transform infrared spectroscopy is used to study the vibrational dynamics of the nanoparticles. As an example, we have investigated sucrose nanoparticles with six different diameters between 36 and 82 nm. From a comparison with different bulk phase spectra, we conclude that sucrose aerosols are formed in a solid amorphous state.

  14. 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

  15. Ab initio investigation of benzene clusters: Molecular tailoring approach

    NASA Astrophysics Data System (ADS)

    Mahadevi, A. Subha; Rahalkar, Anuja P.; Gadre, Shridhar R.; Sastry, G. Narahari

    2010-10-01

    An exhaustive study on the clusters of benzene (Bz)n, n =2-8, at MP2/6-31++G∗∗ level of theory is reported. The relative strengths of CH-π and π-π interactions in these aggregates are examined, which eventually govern the pattern of cluster formation. A linear scaling method, viz., molecular tailoring approach (MTA), is efficiently employed for studying the energetics and growth patterns of benzene clusters consisting up to eight benzene (Bz) units. Accuracy of MTA-based calculations is appraised by performing the corresponding standard calculations wherever possible, i.e., up to tetramers. For benzene tetramers, the error introduced in energy is of the order of 0.1 mH (˜0.06 kcal/mol). Although for higher clusters the error may build up, further corrections based on many-body interaction energy analysis substantially reduce the error in the MTA-estimate. This is demonstrated for a prototypical case of benzene hexamer. A systematic way of building up a cluster of n monomers (n-mer) which employs molecular electrostatic potential of an (n -1)-mer is illustrated. The trends obtained using MTA method are essentially identical to those of the standard methods in terms of structure and energy. In summary, this study clearly brings out the possibility of effecting such large calculations, which are not possible conventionally, by the use of MTA without a significant loss of accuracy.

  16. Comprehensive Characterization of Molecular Interactions Based on Nanomechanics

    PubMed Central

    Lang, Hans-Peter; Gerber, Christoph; Hegner, Martin

    2008-01-01

    Molecular interaction is a key concept in our understanding of the biological mechanisms of life. Two physical properties change when one molecular partner binds to another. Firstly, the masses combine and secondly, the structure of at least one binding partner is altered, mechanically transducing the binding into subsequent biological reactions. Here we present a nanomechanical micro-array technique for bio-medical research, which not only monitors the binding of effector molecules to their target but also the subsequent effect on a biological system in vitro. This label-free and real-time method directly and simultaneously tracks mass and nanomechanical changes at the sensor interface using micro-cantilever technology. To prove the concept we measured lipid vesicle (∼748*106 Da) adsorption on the sensor interface followed by subsequent binding of the bee venom peptide melittin (2840 Da) to the vesicles. The results show the high dynamic range of the instrument and that measuring the mass and structural changes simultaneously allow a comprehensive discussion of molecular interactions. PMID:18978938

  17. 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.

  18. 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

  19. A general, accurate procedure for calculating molecular interaction force.

    PubMed

    Yang, Pinghai; Qian, Xiaoping

    2009-09-15

    The determination of molecular interaction forces, e.g., van der Waals force, between macroscopic bodies is of fundamental importance for understanding sintering, adhesion and fracture processes. In this paper, we develop an accurate, general procedure for van der Waals force calculation. This approach extends a surface formulation that converts a six-dimensional (6D) volume integral into a 4D surface integral for the force calculation. It uses non-uniform rational B-spline (NURBS) surfaces to represent object surfaces. Surface integrals are then done on the parametric domain of the NURBS surfaces. It has combined advantages of NURBS surface representation and surface formulation, including (1) molecular interactions between arbitrary-shaped objects can be represented and evaluated by the NURBS model further common geometries such as spheres, cones, planes can be represented exactly and interaction forces are thus calculated accurately; (2) calculation efficiency is improved by converting the volume integral to the surface integral. This approach is implemented and validated via its comparison with analytical solutions for simple geometries. Calculation of van der Waals force between complex geometries with surface roughness is also demonstrated. A tutorial on the NURBS approach is given in Appendix A. PMID:19596335

  20. [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

  1. 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.

  2. 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

  3. [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

  4. 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.

  5. 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

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

    PubMed Central

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

    2015-01-01

    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. PMID:26140374

  7. Molecular nutrition: Interaction of nutrients, gene regulations and performances.

    PubMed

    Sato, Kan

    2016-07-01

    Nutrition deals with ingestion of foods, digestion, absorption, transport of nutrients, intermediary metabolism, underlying anabolism and catabolism, and excretion of unabsorbed nutrients and metabolites. In addition, nutrition interacts with gene expressions, which are involved in the regulation of animal performances. Our laboratory is concerned with the improvement of animal productions, such as milks, meats and eggs, with molecular nutritional aspects. The present review shows overviews on the nutritional regulation of metabolism, physiological functions and gene expressions to improve animal production in chickens and dairy cows. PMID:27110862

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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

  14. A molecular dynamics study on slow ion interactions with the polycyclic aromatic hydrocarbon molecule anthracene

    SciTech Connect

    Postma, J.; Hoekstra, R.; Schlathölter, T.; Tielens, A. G. G. M.

    2014-03-01

    Atomic collisions with polycyclic aromatic hydrocarbon (PAH) molecules are astrophysically particularly relevant for collision energies of less than 1 keV. In this regime, the interaction dynamics are dominated by elastic interactions. We have employed a molecular dynamics simulation based on analytical interaction potentials to model the interaction of low energy hydrogen and helium projectiles with isolated anthracene (C{sub 14}H{sub 10}) molecules. This approach allows for a very detailed investigation of the elastic interaction dynamics on an event by event basis. From the simulation data the threshold projectile kinetic energies above which direct C atom knock out sets in were determined. Anthracene differential energy transfer cross sections and total (dissociation) cross sections were computed for a wide range of projectile kinetic energies. The obtained results are interpreted in the context of PAH destruction in astrophysical environments.

  15. Interactions between halide anions and a molecular hydrophobic interface.

    PubMed

    Rankin, Blake M; Hands, Michael D; Wilcox, David S; Fega, K Rebecca; Slipchenko, Lyudmila V; Ben-Amotz, Dor

    2013-01-01

    Interactions between halide ions (fluoride and iodide) and t-butyl alcohol (TBA) dissolved in water are probed using a recently developed hydration-shell spectroscopic technique and theoretical cluster and liquid calculations. High ignal-to-noise Raman spectroscopic measurements are combined with multivariate curve resolution (Raman-MCR) to reveal that while there is little interaction between aqueous fluoride ions and TBA, iodide ions break down the tetrahedral hydration-shell structure of TBA and produce a red-shift in its CH stretch frequency, in good agreement with the theoretical effective fragment potential (EFP) molecular dynamics simulations and hybrid quantum/EFP frequency calculations. The results imply that there is a significantly larger probability of finding iodide than fluoride in the first hydration shell of TBA, although the local iodide concentration is apparently not as high as in the surrounding bulk aqueous NaI solution. PMID:23795504

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

    PubMed Central

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

    2015-01-01

    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. PMID:26580609

  17. 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

    2015-01-01

    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. PMID:26580609

  18. 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.

  19. DASMI: exchanging, annotating and assessing molecular interaction data

    PubMed Central

    Blankenburg, Hagen; Finn, Robert D.; Prlić, Andreas; Jenkinson, Andrew M.; Ramírez, Fidel; Emig, Dorothea; Schelhorn, Sven-Eric; Büch, Joachim; Lengauer, Thomas; Albrecht, Mario

    2009-01-01

    Motivation: Ever increasing amounts of biological interaction data are being accumulated worldwide, but they are currently not readily accessible to the biologist at a single site. New techniques are required for retrieving, sharing and presenting data spread over the Internet. Results: We introduce the DASMI system for the dynamic exchange, annotation and assessment of molecular interaction data. DASMI is based on the widely used Distributed Annotation System (DAS) and consists of a data exchange specification, web servers for providing the interaction data and clients for data integration and visualization. The decentralized architecture of DASMI affords the online retrieval of the most recent data from distributed sources and databases. DASMI can also be extended easily by adding new data sources and clients. We describe all DASMI components and demonstrate their use for protein and domain interactions. Availability: The DASMI tools are available at http://www.dasmi.de/ and http://ipfam.sanger.ac.uk/graph. The DAS registry and the DAS 1.53E specification is found at http://www.dasregistry.org/. Contact: mario.albrecht@mpi-inf.mpg.de Supplementary information: Supplementary data and all figures in color are available at Bioinformatics online. PMID:19420069

  20. 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

  1. 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

  2. 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

  3. Theoretical investigation on the glycan-binding specificity of Agrocybe cylindracea galectin using molecular modeling and molecular dynamics simulation studies.

    PubMed

    Parasuraman, Ponnusamy; Murugan, Veeramani; Selvin, Jeyasigamani F A; Gromiha, M Michael; Fukui, Kazuhiko; Veluraja, Kasinadar

    2015-09-01

    Galectins are β-galactoside binding proteins which have the ability to serve as potent antitumor, cancer biomarker, and induce tumor cell apoptosis. Agrocybe cylindracea galectin (ACG) is a fungal galectin which specifically recognizes α(2,3)-linked sialyllactose at the cell surface that plays extensive roles in the biological recognition processes. To investigate the change in glycan-binding specificity upon mutations, single point and double point site-directed in silico mutations are performed at the binding pocket of ACG. Molecular dynamics (MD) simulation studies are carried out for the wild-type (ACG) and single point (ACG1) and double point (ACG2) mutated ACGs to investigate the dynamics of substituted mutants and their interactions with the receptor sialyllactose. Plausible binding modes are proposed for galectin-sialylglycan complexes based on the analysis of hydrogen bonding interactions, total pair-wise interaction energy between the interacting binding site residues and sialyllactose and binding free energy of the complexes using molecular mechanics-Poisson-Boltzmann surface area. Our result shows that high contribution to the binding in different modes is due to the direct and water-mediated hydrogen bonds. The binding specificity of double point mutant Y59R/N140Q of ACG2 is found to be high, and it has 26 direct and water-mediated hydrogen bonds with a relatively low-binding free energy of -47.52 ± 5.2 kcal/mol. We also observe that the substituted mutant Arg59 is crucial for glycan-binding and for the preference of α(2,3)-linked sialyllactose at the binding pocket of ACG2 galectin. When compared with the wild-type and single point mutant, the double point mutant exhibits enhanced affinity towards α(2,3)-linked sialyllactose, which can be effectively used as a model for biological cell marker in cancer therapeutics. PMID:25760468

  4. Isothermal microcalorimetry to investigate non specific interactions in biophysical chemistry.

    PubMed

    Ball, Vincent; Maechling, Clarisse

    2009-10-01

    Isothermal titration microcalorimetry (ITC) is mostly used to investigate the thermodynamics of "specific" host-guest interactions in biology as well as in supramolecular chemistry. The aim of this review is to demonstrate that ITC can also provide useful information about non-specific interactions, like electrostatic or hydrophobic interactions. More attention will be given in the use of ITC to investigate polyelectrolyte-polyelectrolyte (in particular DNA-polycation), polyelectrolyte-protein as well as protein-lipid interactions. We will emphasize that in most cases these "non specific" interactions, as their definition will indicate, are favoured or even driven by an increase in the entropy of the system. The origin of this entropy increase will be discussed for some particular systems. We will also show that in many cases entropy-enthalpy compensation phenomena occur. PMID:20111693

  5. Isothermal Microcalorimetry to Investigate Non Specific Interactions in Biophysical Chemistry

    PubMed Central

    Ball, Vincent; Maechling, Clarisse

    2009-01-01

    Isothermal titration microcalorimetry (ITC) is mostly used to investigate the thermodynamics of “specific” host-guest interactions in biology as well as in supramolecular chemistry. The aim of this review is to demonstrate that ITC can also provide useful information about non-specific interactions, like electrostatic or hydrophobic interactions. More attention will be given in the use of ITC to investigate polyelectrolyte-polyelectrolyte (in particular DNA-polycation), polyelectrolyte-protein as well as protein-lipid interactions. We will emphasize that in most cases these “non specific” interactions, as their definition will indicate, are favoured or even driven by an increase in the entropy of the system. The origin of this entropy increase will be discussed for some particular systems. We will also show that in many cases entropy-enthalpy compensation phenomena occur. PMID:20111693

  6. 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.

  7. 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. PMID:24226412

  8. 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

  9. Investigation of radiative interactions in chemically reacting supersonic internal flows

    NASA Technical Reports Server (NTRS)

    Tiwari, S. N.; Chandrasekhar, R.; Thomas, A. M.; Drummond, J. P.

    1991-01-01

    Analyses and numerical procedures are presented to investigate the radiative interactions of absorbing-emitting species in chemically reacting supersonic flow in various ducts. Specific attention is directed in investigating the radiative contributions of H2O, OH, and NO under realistic physical and flow conditions. The radiative interactions in reacting flows are investigated by considering the supersonic flow of premixed hydrogen and air in a channel with a compression corner at the lower boundary. The results indicate that radiation can have significant influence on the flowfield and species production depending on the chemistry model employed.

  10. Molecular View of Protein Crystal Growth: Molecular Interactions, Surface Reconstruction and Growth Mechanism

    NASA Technical Reports Server (NTRS)

    Nadarajah, Arunan; Li, Huayu; Konnert, John H.; Pusey, Marc L.

    2000-01-01

    Studies of the growth and molecular packing of tetragonal lysozyme crystals suggest that there is an underlying molecular growth mechanism, in addition to the classical one involving screw dislocation/2D) nucleation growth. These crystals are constructed by strongly bonded molecular chains forming helices about the 43 axes. The helices are connected to each other by weaker bonds. Crystal growth proceeds by the formation of these 4(sub 3) helices, which would explain some unexpected observations by earlier investigators, such as bimolecular growth steps on the (110) face. Another consequence of these molecular considerations is that only one of two possible packing arrangements could occur on the crystal faces and that their growth unit was at least a tetramer corresponding to the 4(sub 3) helix. Two new high resolution atomic force microscopy (AFM) techniques were developed to directly confirm these predictions on tetragonal lysozyme crystals. Most earlier investigations of protein crystal growth with AFM were in the low resolution mode which is adequate to investigate the classical growth mechanisms, but cannot resolve molecular features and mechanisms. Employing the first of the newly developed techniques, high resolution AFM images of the (110) face were compared with the theoretically constructed images for the two possible packing arrangements on this face. The prediction that the molecular packing arrangement of these faces corresponded to that for complete 4(sub 3) helices was confirmed in this manner. This investigation also showed the occurrence of surface reconstruction on protein crystals. The molecules on the surface of the (110) face were found to pack closer along the 4(sub 3) axes than those in the interior. The second new AFM technique was used to follow the growth process by measuring the dimensions of individual growth units on the (110) face. Linescans across a growth step, performed near the saturation limit of the crystals, allowed the growth

  11. 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

  12. 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.

  13. Experimental investigations of thermal interaction between corium and coolants

    NASA Astrophysics Data System (ADS)

    Zagorul'ko, Yu. I.; Zhmurin, V. G.; Volov, A. N.; Kovalev, Yu. P.

    2008-03-01

    We present a generalized analysis of the experimental results from investigations of thermal interaction in corium simulators (melts of thermite mixtures U + Mo3 and Zr + Fe2O3)-coolant (Na and H2O) systems. We also present the results from experimental assessments of the kinematic characteristics pertinent to the displacement of materials during the thermal interaction process and the coefficients for conversion of the corium thermal energy into mechanical work.

  14. 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

  15. 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.

  16. Gap distance and interactions in a molecular tunnel junction.

    PubMed

    Chang, Shuai; He, Jin; Zhang, Peiming; Gyarfas, Brett; Lindsay, Stuart

    2011-09-14

    The distance between electrodes in a tunnel junction cannot be determined from the external movement applied to the electrodes because of interfacial forces that distort the electrode geometry at the nanoscale. These distortions become particularly complex when molecules are present in the junction, as demonstrated here by measurements of the AC response of a molecular junction over a range of conductivities from microsiemens to picosiemens. Specific chemical interactions within the junction lead to distinct features in break-junction data, and these have been used to determine the electrode separation in a junction functionalized with 4(5)-(2-mercaptoethyl)-1H-imidazole-2-carboxamide, a reagent developed for reading DNA sequences. PMID:21838292

  17. 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.

  18. 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

  19. Interaction of Lysozyme with Rhodamine B: A combined analysis of spectroscopic & molecular docking.

    PubMed

    Millan, Sabera; Satish, Lakkoji; Kesh, Sandeep; Chaudhary, Yatendra S; Sahoo, Harekrushna

    2016-09-01

    The interaction of Rhodamine B (RB) with Lysozyme (Lys) was investigated by different optical spectroscopic techniques such as absorption, fluorescence, and circular-dichroism (CD), along with molecular docking studies. The fluorescence results (including steady-state and time-resolved mode) revealed that the addition of RB effectively causes strong quenching of intrinsic fluorescence in Lysozyme and mostly, by the static quenching mechanism. Different binding and thermodynamic parameters were calculated at different temperatures and the binding constant value was found to be 2963.54Lmol(-1) at 25°C. The average distance (r0) was found to be 3.31nm according to Förster's theory of non-radiative energy transfer between Lysozyme and RB. The conformational change in Lysozyme during interaction with RB was confirmed from absorbance, synchronous fluorescence, and circular dichroism measurements. Finally, molecular docking studies were done to confirm that the dye binds with Lysozyme. PMID:27390893

  20. Molecular interaction of 2-mercaptobenzimidazole with catalase reveals a potentially toxic mechanism of the inhibitor.

    PubMed

    Teng, Yue; Zou, Luyi; Huang, Ming; Zong, Wansong

    2014-12-01

    2-Mercaptobenzimidazole (MBI) is widely utilized as a corrosion inhibitor, copper-plating brightener and rubber accelerator. The residue of MBI in the environment possesses a potential risk to human health. In this work, the toxic interaction of MBI with the important antioxidant enzyme catalase (CAT) was investigated using spectroscopic and molecular docking methods under physiological conditions. MBI can spontaneously bind with CAT with one binding site through hydrogen bonds and van der Waals forces to form MBI-CAT complex. The molecular docking study revealed that MBI bound into the CAT interface of chains B and C, which led to some conformational and microenvironmental changes of CAT and further resulted in the inhibition of CAT activity. This present study provides direct evidence at a molecular level to show that exposure to MBI could induce changes in the structure and function of the enzyme CAT. PMID:25463673

  1. 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.

  2. 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.

  3. 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)].

  4. Microparadigms: chains of collective reasoning in publications about molecular interactions.

    PubMed

    Rzhetsky, Andrey; Iossifov, Ivan; Loh, Ji Meng; White, Kevin P

    2006-03-28

    We analyzed a very large set of molecular interactions that had been derived automatically from biological texts. We found that published statements, regardless of their verity, tend to interfere with interpretation of the subsequent experiments and, therefore, can act as scientific "microparadigms," similar to dominant scientific theories [Kuhn, T. S. (1996) The Structure of Scientific Revolutions (Univ. Chicago Press, Chicago)]. Using statistical tools, we measured the strength of the influence of a single published statement on subsequent interpretations. We call these measured values the momentums of the published statements and treat separately the majority and minority of conflicting statements about the same molecular event. Our results indicate that, when building biological models based on published experimental data, we may have to treat the data as highly dependent-ordered sequences of statements (i.e., chains of collective reasoning) rather than unordered and independent experimental observations. Furthermore, our computations indicate that our data set can be interpreted in two very different ways (two "alternative universes"): one is an "optimists' universe" with a very low incidence of false results (<5%), and another is a "pessimists' universe" with an extraordinarily high rate of false results (>90%). Our computations deem highly unlikely any milder intermediate explanation between these two extremes. PMID:16543380

  5. Investigation of Protein-Protein Interactions and Conformational Changes in Hedgehog Signaling Pathway by FRET.

    PubMed

    Fu, Lin; Lv, Xiangdong; Xiong, Yue; Zhao, Yun

    2015-01-01

    Protein-protein interactions and signal-induced protein conformational changes are fundamental molecular events that are considered as essential in modern life sciences. Among various techniques developed to study such phenomena, fluorescence resonance energy transfer (FRET) is a widely used method with many advantages in detecting these molecular events. Here, we describe the application of FRET in the mechanistic investigation of cell signal transduction, taking the example of the Hh signaling pathway, which plays a critical role in embryonic development and tissue homeostasis. A number of general guidelines as well as some key notes have been summarized as a protocol for reader's reference. PMID:26179039

  6. Thermal and molecular investigation of laser tissue welding

    NASA Astrophysics Data System (ADS)

    Small, Ward, IV

    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 on 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 the probability of long-term success. Molecular effects induced in the tissue by laser irradiation were investigated by measuring the concentrations of specific collagen covalent crosslinks and measuring the infrared absorption spectra before and after the laser exposure. This investigation yielded results pertaining to both the methods and mechanisms of laser tissue welding. The combination of two-color infrared thermometry to obtain accurate surface temperatures free from emissivity bias and computer modeling illustrated the importance of including evaporation in the simulations, which effectively serves as an inherent cooling mechanism during laser irradiation. Moreover, the hydration state predicted by the model was useful in assessing the role of electrostatic versus covalent bonding in the fusion. These tools also helped elicit differences between dye- enhanced liquid solders and solid-matrix patches in laser-assisted tissue welding, demonstrating the significance of repeatable energy delivery. Surprisingly, covalent bonds

  7. Molecular mechanism investigation of the neutralization of cadmium toxicity by transferrin.

    PubMed

    Wang, Jing; Wang, Jinhu; Song, Wei; Yang, Xinping; Zong, Wansong; Liu, Rutao

    2016-02-01

    Cadmium adversely affects the biological function of the liver. Transferrin might be involved in the detoxification system of cadmium. However, owing to the lack of investigation of the molecular mechanism of cadmium conjugating to transferrin, the role of transferrin in cadmium detoxification in the liver and how transferrin undergoes conformational and functional changes upon cadmium binding are not clear. In this article, we demonstrated the potential role of transferrin in the protection of the mouse primary hepatocytes against cadmium toxicity. After the incubation of hepatocytes with 10 and 100 μM CdCl2, pretreatment with transferrin significantly attenuated the reduction of cell viability in comparison with the samples treated with CdCl2 alone. Furthermore, a detailed molecular mechanism investigation of the interaction of CdCl2 with transferrin was reported using biophysical methods. Multi-spectroscopic measurements showed that CdCl2 formed complexes with transferrin and caused structural and conformational changes of transferrin. Isothermal titration calorimetry measurements revealed that transferrin has two classes of binding sites with different binding constants for CdCl2 binding. Hydrophobic forces and electrostatic forces are the major driving forces of the interaction. Preferred specific binding sites on transferrin were identified by dialysis experiments, molecular docking studies and molecular dynamics simulations. Upon low CdCl2 concentration exposure, no content of iron was released from transferrin because CdCl2 preferentially binds to the surface of transferrin molecules. Upon higher CdCl2 concentration exposure, the release of iron content from transferrin was observed due to the interaction of CdCl2 with the key residues around iron binding sites. PMID:26750974

  8. A Investigation of a Possible Molecular Effect in Ion Atom Collision Using a Gaseous Argon Target

    NASA Astrophysics Data System (ADS)

    Arora, Sanjeev

    1992-01-01

    The present work deals with an investigation of the molecular effect, which is defined as the difference in experimental results using isotachic atomic ion and molecular ion beams in ion atom collisions. Previous studies have dealt almost exclusively with total cross section measurements. This thesis explores the idea that the molecular effect may be more pronounced in the differential ionization probability of the target atoms. Also, a gaseous argon target of sufficiently low density was used in order to ensure that the two correlated protons in the H _2^{+} beam did not interact with two adjacent target atoms simultaneously. We report that, contrary to the expectations noted above, the molecular effect in the K shell differential ionization probability of argon for scattering angles up to 90^circ appears to be no more than the molecular effect in the total ionization probability. The uncertainity in our results is statistical in nature and can be improved upon by running the experiment for a longer duration of time.

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

    PubMed

    Scholes, Natalie S; Weinzierl, Robert O J

    2016-05-01

    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

  10. 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

  11. 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

  12. 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

  13. Molecular modeling studies of interactions between sodium polyacrylate polymer and calcite surface

    NASA Astrophysics Data System (ADS)

    Ylikantola, A.; Linnanto, J.; Knuutinen, J.; Oravilahti, A.; Toivakka, M.

    2013-07-01

    The interactions between calcite pigment and sodium polyacrylate dispersing agent, widely used in papermaking as paper coating components, were investigated using classical force field and quantum chemical approaches. The objective was to understand interactions between the calcite surface and sodium polyacrylate polymer at 300 K using molecular dynamics simulations. A quantum mechanical ab initio Hartree-Fock method was also used to obtain detailed information about the sodium polyacrylate polymer structure. The effect of water molecules (moisture) on the interactions was also examined. Calculations showed that molecular weight, branching and the orientation of sodium polyacrylate polymers influence the interactions between the calcite surface and the polymer. The force field applied, and also water molecules, were found to have an impact on all systems studied. Ab initio Hartree-Fock calculations indicated that there are two types of coordination between sodium atoms and carboxylate groups of the sodium polyacrylate polymer, inter- and intra-carboxylate group coordination. In addition, ab initio Hartree-Fock calculations of the structure of the sodium polyacrylate polymer produced important information regarding interactions between the polymers and carboxylated styrene-butadiene latex particles.

  14. Investigation of protein-ligand interactions by mass spectrometry.

    PubMed

    Sinz, Andrea

    2007-04-01

    The rate of drug discovery is greatly dependent on the development and improvement of rapid and reliable analytical methods that allow screening for protein-ligand interactions. The solution-based methods for investigating protein-ligand interactions by mass spectrometry (MS), which are discussed in this paper, are hydrogen/deuterium exchange of protein backbone amide hydrogens, and photoaffinity labeling. Moreover, MS analysis of intact noncovalent protein-ligand complexes is described. Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) with its ultra-high resolution and excellent mass accuracy is also considered herein as it is gaining increasing popularity for a mass spectrometric investigation of protein-ligand interactions. PMID:17299828

  15. Protein lethality investigated in terms of long range dynamical interactions.

    PubMed

    Rodrigues, Francisco A; Costa, Luciano da Fontoura

    2009-04-01

    The relationship between network structure/dynamics and biological function constitutes a fundamental issue in systems biology. However, despite many related investigations, the correspondence between structure and biological functions is not yet fully understood. A related subject that has deserved particular attention recently concerns how essentiality is related to the structure and dynamics of protein interactions. In the current work, protein essentiality is investigated in terms of long range influences in protein-protein interaction networks by considering simulated dynamical aspects. This analysis is performed with respect to outward activations, an approach which models the propagation of interactions between proteins by considering self-avoiding random walks. The obtained results are compared to protein local connectivity. Both the connectivity and the outward activations were found to be strongly related to protein essentiality. PMID:19396375

  16. Investigating correlation between verbal interactions and perceived stress.

    PubMed

    Ferdous, Raihana; Osmani, Venet; Beltran Marquez, Jessica; Mayora, Oscar

    2015-08-01

    While moderate exposure to stress at work can act as productivity booster, prolonged exposure not only decreases productivity, but it can also lead to an array of health related problems. Therefore, monitoring stress levels and more importantly correlated stressors, becomes prerequisite for a productive workforce. Considering that verbal interaction is an integral part of workplace environments, we report the results of our study that investigates correlation between perceived stress levels and verbal interaction. 28 workers were monitored over 6 weeks through their smartphones during their daily, real-world behaviour, capturing both verbal interaction and perceived stress levels. Results show that more than half of participants show correlation between perceived stress levels and verbal interaction, while this correlation is observed for over 90% of highly stressed participants. PMID:26736583

  17. 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.

  18. On-chip investigation of cell-drug interactions.

    PubMed

    Zheng, Xin Ting; Yu, Ling; Li, Peiwu; Dong, Hua; Wang, Yingjun; Liu, Yun; Li, Chang Ming

    2013-11-01

    Investigation of cell-drug interaction is of great importance in drug discovery but continues to pose significant challenges to develop robust, fast and high-throughput methods for pharmacologically profiling of potential drugs. Recently, cell chips have emerged as a promising technology for drug discovery/delivery, and their miniaturization and flow-through operation significantly reduce sample consumption while dramatically improving the throughput, reliability, resolution and sensitivity. Herein we review various types of miniaturized cell chips used in investigation of cell-drug interactions. The design and fabrication of cell chips including material selection, surface modification, cell trapping/patterning, concentration gradient generation and mimicking of in vivo environment are presented. Recent advances of on-chip investigations of cell-drug interactions, in particular the high-throughput screening, cell sorting, cytotoxicity testing, drug resistance analysis and pharmacological profiling are examined and discussed. It is expected that this survey can provide thoughtful basics and important applications of on-chip investigations of cell-drug interactions, thus greatly promoting research and development interests in this area. PMID:23428898

  19. 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…

  20. Molecular Structure and Interactions in the Ionic Liquid 1-Ethyl-3-methylimidazolium Trifluoromethanesulfonate.

    PubMed

    Singh, Dheeraj K; Rathke, Bernd; Kiefer, Johannes; Materny, Arnulf

    2016-08-11

    Quantum chemical theory (DFT and MP2) and vibrational spectroscopy (ATR-IR and Raman) were employed to investigate the electronic structure and molecular interactions in the room-temperature ionic liquid 1-ethyl-3-methylimidazolium trifluoromethanesulfonate. Various possible conformers of a cation-anion pair based on their molecular interactions were simulated in the gas phase. All the different theoretical (MP2, B3LYP, and the dispersion-corrected wB97XD) methods assume the same ion-pair conformation for the lowest energy state. Basis set superimpose error (BSSE) correction was also introduced by using the counterpoise method. Strong C-H···O interactions between the most acidic hydrogen atom of the cation imidazole ring (C2H) and the oxygen atom of the anion were predicted where the anion is located at the top of (C2H). In this case, methyl and alkyl groups also interact with the anion in the form of a C-H···O hydrogen bond. Interestingly, the dispersion-corrected methodology neglects the C4/C5-H···O and C-H···F interaction in the ion-pair calculations. The theoretical results were compared with the experimental observations from Raman scattering and ATR-IR absorption spectroscopy, and the predictions of the molecular interactions in the vibrational spectra were discussed. The wavenumber shifts of the characteristic vibrations relative to the free cation and anion are explained by estimating the geometric parameters as well as the difference in the natural bond orbital (NBO) charge density. PMID:27429245

  1. Investigation of the interaction between naringin and human serum albumin

    NASA Astrophysics Data System (ADS)

    Zhang, Yaheng; Li, Ying; Dong, Lijun; Li, Jiazhong; He, Wenying; Chen, Xingguo; Hu, Zhide

    2008-03-01

    The interaction between naringin and human serum albumin (HSA) has been thoroughly studied by fluorescence quenching technique in combination with UV absorption spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, circular dichroism (CD) spectroscopy and molecular modeling method. Under the simulative physiological conditions, fluorescence data revealed the presence of the binding site on HSA and its binding constants ( K) are 1.62 × 10 4, 1.68 × 10 4, 1.72 × 10 4, and 1.79 × 10 4 M -1 at 289, 296, 303, and 310 K, respectively. The alterations of protein secondary structure in the presence of naringin aqueous solution were qualitative and quantitative calculated by the evidence from CD and FT-IR spectroscopes. In addition, according to the Van't Hoff equation, the thermodynamic functions standard enthalpy (Δ H0) and standard entropy (Δ S0) for the reaction were calculated to be 3.45 kJ mol -1 and 92.52 J mol -1 K -1. These results indicated that naringin binds to HSA mainly by a hydrophobic interaction. Furthermore, the displacement experiments confirmed that naringin could bind to the site I of HSA, which was also in agreement with the result of the molecular modeling study.

  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. Molecular interaction mechanism between 2-mercaptobenzimidazole and copper-zinc superoxide dismutase.

    PubMed

    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

  5. Dissolution mechanism of cellulose in N,N-dimethylacetamide/lithium chloride: revisiting through molecular interactions.

    PubMed

    Zhang, Chao; Liu, Ruigang; Xiang, Junfeng; Kang, Hongliang; Liu, Zhijing; Huang, Yong

    2014-08-01

    Understanding the interactions between solvent molecules and cellulose at a molecular level is still not fully achieved in cellulose/N,N-dimethylacetamide (DMAc)/LiCl system. In this paper, cellobiose was used as the model compound of cellulose to investigate the interactions in cellulose/DMAc/LiCl solution by using Fourier transform infrared spectroscopy (FTIR), (13)C, (35)Cl, and (7)Li nuclear magnetic resonance (NMR) spectroscopy and conductivity measurements. It was found that when cellulose is dissolved in DMAc/LiCl cosolvent system, the hydroxyl protons of cellulose form strong hydrogen bonds with the Cl(-), during which the intermolecular hydrogen bonding networks of cellulose is broken with simultaneous splitting of the Li(+)-Cl(-) ion pairs. Simultaneously, the Li(+) cations are further solvated by free DMAc molecules, which accompany the hydrogen-bonded Cl(-) to meet electric balance. Thereafter, the cellulose chains are dispersed in molecular level in the solvent system to form homogeneous solution. This work clarifies the interactions in the cellulose/DMAc/LiCl solution at molecular level and the dissolution mechanism of cellulose in DMAc/LiCl, which is important for understanding the principle for selecting and designing new cellulose solvent systems. PMID:25026263

  6. Hadronic Scenarios for Gamma-Ray Emission from Three Supernova Remnants Interacting with Molecular Clouds

    NASA Astrophysics Data System (ADS)

    Yu, Huan; Fang, Jun; Zhang, Li

    2014-04-01

    GeV γ-rays detected with the large area telescope on board the Fermi Gamma-ray space telescope in the direction of HB21, MSH 17-39 and G337.0-0.1 have been recently reported. The three supernova remnants (SNRs) show interactions with molecular clouds, and they are effective gamma-ray emitters as the relativistic protons accelerated by the SNR shocks inelastically colliding with the dense gas in the clouds. The origin of the observed γ-rays for the three remnants is investigated in the scenario of the diffusive shock acceleration. In the model, a part of the SNR shock transmits into the nearby molecular clouds, and the shock velocity is greatly reduced. As a result, a shock with a relatively low Alfvén Mach number is generated, and the spectra of the accelerated protons and the γ-ray photons produced via proton-proton interaction can be obtained. The results show that the observed γ-ray spectra for the three SNRs interacting with the molecular clouds can be reproduced. It can be concluded that the hadronic origin of the γ-rays for the three SNRs is approved, and the ability of SNR shocks to accelerate protons is also supported.

  7. 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

  8. 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.

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

    PubMed

    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

  10. 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

  11. 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.

  12. An in situ study of amine and amide molecular interaction on Fe surfaces

    NASA Astrophysics Data System (ADS)

    Taheri, P.; Terryn, H.; Mol, J. M. C.

    2015-11-01

    The interfacial bondings formed between N,N‧-diethylmethylamine, N-methyldiethanolamine and N,N‧-dimethylsuccinamide molecules with iron surfaces have been investigated using Fourier transform infrared spectroscopy (FTIR) and electrochemical spectroscopies. In this case, the interfacial interactions have been evaluated by analyzing ex situ FTIR peaks and probing potential variations upon molecular interactions to Fe surfaces. Moreover, integrated ATR-FTIR and chronovoltammetry analyses in Kretschmann geometry have been employed to probe the interactions between the molecules and Fe surfaces in situ. The results revealed that a charge transfer between molecules and Fe surfaces takes place indicating chemisorption of the molecules on Fe surfaces. In this case, the interaction of N,N‧-diethylmethylamine and Fe surface is negligible. However, N-methyldiethanolamine molecules interact with Fe surfaces through the nitrogen atoms. Interaction of N,N‧-dimethylsuccinamide molecules and Fe surface is promoted by nitrogen and carbonyl functional groups. Moreover, interactions of N-methyldiethanolamine and N,N‧-dimethylsuccinamide molecules to Fe surfaces are encouraged by application of anodic potentials implying that the molecules and Fe surfaces are charged positively and negatively, respectively.

  13. 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

  14. Internalization and molecular interactions of human CD21 receptor.

    PubMed

    Tessier, Jacques; Cuvillier, Armelle; Glaudet, Florence; Khamlichi, Ahmed Amine

    2007-03-01

    The human CD21 is a receptor for cleavage fragments of the third complement component and for Epstein-Barr virus. Previous mutational studies showed that the cytoplasmic domain of CD21 is absolutely required for internalization of either ligand. With the exception of CD19, CD81, Leu-13 and CD35 that can form a complex with CD21 at the cell surface, no other partner that interacts with the hCD21 transmembrane or the cytoplasmic domain was identified. We investigated the internalization capacity of hCD21 tail mutants in the absence of B cell receptor cross-linking by using stable murine B cell transfectants. We provide evidence that at least two internalization motifs are activated when hCD21 binds a monoclonal antibody. In order to identify the cellular proteins that interact with the hCD21 transmembrane and cytoplasmic domains, we combined a mutational mapping with a two-hybrid system approach both in yeast and in mammalian cells. We identified four novel partners that are involved in intracellular trafficking, sorting or cytoskeleton remodeling and we mapped the hCD21 transmembrane and tail subdomains they interact with. We discuss the potential physiological significance of these findings in the context of hCD21 internalization and intracellular trafficking. PMID:17118449

  15. 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

  16. Understanding Miltefosine-Membrane Interactions Using Molecular Dynamics Simulations.

    PubMed

    de Sá, Matheus Malta; Sresht, Vishnu; Rangel-Yagui, Carlota Oliveira; Blankschtein, Daniel

    2015-04-21

    Coarse-grained molecular dynamics simulations are used to calculate the free energies of transfer of miltefosine, an alkylphosphocholine anticancer agent, from water to lipid bilayers to study its mechanism of interaction with biological membranes. We consider bilayers containing lipids with different degrees of unsaturation: dipalmitoylphosphatidylcholine (DPPC, saturated, containing 0%, 10%, and 30% cholesterol), dioleoylphosphatidylcholine (DOPC, diunsaturated), palmitoyloleoylphosphatidylcholine (POPC, monounsaturated), diarachidonoylphosphatidylcholine (DAPC, polyunsaturated), and dilinoleylphosphatidylcholine (DUPC, polyunsaturated). These free energies, calculated using umbrella sampling, were used to compute the partition coefficients (K) of miltefosine between water and the lipid bilayers. The K values for the bilayers relative to that of pure DPPC were found to be 5.3 (DOPC), 7.0 (POPC), 1.0 (DAPC), 2.2 (DUPC), 14.9 (10% cholesterol), and 76.2 (30% cholesterol). Additionally, we calculated the free energy of formation of miltefosine-cholesterol complexes by pulling the surfactant laterally in the DPPC + 30% cholesterol system. The free energy profile that we obtained provides further evidence that miltefosine tends to associate with cholesterol and has a propensity to partition into lipid rafts. We also quantified the kinetics of the transport of miltefosine through the various bilayers by computing permeance values. The highest permeance was observed in DUPC bilayers (2.28 × 10(-2) m/s) and the lowest permeance in the DPPC bilayer with 30% cholesterol (1.10 × 10(-7) m/s). Our simulation results show that miltefosine does indeed interact with lipid rafts, has a higher permeability in polyunsaturated, loosely organized bilayers, and has higher flip-flop rates in specific regions of cellular membranes. PMID:25819781

  17. 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

  18. 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

  19. 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.

  20. Investigating molecular dynamics-guided lead optimization of EGFR inhibitors.

    PubMed

    Lavecchia, Martin J; Puig de la Bellacasa, Raimon; Borrell, José I; Cavasotto, Claudio N

    2016-02-15

    The epidermal growth factor receptor (EGFR) is part of an extended family of proteins that together control aspects of cell growth and development, and thus a validated target for drug discovery. We explore in this work the suitability of a molecular dynamics-based end-point binding free energy protocol to estimate the relative affinities of a virtual combinatorial library designed around the EGFR model inhibitor 6{1} as a tool to guide chemical synthesis toward the most promising compounds. To investigate the validity of this approach, selected analogs including some with better and worse predicted affinities relative to 6{1} were synthesized, and their biological activity determined. To understand the binding determinants of the different analogs, hydrogen bonding and van der Waals contributions, and water molecule bridging in the EGFR-analog complexes were analyzed. The experimental validation was in good qualitative agreement with our theoretical calculations, while also a 6-dibromophenyl-substituted compound with enhanced inhibitory effect on EGFR compared to the reference ligand was obtained. PMID:26810832

  1. 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

  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. 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. PMID:24693489

  4. CELLULAR AND MOLECULAR INTERACTIONS OF PHOSPHOINOSITIDES AND PERIPHERAL PROTEINS

    PubMed Central

    Stahelin, Robert V.; Scott, Jordan L.; Frick, Cary T.

    2015-01-01

    Anionic lipids act as signals for the recruitment of proteins containing cationic clusters to biological membranes. A family of anionic lipids known as the phosphoinositides (PIPs) are low in abundance, yet play a critical role in recruitment of peripheral proteins to the membrane interface. PIPs are mono-, bis-, or trisphosphorylated derivatives of phosphatidylinositol (PI) yielding seven species with different structure and anionic charge. The differential spatial distribution and temporal appearance of PIPs is key to their role in communicating information to target proteins. Selective recognition of PIPs came into play with the discovery that the substrate of protein kinase C termed pleckstrin possessed the first PIP binding region termed the pleckstrin homology (PH) domain. Since the discovery of the PH domain, more than ten PIP binding domains have been identified including PH, ENTH, FYVE, PX, and C2 domains. Representative examples of each of these domains have been thoroughly characterized to understand how they coordinate PIP headgroups in membranes, translocate to specific membrane docking sites in the cell, and function to regulate the activity of their full-length proteins. In addition, a number of novel mechanisms of PIP-mediated membrane association have emerged, such as coincidence detection – specificity for two distinct lipid headgroups. Other PIP-binding domains may also harbor selectivity for a membrane physical property such as charge or membrane curvature. This review summarizes the current understanding of the cellular distribution of PIPs and their molecular interaction with peripheral proteins. PMID:24556335

  5. Novel molecular beacon DNA probes for protein-nucleic acid interaction studies

    NASA Astrophysics Data System (ADS)

    Li, Jianwei J.; Perlette, John; Fang, Xiaohong; Kelley, Shannon; Tan, Weihong

    2000-03-01

    We report a novel approach to study protein-nucleic acid interactions by using molecular beacons (MBs). Molecular beacons are hairpin-shaped DNA oligonucleotide probes labeled with a fluorophore and a quencher, and can report the presence of target DNA/RNA sequences. MBs can also report the existence of single-stranded DNA binding proteins (SSB) through non-sequence specific binding. The interaction between SSB and MB has resulted in significant fluorescence restoration of the MB. The fluorescence enhancement brought by SSB and by complementary DNA is very comparable. The molar ratio of the binding between SSB and the molecular beacon is 1:1 with a binding constant of 2 X 107 M-1. Using the MB-SSB binding, we are able to determine SSB at 2 X 10-10 M with a conventional spectrometer. We have also applied MB DNA probes for the analysis of an enzyme lactic dehydrogenase (LDH), and for the investigation of its binding properties with ssDNA. The biding process between MB and different isoenzymes of LDH has been studied. We also show that there are significant differences in MB binding affinity to different proteins, which will enable selective binding studies of a variety of proteins. This new approach is potentially useful for protein-DNA/RNA interaction studies that require high sensitivity, speed and convenience. The results also open the possibility of using easily obtainable, custom designed, modified DNA molecules for studies of drug interactions and targeting. Our results demonstrate that MB can be effectively used for sensitive protein quantitation and for efficient protein-DNA interaction studies. MB has the signal transduction mechanism built within the molecule, and can thus be used for quick protein assay development and for real-time measurements.

  6. 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

  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. Temperature effect on the molecular interactions between ammonium ionic liquids and N,N-dimethylformamide.

    PubMed

    Attri, Pankaj; Venkatesu, Pannuru; Kumar, Anil

    2010-10-28

    In view of the wide scope of molecular interactions between the highly polar compound of N,N-dimethylformamide (DMF) and ammonium ionic liquids (ILs), we have measured thermophysical properties such as densities (ρ) and ultrasonic sound velocities (u) over the whole composition range at temperatures ranging from 25 to 50 °C under atmospheric pressure. To gain some insight into the several aggregations of molecular interactions present in these mixed solvents, we predicted the excess molar volume (V(E)) and the deviations in isentropic compressibilities (ΔK(s)) as a function of the concentration of IL. These results are fitted to the Redlich-Kister polynomials. The materials investigated in the present study included the hydroxide series of ammonium ILs of tetramethylammonium hydroxide [(CH(3))(4)N][OH] (TMAH), tetraethylammonium hydroxide [(C(2)H(5))(4)N][OH] (TEAH), and tetrapropylammonium hydroxide [(C(2)H(7))(4)N][OH] (TPAH). The intermolecular interactions and structural effects were analyzed on the basis of the measured and the derived properties. A qualitative analysis of the results is discussed in terms of the ion-dipole and ion-pair interactions, and hydrogen bonding between ILs and DMF molecules and their structural factors. PMID:20925365

  10. 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

  11. 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

  12. 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.

  13. Evaluating the Molecular Interaction of Organic Liquid Mixtures Using Near-Infrared Spectroscopy.

    PubMed

    Xiong, Zhixin; Pfeifer, Frank; Siesler, Heinz W

    2016-04-01

    The near-infrared transmission spectra of two organic liquid three-component systems of variable compositions were investigated in detail. To evaluate the interaction of the different components in the two systems the experimental spectra of the pure components were compared to mathematically constructed "pure component" spectra. Though usually the correlation coefficient (CC) and Manhattan distance (MD) are used to measure the similarity of spectra, in the present investigations principal component analysis (PCA) was found to be a more effective tool to investigate the difference between these spectra and derive parameters characterizing the interaction between the different components. Thus, PC scores for the two types of spectra established some distinct patterns which clearly expressed their differences. For a three-dimensional coordinate system of selected principal components, the Euclidean distances between the mathematically constructed and the experimental spectra of the pure components were calculated. Finally, the mean values of the distances for each component provided indices to rank the interaction of the components in the mixtures. Thus, the results offer a convenient approach that can quantitatively evaluate the molecular interactions of the individual components in organic liquid mixtures by various spectroscopies. PMID:26928223

  14. 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.

  15. 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 ...

  16. 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

  17. 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.

  18. 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

  19. 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

  20. Lipid-based nanocarrier for quercetin delivery: system characterization and molecular interactions studies.

    PubMed

    Hädrich, Gabriela; Monteiro, Samantha Oliveira; Rodrigues, Marisa Raquel; de Lima, Vânia Rodrigues; Putaux, Jean-Luc; Bidone, Juliana; Teixeira, Helder Ferreira; Muccillo-Baisch, Ana Luiza; Dora, Cristiana Lima

    2016-07-01

    The flavonoid quercetin (QU) is a naturally occurring compound with several biological activities. However, the oral bioavailability of this compound is very low due to the high pre-systemic metabolism in the colon and liver and its low water solubility. In this context, the development of QU-loaded nanocarriers (NEs) is a promising approach to improve the drug oral bioavailability. This study investigates the variation of the concentration of 12-hydroxystearic acid-polyethylene glycol copolymer, lecithin and castor oil (CO) as to increase the amount of QU encapsulated while maintaining physicochemical characteristics described in previous studies. To better understand the ability to load and release the drug, we investigated the molecular interactions between QU and NE. Lipid-based NEs were prepared using CO as oily phase and PEG 660-stearate and lecithin as surfactants. Hot solvent diffusion and phase inversion temperature were methods employed to produce NEs. The QU-NEs were investigated for physicochemical characteristics and in vitro drug release. Molecular interactions between QU and the NEs were monitored through the complementary infrared (Fourier transform infrared) and NMR. The results revealed that it was possible to incorporate higher amounts of QU in a lipid-based NE with a reduced size (20 nm). The system developed allow a sustained release of QU probably due to the shell formed by the surfactants around the NE and the flavonoid ordering effect in the emulsion hydrophobic regions, which may reduce the system permeability. PMID:26571009

  1. Replicas of the Kondo peak due to electron-vibration interaction in molecular transport properties

    NASA Astrophysics Data System (ADS)

    Roura-Bas, P.; Tosi, L.; Aligia, A. A.

    2016-03-01

    The low temperature properties of single level molecular quantum dots including both electron-electron and electron-vibration interactions, are theoretically investigated. The calculated differential conductance in the Kondo regime exhibits not only the zero bias anomaly but also side peaks located at bias voltages which coincide with multiples of the energy of vibronic mode V ˜ℏ Ω /e . We obtain that the evolution with temperature of the two main satellite conductance peaks follows the corresponding one of the Kondo peak when ℏ Ω ≫kBTK , TK being the Kondo temperature, in agreement with recent transport measurements in molecular junctions. However, we find that this is no longer valid when ℏ Ω is of the order of a few times kBTK .

  2. Molecular interaction studies of hemostasis: fibrinogen ligand-human platelet receptor interactions.

    PubMed

    Lee, Imshik; Marchant, Roger E

    2003-01-01

    The interactions between fibrinogen ligands and platelet receptor alpha(IIb)beta(3) were studied under physiological conditions by atomic force microscopy (AFM). Two linear peptide sequences in fibrinogen, RGD and HHLGGAKQAGDV, play central roles in the regulation of hemostasis and thrombosis by facilitating adhesion and aggregation of platelets. In order to measure the interactions (i.e., debonding force), oligopeptides, GSSSGaaa, where aaa is -RGDSPA or -HHLGGAKQAGDV, were synthesized and grafted on to the surface of AFM probe tips. The interaction forces between a peptide-modified AFM probe tip and platelet surface were determined from pN to nN levels using AFM force measurements. Our results show that the zero kinetic off-rate, K(off)(0), for RGDSPA is significantly smaller than that for HHLGGAKQAGDV, under the consideration of flexible receptor surfaces. From our analysis, the K(off)(0), the single molecular binding energy E(b), and the transition state x(b), were extracted from the data, and estimated to be 1.53s(-1), -2.64x10(-20)J and 1.03A for the RGD-alpha(IIb)beta(3) system, and 47.58s(-1), 2.67x10(-20), 1.09A for the HHLGGAKQAGDV-alpha(IIb)beta(3) system, respectively. PMID:12801687

  3. Intermolecular Sulfur···Oxygen Interactions: Theoretical and Statistical Investigations.

    PubMed

    Zhang, Xuejin; Gong, Zhen; Li, Jian; Lu, Tao

    2015-10-26

    Intermolecular S···O interactions are very common and are important in biological systems, but until recently, the presence of these contacts in protein-ligand systems largely depended on serendipitous discovery instead of rational design. Here we provide insight into the phenomenon of intermolecular S···O contacts by focusing on three sulfur-containing aromatic rings. Quantum mechanics is employed to characterize the strength and directionality of the S···O interactions and to determine their energy dependence on their geometric parameters. Protein Data Bank mining is performed to systematically determine the occurrence and geometry of intermolecular S···O interactions, and several representative examples are discussed. Three typical cases are investigated using a combined quantum mechanics/molecular mechanics approach to demonstrate the potential of these interactions in improving binding affinities and physiochemical properties. Overall, our work elucidates the structures and energy features of intermolecular S···O interactions and addresses their use in molecular design. PMID:26393532

  4. Molecular dynamics of interactions of rice with rice blast and sheath blight pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In an effort to develop the molecular strategies to control rice (Oryzae sativa) diseases, molecular interactions of rice with rice blast [Magnaporthe oryzae, formerly (Magnaporthe grisea] and sheath blight (Rhizoctonia solani) fungi were analyzed. The interaction of rice with M. oryzae follows a b...

  5. 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.

  6. 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.

  7. Precritical State Transition Dynamics in the Attractor Landscape of a Molecular Interaction Network Underlying Colorectal Tumorigenesis

    PubMed Central

    Cho, Kwang-Hyun

    2015-01-01

    From the perspective of systems science, tumorigenesis can be hypothesized as a critical transition (an abrupt shift from one state to another) between proliferative and apoptotic attractors on the state space of a molecular interaction network, for which an attractor is defined as a stable state to which all initial states ultimately converge, and the region of convergence is called the basin of attraction. Before the critical transition, a cellular state might transit between the basin of attraction for an apoptotic attractor and that for a proliferative attractor due to the noise induced by the inherent stochasticity in molecular interactions. Such a flickering state transition (state transition between the basins of attraction for alternative attractors from the impact of noise) would become more frequent as the cellular state approaches near the boundary of the basin of attraction, which can increase the variation in the estimate of the respective basin size. To investigate this for colorectal tumorigenesis, we have constructed a stochastic Boolean network model of the molecular interaction network that contains an important set of proteins known to be involved in cancer. In particular, we considered 100 representative sequences of 20 gene mutations that drive colorectal tumorigenesis. We investigated the appearance of cancerous cells by examining the basin size of apoptotic, quiescent, and proliferative attractors along with the sequential accumulation of gene mutations during colorectal tumorigenesis. We introduced a measure to detect the flickering state transition as the variation in the estimate of the basin sizes for three-phenotype attractors from the impact of noise. Interestingly, we found that this measure abruptly increases before a cell becomes cancerous during colorectal tumorigenesis in most of the gene mutation sequences under a certain level of stochastic noise. This suggests that a frequent flickering state transition can be a precritical

  8. 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.

  9. 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

  10. Investigating Atmospheric Oxidation with Molecular Dynamics Imaging and Spectroscopy

    NASA Astrophysics Data System (ADS)

    Merrill, W. G.; Case, A. S.; Keutsch, F. N.

    2013-06-01

    Volatile organic compounds (VOCs) in the Earth's atmosphere constitute trace gas species emitted primarily from the biosphere, and are the subject of inquiry for a variety of air quality and climate studies. Reactions intiated (primarily) by the hydroxyl radical (OH) lead to a myriad of oxygenated species (OVOCs), which in turn are prone to further oxidation. Investigations of the role that VOC oxidation plays in tropospheric chemistry have brought to light two troubling scenarios: (1) VOCs are responsible in part for the production of two EPA-regulated pollutants---tropospheric ozone and organic aerosol---and (2) the mechanistic details of VOC oxidation remain convoluted and poorly understood. The latter issue hampers the implementation of near-explicit atmospheric simulations, and large discrepancies in OH reactivity exist between measurements and models at present. Such discrepancies underscore the need for a more thorough description of VOC oxidation. Time-of-flight measurements and ion-imaging techniques are viable options for resolving some of the mechanistic and energetic details of VOC oxidation. Molecular beam studies have the advantage of foregoing unwanted bimolecular reactions, allowing for the characterization of specific processes which must typically compete with the complex manifold of VOC oxidation pathways. The focus of this work is on the unimolecular channels of organic peroxy radical intermediates, which are necessarily generated during VOC oxidation. Such intermediates may isomerize and decompose into distinct chemical channels, enabling the unambiguous detection of each pathway. For instance, a (1 + 1') resonance enhanced multiphoton ionization (REMPI) scheme may be employed to detect carbon monoxide generated from a particular unimolecular process. A number of more subtle mechanistic details may be explored as well. By varying the mean free path of the peroxy radicals in a flow tube, the role of collisional quenching in these unimolecular

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Molecular dynamics simulation of interaction of H with vacancy in W

    SciTech Connect

    Li, Xiaochun; Gao, Fei; Lu, Guang-Hong

    2009-09-15

    Molecular dynamics simulations were performed to investigate the interaction between H and vacancy in W using an analytical bond-order potential to describe the interactions between W-W, W-H and H-H. The most stable configuration for H in W is the tetrahedron interstitial site. We calculated the binding energies of an H and a vacancy to an H-vacancy cluster (HnVm) in W, respectively, where n and m ranged from 0 to 10. The binding energy was almost unchanged. The binding energy of a vacancy to H-vacancy cluster is about 0.4eV, which is higher than the binding energy of an H to H-vacancy cluster. Vacancy is much easier to binding with H-vacancy cluster than H. And H is easier to stay in the tetrahedron interstitial site or octahedron interstitial site in bcc W.

  17. "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

  18. 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.

  19. First Principles Investigation of the C3 Coefficients for Molecular Adsorption on Transition Metal Surfaces

    NASA Astrophysics Data System (ADS)

    Kara, Abdelkader; Matos, Jeronimo; Yildirim, Handan

    2015-03-01

    C6 coefficients are used to investigate the strength of the long-range interactions for weakly interacting dimers as a function of separation distance. These coefficients are useful both as a measure for the accuracy of the various van der Waals (vdW) inclusive methods as well as reference for use in large-scale molecular dynamics simulations. In the case of molecule-surface interaction, the C3 coefficient is the counterpart to the C6 coefficient that is used for testing the interaction of dimers. We will present the results of the vdW inclusive density functional theory (DFT) calculations evaluating the C3 coefficients for the adsorption of M/X(110) and X(111), with X: Ag, Au, Cu, Pt, Pd, Ni, Rh and M: Benzene, Thiophene, Sexithiophene, Pentacene and Olympicene, as described by the PBE exchange-correlation functional and the self-consistent vdW-DF, optimized vdW-DFs and vdW-DF2 functionals. Work supported by the U.S. Department of Energy Basic Energy Science under Contract No. DE-FG02-11ER16243.

  20. The emergence of flow cytometry for sensitive, real-time measurements of molecular interactions

    SciTech Connect

    Nolan, J.P.; Sklar, L.A. |

    1998-07-01

    The analysis of macromolecular interactions is an essential element of biomedical research. Flow cytometry is uniquely capable of making sensitive and quantitative measurements of molecular interactions. These measurements can be made in real time with subsecond kinetic resolution using purified biomolecules or living cells. Combined with automated sample handling, these features make flow cytometry a versatile and robust technology for the analysis of molecular interactions.

  1. Interaction of staphylokinase with different molecular forms of plasminogen.

    PubMed

    Lijnen, H R; Van Hoef, B; Collen, D

    1993-01-15

    In order to obtain more information on the mechanism of plasminogen activation by staphylokinase (STA), we have studied the interaction between recombinant STA (STAR) and different molecular forms of human plasminogen, including Glu-plasminogen (native moiety), Lys-plasminogen (partially degraded moiety) and low-molecular-mass (LMM) plasminogen (moiety lacking kringles 1-4). Addition of 2 microM STAR to 0.4 microM Glu-plasminogen, Lys-plasminogen or LMM plasminogen resulted in the generation of proteolytic activity towards the chromogenic substrate D-Val-Leu-Lys-NH-PhNO2 (S-2251) corresponding to the exposure of 1 active center/plasminogen molecule. Complex formation was associated with conversion of the one-chain plasminogen moieties to two-chain plasmin, and with quantitative conversion of Glu-plasminogen to Lys-plasmin. The stoichiometry of the plasminogen-STAR complex, determined by binding of the complex to Lys-Sepharose and measurement of residual STAR, was found to be equimolar. The plasminogen-STAR complexes were inhibited by alpha 2-antiplasmin with second-order rate constants of 2.4 +/- 0.17 x 10(6) M-1 s-1 for Glu-plasminogen, 2.4 +/- 0.21 x 10(6) M-1 s-1 for Lys-plasminogen and 9.4 +/- 1.5 x 10(4) M-1 s-1 for LMM plasminogen. Glu-plasmin-STAR, Lys-plasmin-STAR and LMM plasmin-STAR had comparable catalytic efficiencies (kcat/Km) for the activation of Glu-plasminogen (0.24-0.29 microM-1 s-1), Lys-plasminogen (0.57-0.79 microM-1 s-1) or LMM plasminogen (0.11-0.16 microM-1 s-1). In a human plasma milieu in vitro STAR, Glu-plasmin-STAR, Lys-plasmin-STAR and LMM-plasmin-STAR were equally effective for the lysis of 125I-fibrin-labeled human plasma clots [50% clot lysis in 2 h (EC50) with 11-13 nM test compound] and equally fibrin-selective (residual fibrinogen levels of 72-84% after 2 h at EC50). Our results thus confirm that plasminogen and STAR form a 1:1 stoichiometric complex in which plasminogen is converted to plasmin and Glu-plasminogen to Lys

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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

  9. A calorimetric investigation of doxorubicin-polymer bead interactions.

    PubMed

    Waters, Laura J; Swaine, Tanya S; Lewis, Andrew L

    2015-09-30

    Isothermal titration calorimetry (ITC) was utilised to investigate suitability of the technique to determine the stoichiometry and thermodynamics of the interactions that occur between a commonly used chemotherapeutic drug, namely doxorubicin, and a polymer bead-based drug delivery embolisation system (DC Bead™). Six temperatures were selected for drug-polymer titrations (293-313 K) and in all cases an initially exothermic signal reverted to an endothermic response upon the saturation of the beads with drug. From these experiments, and subsequent calculations, the molar ratio of drug to SO3(-) (polymer) was found to be 0.4:1 at all temperatures studied. Enthalpic data was calculated from the raw ITC data with an average enthalpy of drug-polymer binding of - 14.8 kJ mol(-1) at 293 K through to - 19.4 kJ mol(-1) at 313 K implying the process is enthalpically-driven yet only affected by an increase in experimental temperature to a limited extent whereby an increase in experimental temperature results in a small increase in the negativity in change in enthalpy recorded. The application of ITC in this study (with its unique ability to monitor real-time interactions and facilitate stoichiometric calculations) resolves the lack of knowledge regarding the thermodynamics of this specific drug-polymer interaction. This study confirms that ITC is not only useful for this specific system, but also highlights the potential use of ITC for more general studies in this area. PMID:26209073

  10. 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.

  11. 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.

  12. 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.

  13. Molecular Interactions of Alzheimer Amyloid-β Oligomer with Neutral and Negatively Charged Lipid Bilayers

    PubMed Central

    Yu, Xiang; Wang, Qiuming; Pan, Qingfen; Zhou, Feimeng; Zheng, Jie

    2013-01-01

    Interaction of p3 (Aβ17-42) peptides with cell membrane is crucial for the understanding of amyloid toxicity associated with Alzheimer’s disease (AD). Such p3-membrane interactions are considered to induce the disruption of membrane permeability and integrity, but the exact mechanisms of how p3 aggregates, particularly small p3 oligomers, induce receptor-independent membrane disruption are not yet completely understood. Here, we investigate the adsorption, orientation, and surface interaction of the p3 pentamer with lipid bilayers composed of both pure zwitterionic POPC (palmitoyl-oleyl-phosphatidylcholine) and mixed anionic POPC/POPG (palmitoyl-oleyl-phosphatidylglycerol) (3:1) lipids using explicit-solvent molecular dynamics (MD) simulations. MD simulation results show that the p3 pentamer has much stronger interactions with mixed POPC/POPG lipids than pure POPC lipids, consistent with experimental observation that Aβ adsorption and fibrililation are enhanced on anionic lipid bilayers. Although electrostatic interactions are main attractive forces to drive the p3 to adsorb on the bilayer surface, the adsorption of the p3 pentamer on the lipid bilayer with a preferential C-terminal β-strands facing toward the bilayer surface is a net outcome of different competitions between p3 peptides-lipid bilayer and ions-p3-bilayer interactions. More importantly, Ca2+ ions are found to form ionic bridges to associate negatively charged residues of p3 with anionic headgroups of the lipid bilayer, resulting in Aβ–Ca2+–PO4− complexes. Intensive Ca2+ bound to lipid bilayer and Ca2+ ionic bridges may lead to the alternation of Ca2+ hemostasis responsible for neuronal dysfunction and death. This work provides insights into the mutual structure, dynamics, and interactions of both Aβ peptides and lipid bilayer at the atomic level, which expand our understanding of the complex behavior of amyloid-induced membrane disruption. PMID:23493873

  14. Protein-protein interaction studies based on molecular aptamers by affinity capillary electrophoresis.

    PubMed

    Huang, Chih-Ching; Cao, Zehui; Chang, Huan-Tsung; Tan, Weihong

    2004-12-01

    Protein-DNA/protein-protein interactions play critical roles in many biological processes. We report here the investigation of protein-protein interactions using molecular aptamers with affinity capillary electrophoresis (ACE). A human alpha-thrombin binding aptamer was labeled with 6-carboxyfluorescein and exploited as a selective fluorescent probe for studying thrombin-protein interactions using capillary electrophoresis with laser-induced fluorescence. A 15-mer binding DNA aptamer can be separated into two peaks in CE that correspond to the linear aptamer (L-Apt) and the thrombin-binding G-quadruplex structure in the presence of K(+) or Ba(2+). In a bare capillary, the peak area of G-quadruplex aptamer (G-Apt) was found to decrease with the addition of thrombin while that of L-Apt remained unchanged. Even though the peak of the G-Apt/thrombin binding complex is broad due to a weaker binding affinity between aptamer and thrombin, we were still able to quantify the thrombin and anti-thrombin proteins (human anti-thrombin III, AT III) based on the peak areas of free G-Apt. The detection limits of thrombin and AT III were 9.8 and 2.1 nM, respectively. The aptamer-based competitive ACE assay has also been applied to quantify thrombin-anti-thrombin III interaction and to monitor this reaction in real time. The addition of poly(ethylene glycol) to the sample matrix stabilized the complex of the G-Aptthrombin. This assay can be used to study the interactions between thrombin and proteins that do not disrupt G-Apt binding property at Exosit I site of the thrombin. Our aptamer-based ACE assay can be an effective approach for studying protein-protein interactions and for analyzing binding site and binding constant information in protein-protein and protein-DNA interaction studies. PMID:15571349

  15. Interaction of dislocations with carbides in BCC Fe studied by molecular dynamics

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

    In this study, the atomic processes involving the interaction of an edge dislocation with carbide precipitates in an iron matrix are investigated by molecular dynamics, utilizing two interatomic potentials (Hepburn, 2008 and Henriksson, 2013). The carbides investigated were Fe3 C and M23C6, where M was either Fe or Cr. The results from spherical precipitates were compared with rod shaped obstacles, to investigate the effect of climb in the unpinning process and the stress related to this process. The rod simulations showed a higher unpinning stress for all investigated sizes and temperatures, which indicates that climb will play a role in the unpinning phenomenon. The results showed, as previous studies, a decrease of the unpinning stress with increasing temperature and that a larger obstacle yields a higher unpinning stress. The Orowan process of dislocation unpinning was observed with both potentials as an increase in the needed unpinning stress in consecutive interactions with the same obstacle. The results showed that the structure of the obstacle does not affect the unpinning stress, as much as temperature, for obstacles ⩾ 2 nm. Comparison of obstacles with the same structure but with different composition, Fe23C6 and Cr23C6, showed that the small shearable chromium carbides were stronger than the corresponding iron carbides, pointing to the importance of the chemical composition of the carbide.

  16. 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

  17. 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

  18. Interacting quantum fragments-rooted preorganized-interacting fragments attributed relative molecular stability of the Be(II) complexes of nitrilotriacetic acid and nitrilotri-3-propionic acid.

    PubMed

    Cukrowski, Ignacy; Mangondo, Paidamwoyo

    2016-06-01

    A method designed to investigate, on a fundamental level, the origin of relative stability of molecular systems using Be(II) complexes with nitrilotriacetic acid (NTA) and nitrilotri-3-propionic acid (NTPA) is described. It makes use of the primary and molecular fragment energy terms as defined in the IQA/F (Interacting Quantum Atoms/Fragments) framework. An extensive classical-type investigation, focused on single descriptors (bond length, density at critical point, the size of metal ion or coordination ring, interaction energy between Be(II) and a donor atom, etc.) showed that it is not possible to explain the experimental trend. The proposed methodology is fundamentally different in that it accounts for the total energy contributions coming from all atoms of selected molecular fragments, and monitors changes in defined energy terms (e.g., fragment deformation, inter- and intra-fragment interaction) on complex formation. By decomposing combined energy terms we identified the origin of relative stability of Be(II) (NTA) and Be(II) (NTPA) complexes. We found that the sum of coordination bonds' strength, as measured by interaction energies between Be(II) ion and donor atoms, favours Be(II) (NTA) but the binding energy of Be(II) ion to the entire ligand correlates well with experimental trend. Surprisingly, the origin of Be(II) (NTPA) being more stable is due to less severe repulsive interactions with the backbone of NTPA (C and H-atoms). This general purpose protocol can be employed not only to investigate the origin of relative stability of any molecular system (e.g., metal complexes) but, in principle, can be used as a predictive tool for, e.g., explaining reaction mechanism. © 2016 Wiley Periodicals, Inc. PMID:26993356

  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 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

  1. 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.

  2. IntAct: an open source molecular interaction database

    PubMed Central

    Hermjakob, Henning; Montecchi-Palazzi, Luisa; Lewington, Chris; Mudali, Sugath; Kerrien, Samuel; Orchard, Sandra; Vingron, Martin; Roechert, Bernd; Roepstorff, Peter; Valencia, Alfonso; Margalit, Hanah; Armstrong, John; Bairoch, Amos; Cesareni, Gianni; Sherman, David; Apweiler, Rolf

    2004-01-01

    IntAct provides an open source database and toolkit for the storage, presentation and analysis of protein interactions. The web interface provides both textual and graphical representations of protein interactions, and allows exploring interaction networks in the context of the GO annotations of the interacting proteins. A web service allows direct computational access to retrieve interaction networks in XML format. IntAct currently contains ∼2200 binary and complex interactions imported from the literature and curated in collaboration with the Swiss-Prot team, making intensive use of controlled vocabularies to ensure data consistency. All IntAct software, data and controlled vocabularies are available at http://www.ebi.ac.uk/intact. PMID:14681455

  3. IntAct: an open source molecular interaction database.

    PubMed

    Hermjakob, Henning; Montecchi-Palazzi, Luisa; Lewington, Chris; Mudali, Sugath; Kerrien, Samuel; Orchard, Sandra; Vingron, Martin; Roechert, Bernd; Roepstorff, Peter; Valencia, Alfonso; Margalit, Hanah; Armstrong, John; Bairoch, Amos; Cesareni, Gianni; Sherman, David; Apweiler, Rolf

    2004-01-01

    IntAct provides an open source database and toolkit for the storage, presentation and analysis of protein interactions. The web interface provides both textual and graphical representations of protein interactions, and allows exploring interaction networks in the context of the GO annotations of the interacting proteins. A web service allows direct computational access to retrieve interaction networks in XML format. IntAct currently contains approximately 2200 binary and complex interactions imported from the literature and curated in collaboration with the Swiss-Prot team, making intensive use of controlled vocabularies to ensure data consistency. All IntAct software, data and controlled vocabularies are available at http://www.ebi.ac.uk/intact. PMID:14681455

  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. 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

  6. 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.

  7. Preliminary investigations into surface molecularly imprinted nanoparticles for Helicobacter pylori eradication

    PubMed Central

    Han, Jiaying; Sun, Yinjing; Hou, Jiapeng; Wang, Yuyan; Liu, Yu; Xie, Cao; Lu, Weiyue; Pan, Jun

    2015-01-01

    This paper reports investigations into the preparation and characterization of surface molecularly imprinted nanoparticles (SMINs) designed to adhere to Helicobacter pylori (H. pylori). Imprinted nanoparticles were prepared by the inverse microemulsion polymerization method. A fraction of Lpp20, an outer membrane protein of H. pylori known as NQA, was chosen as template and modified with myristic acid to facilitate its localization on the surface of the nanoparticles. The interaction between these SMINs with the template NQA were evaluated using surface plasmon resonance (SPR), change in zeta potential and fluorescence polarization (FP). The results were highly consistent in demonstrating a preferential recognition of the template NQA for SMINs compared with the control nanoparticles. In vitro experiments also indicate that such SMINs are able to adhere to H. pylori and may be useful for H. pylori eradication. PMID:26713273

  8. Molecular Dynamics Investigation of Adhesion between TATB Surfaces and Amorphous Fluoropolymers

    SciTech Connect

    Gee, R H; Maiti, A; Bastea, S; Fried, L

    2007-01-25

    Atomistic simulations are used to study the adhesion properties of amorphous perfluoro- and fluoro-polymers onto two different crystal surfaces of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB). Properties of the bulk amorphous polymer melts are also investigated. The fluoropolymers studied in this article include Kel-F 800, Teflon{reg_sign} AF, Hyflon AD{reg_sign}, and Cytop{reg_sign}. Simulations of the bulk polymer melts were performed over a wide range of temperatures including the volumetric glass transition temperature, so as to validate the interaction parameters used. The computed glass transition temperatures and densities compare well with experiment. The solubility parameters for the various polymers also compare well with calculations based on group additive methods. The local molecular structure at the TATB interface, as well as the degree of adhesion varies from one polymer to another. All polymers except Hyflon show a propensity to readily wet the two TATB surfaces studied.

  9. Surfactant behavior of ionic liquids involving a drug: from molecular interactions to self-assembly.

    PubMed

    Tourné-Péteilh, Corine; Coasne, Benoit; In, Martin; Brevet, David; Devoisselle, Jean-Marie; Vioux, André; Viau, Lydie

    2014-02-11

    Aggregates formed in an aqueous medium by three ionic liquids CnMImIbu made up of 1-alkyl-3-methyl-imidazolium cation (n = 4, 6, 8) and ibuprofenate anion are investigated. Dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM), (1)H nuclear magnetic resonance measurements, and atom-scale molecular dynamics simulations are used to shed light on the main interactions governing the formation of the aggregates and their composition. At high concentration, mixed micelles are formed with a composition that depends on the imidazolium alkyl chain length. For the shortest alkyl chain, micelles are mainly composed of ibuprofenate anions with some imidazolium cations intercalated between the anions. Upon increasing the alkyl chain length, the composition of the aggregates gets enriched in imidazolium cations and aggregates of stoichiometric composition are obtained. Attractive interactions between these aggregates led to the formation of larger aggregates. As suggested by molecular simulations, these larger aggregates might constitute the early stage of phase separation. Transitions from micelles to vesicles or ribbons are observed due to dilution effects and changes in the chemical composition of the aggregates. We also show that aggregation can be probed using simple microscopic quantities such as radial distribution functions and average solvation numbers. PMID:24437472

  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. From protein denaturant to protectant: Comparative molecular dynamics study of alcohol/protein interactions

    NASA Astrophysics Data System (ADS)

    Shao, Qiang; Fan, Yubo; Yang, Lijiang; Qin Gao, Yi

    2012-03-01

    It is well known that alcohols can have strong effects on protein structures. For example, monohydric methanol and ethanol normally denature, whereas polyhydric glycol and glycerol protect, protein structures. In a recent combined theoretical and NMR experimental study, we showed that molecular dynamics simulations can be effectively used to understand the molecular mechanism of methanol denaturing protein. In this study, we used molecular dynamics simulations to investigate how alcohols with varied hydrophobicity and different numbers of hydrophilic groups (hydroxyl groups) exert effects on the structure of the model polypeptide, BBA5. First, we showed that methanol and trifluoroethanol (TFE) but not glycol or glycerol disrupt hydrophobic interactions. The latter two alcohols instead protect the assembly of the α- and β-domains of the polypeptide. Second, all four alcohols were shown to generally increase the stability of secondary structures, as revealed by the increased number of backbone hydrogen bonds formed in alcohol/water solutions compared to that in pure water, although individual hydrogen bonds can be weakened by certain alcohols, such as TFE. The two monohydric alcohols, methanol and TFE, display apparently different sequence-dependence in affecting the backbone hydrogen bond stability: methanol tends to enhance the stability of backbone hydrogen bonds of which the carbonyl groups are from polar residues, whereas TFE tends to stabilize those involving non-polar residues. These results demonstrated that subtle differences in the solution environment could have distinct consequences on protein structures.

  12. 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.

  13. Computational molecular biology approaches to ligand-target interactions

    PubMed Central

    Lupieri, Paola; Nguyen, Chuong Ha Hung; Bafghi, Zhaleh Ghaemi; Giorgetti, Alejandro; Carloni, Paolo

    2009-01-01

    Binding of small molecules to their targets triggers complex pathways. Computational approaches are keys for predictions of the molecular events involved in such cascades. Here we review current efforts at characterizing the molecular determinants in the largest membrane-bound receptor family, the G-protein-coupled receptors (GPCRs). We focus on odorant receptors, which constitute more than half GPCRs. The work presented in this review uncovers structural and energetic aspects of components of the cellular cascade. Finally, a computational approach in the context of radioactive boron-based antitumoral therapies is briefly described. PMID:20119480

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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. PMID:27211924

  1. 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.

  2. 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''.

  3. Molecular Diagnosis of Natural enemy-host Interactions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cryptic behaviors, small size, and rapid movement and feeding actions of arthropod natural enemies dictate the need for alternative technologies for the study of trophic linkages to replace the traditional approaches of direct observation and laboratory experimentation. Many molecular approaches...

  4. The 1992 - 1997 renewal proposal interactive graphics for molecular studies

    NASA Astrophysics Data System (ADS)

    Brooks, Frederick P., Jr.; Wright, William V.

    1991-01-01

    The UNC Resource develops forefront molecular graphics techniques and harnesses them into prototype research tools designed for biochemists studying macromolecules. The end objective is understanding the structure and function of proteins and nucleic acids, crucial to understanding disease and to designing drugs. The Resource is the only molecular graphics group composed chiefly of computer scientists, not chemists. As such, special capabilities and facilities are inherent. Close collaboration is experienced with biochemists and bridges are built between the disciplines. A trailblazer molecular graphics facility is maintained along with a top-performance hardware-software configuration, continually advancing the state of the art and testing the trailblazer against real users. Visiting chemists from everywhere are welcomed and they are helped in the use of the facility. Radical new molecular graphics ideas are generated into the prototype stage. Winning ideas are spun off to the thriving commercial industry or into autonomous research projects. Although commercial products cannot be developed and supported, each prototype is tested on users who come here; then it is distributed to interested users, it is documented, installed, bugs are fixed, and telephone support is provided.

  5. Molecular and ionic diffusion in aqueous - deep eutectic solvent mixtures: probing inter-molecular interactions using PFG NMR.

    PubMed

    D'Agostino, Carmine; Gladden, Lynn F; Mantle, Mick D; Abbott, Andrew P; Ahmed, Essa I; Al-Murshedi, Azhar Y M; Harris, Robert C

    2015-06-21

    Pulsed field gradient (PFG) NMR has been used to probe self-diffusion of molecular and ionic species in aqueous mixtures of choline chloride (ChCl) based deep eutectic solvents (DESs), in order to elucidate the effect of water on motion and inter-molecular interactions between the different species in the mixtures, namely the Ch(+) cation and hydrogen bond donor (HBD). The results reveal an interesting and complex behaviour of such mixtures at a molecular level. In general, it is observed that the hydroxyl protons ((1)H) of Ch(+) and the hydrogen bond donor have diffusion coefficients significantly different from those measured for their parent molecules when water is added. This indicates a clear and significant change in inter-molecular interactions. In aqueous Ethaline, the hydroxyl species of Ch(+) and HBD show a stronger interaction with water as water is added to the system. In the case of Glyceline, water has little effect on both hydroxyl proton diffusion of Ch(+) and HBD. In Reline, it is likely that water allows the formation of small amounts of ammonium hydroxide. The most surprising observation is from the self-diffusion of water, which is considerably higher that expected from a homogeneous liquid. This leads to the conclusion that Reline and Glyceline form mixtures that are inhomogeneous at a microscopic level despite the hydrophilicity of the salt and HBD. This work shows that PFG NMR is a powerful tool to elucidate both molecular dynamics and inter-molecular interactions in complex liquid mixtures, such as the aqueous DES mixtures. PMID:25994171

  6. Revealing the molecular signatures of host-pathogen interactions

    PubMed Central

    2011-01-01

    Advances in sequencing technology and genome-wide association studies are now revealing the complex interactions between hosts and pathogen through genomic variation signatures, which arise from evolutionary co-existence. PMID:22011345

  7. Physical nature of intermolecular interactions inside Sir2 homolog active site: molecular dynamics and ab initio study.

    PubMed

    Czeleń, Przemysław; Czyżnikowska, Żaneta

    2016-06-01

    In the present study, we analyze the interactions of NAD+-dependent deacetylase (Sir2 homolog yeast Hst2) with carba-nicotinamide-adenine-dinucleotide (ADP-HPD). For the Sir2 homolog, a yeast Hst2 docking procedure was applied. The structure of the protein-ADP-HPD complex obtained during the docking procedure was used as a starting point for molecular dynamics simulation. The intermolecular interaction energy partitioning was performed for protein-ADP-HPD complex resulting from molecular dynamics simulation. The analysis was performed for ADP-HPD and 15 amino acids forming a deacetylase binding pocket. Although the results indicate that the first-order electrostatic interaction energy is substantial, the presence of multiple hydrogen bonds in investigated complexes can lead to significant value of induction component. PMID:27154340

  8. Hydrolysable ATP is a requirement for the correct interaction of molecular chaperonins cpn60 and cpn10.

    PubMed Central

    Walters, Chris; Errington, Neil; Rowe, Arther J; Harding, Stephen E

    2002-01-01

    Over recent years the binding ability of the molecular chaperone cpn60 (GroEL14) and its co-chaperone cpn10 (GroES7) has been reported to occur under an assortment of specific conditions from the use of non-hydrolysable ATP analogues (namely adenosine 5'-[gamma-thio]triphosphate) to requiring hydrolysable ATP for any interaction to occur. We have investigated this further using the molecular hydrodynamic methods (hydrodynamic bead modelling, sedimentation-velocity analytical ultracentrifugation and dynamic light-scattering), allowing the process to be followed under physiologically relevant dilute solution conditions, combined with absorption spectrophotometry to determine GroES7-GroEL14 interaction through the rate inhibition of the cpn60's ATPase activity by GroES7. The results found here indicate that the presence of hydrolysable ATP is required to facilitate correct GroES7 interaction with GroEL14 in solution. PMID:12049650

  9. A molecular dynamics investigation of surface reconstruction on magnetite (001)

    NASA Astrophysics Data System (ADS)

    Rustad, J. R.; Wasserman, E.; Felmy, A. R.

    1999-07-01

    Molecular dynamics calculations using analytical potential functions with polarizable oxygen ions have been used to identify a novel mode of reconstruction on the half-occupied tetrahedral layer termination of the magnetite (Fe 3O 4) (001) surface. In the proposed reconstruction, the twofold coordinated iron ion in the top monolayer rotates downward to occupy a vacant half-octahedral site in the plane of the second-layer iron ions. At the same time, half of the tetrahedral iron ions in the third iron layer are pushed upward to occupy an adjacent octahedral vacancy at the level of the second-layer iron ions. The other half of the third-layer iron ions remain roughly in their original positions. The proposed reconstruction is consistent with recent low-energy electron diffraction and X-ray photoelectron spectroscopy results. It also provides a compelling interpretation for the arrangement of atoms suggested by high-resolution scanning-tunneling microscopy studies.

  10. 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

  11. Alternative Radioligands for Investigating the Molecular Pharmacology of Melatonin Receptors.

    PubMed

    Legros, Céline; Brasseur, Chantal; Delagrange, Philippe; Ducrot, Pierre; Nosjean, Olivier; Boutin, Jean A

    2016-03-01

    Melatonin exerts a variety of physiologic activities that are mainly relayed through the melatonin receptors MT1 and MT2 Low expressions of these receptors in tissues have led to widespread experimental use of the agonist 2-[(125)I]-iodomelatonin as a substitute for melatonin. We describe three iodinated ligands: 2-(2-[(2-iodo-4,5-dimethoxyphenyl)methyl]-4,5-dimethoxy phenyl) (DIV880) and (2-iodo-N-2-[5-methoxy-2-(naphthalen-1-yl)-1H-pyrrolo[3,2-b]pyridine-3-yl])acetamide (S70254), which are specific ligands at MT2 receptors, and N-[2-(5-methoxy-1H-indol-3-yl)ethyl]iodoacetamide (SD6), an analog of 2-[(125)I]-iodomelatonin with slightly different characteristics. Here, we further characterized these new ligands with regards to their molecular pharmacology. We performed binding experiments, saturation assays, association/dissociation rate measurements, and autoradiography using sheep and rat tissues and recombinant cell lines. Our results showed that [(125)I]-S70254 is receptor, and can be used with both cells and tissue. This radioligand can be used in autoradiography. Similarly, DIV880, a partial agonist [43% of melatonin on guanosine 5'-3-O-(thio)triphosphate binding assay], selective for MT2, can be used as a tool to selectively describe the pharmacology of this receptor in tissue samples. The molecular pharmacology of both human melatonin receptors MT1 and MT2, using a series of 24 ligands at these receptors and the new radioligands, did not lead to noticeable variations in the profiles. For the first time, we described radiolabeled tools that are specific for one of the melatonin receptors (MT2). These tools are amenable to binding experiments and to autoradiography using sheep or rat tissues. These specific tools will permit better understanding of the role and implication in physiopathologic processes of the melatonin receptors. PMID:26759496

  12. 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

  13. Investigation of soil-atmosphere interaction in pyroclastic soils

    NASA Astrophysics Data System (ADS)

    Rianna, Guido; Pagano, Luca; Urciuoli, Gianfranco

    2014-03-01

    This paper investigates the interaction between soil and atmosphere in pyroclastic soils with a view to understanding whether and to what extent the prediction of the hydraulic (and mechanical) behaviour of geotechnical problems (cuts, slope stabilities, embankments, foundation, retaining structures) regulated by rainfall-induced fluctuations of matric suction is influenced by evaporation phenomena. Evaporation fluxes are quantified and compared with other fluxes (precipitation, run-off, deep drainage) affecting soil water content and matric suction. This work is based on the data collected through a physical model over 2 years of experimental tests. The model consisted of a 1 m3 tank, filled in this case with pyroclastic soil and exposed to natural weather elements. The system was extensively monitored to record atmospheric and soil variables. The results provided by the experiments highlight the importance of the top-soil state in determining the intensities of infiltrating rainfall and actual evaporation. The results also bring to light the significance of evaporation which, during the dry season, largely prevails over infiltration, raising suction to very high values. Also during the wet season, evaporation gives rise to a non-negligible flux with respect to the infiltrated precipitation. The reliability of two pre-existing empirical models to estimate evaporation flux is also investigated and appraised within this paper.

  14. The investigation of solid-solid phase transformation at CuAlNi alloy using molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Kazanc, Sefa; Ahmet Celik, Fatih; Ozgen, Soner

    2013-12-01

    In this study the thermodynamic and structural properties of a CuAlNi model alloy (3A) system were investigated using a molecular dynamics (MD) simulation method. The interactions between atoms were modelled by the Sutton-Chen embedded atom method (SCEAM) based on many-body interactions. It was observed that at the end of thermal process the thermo-elastic phase transformation occurred in the model alloy system. In order to analyse the structures obtained from MD simulation, techniques such as thermodynamic parameters and radial distribution function (RDF) were used. The local atomic order in the model alloy was analysed using Honeycutt-Andersen (HA) method.

  15. A co-axially configured submillimeter spectrometer and investigations of hydrogen bound molecular complexes

    NASA Astrophysics Data System (ADS)

    McElmurry, Blake Anthony

    The development of a co-axially configured submillimeter spectrometer is reported. The spectrometer has been constructed to observe molecular complexes that exhibit non-covalent interactions with energies much less than that of a traditional covalent bond. The structure of molecular complexes such as those formed between a rare gas and a hydrogen halide, Rg:HX where Rg is a rare gas (Rg=Ne, Ar and Kr) and HX (X=F, Cl, Br and I) can be determined directly and accurately. The center of mass interaction distance, RCM, as well as the angle of the hydrogen halide is determined, along with direct evaluation of the intermolecular vibrations as well as accurate isomerization energies between the hydrogen bound and van der Waals forms. The accuracy of the frequency determination of rovibrational transitions using the submillimeter spectrometer is also evaluated by direct comparison with the state-of-the-art pulsed nozzle Fourier transform microwave spectrometer, and this accuracy is estimated to be less than 1 kHz at 300 GHz. The tunneling or geared bending vibration of a dimer of hydrogen bromide or hydrogen iodide has been investigated. The selection rules, nuclear statistics and intensity alternation for transitions observed in these dimmers, which is a consequence of interchanging two identical nuclei in the low frequency geared bending vibration of the molecular complex, are reported. Furthermore, the rotation and quadrupole coupling constants are used to determine a vibrationally averaged structure of the complex. The energy of the low frequency bending vibration can then be compared with ab initio based potential energy surfaces. A study of the multiple isomeric forms of the molecular complex OC:HI is also presented. Multiple isotopic substitutions are used to determine the relevant ground state structures and data reported evidence for an anomalous isotope effect supporting a ground state isotopic isomerization effect. All spectroscopic data that has been reported

  16. 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. PMID:26595382

  17. 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

  18. 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

  19. 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. PMID:26657340

  20. 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

  1. 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

  2. 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)

  3. CF interaction with Si(1 0 0)-(2 × 1): Molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Gou, F.; Gleeson, M. A.; Kleyn, A. W.

    2007-01-01

    In this study, the interaction of CF with the clean Si(1 0 0)-(2 × 1) surface at normal incidence and room temperature was investigated using molecular dynamics simulation. Incident energies of 2, 12 and 50 eV were simulated. C atoms, arising from dissociation, preferentially react with Si to form Si-C bonds. A Si xC yF z interfacial layer is formed, but no etching is observed. The interfacial layer thickness increases with increasing incident energy, mainly through enhanced penetration of the silicon lattice. Silicon carbide and fluorosilyl species are formed at 50 eV, which is in good agreement with available experimental data. The level of agreement between the simulated and experimental results is discussed.

  4. Molecular simulation of protein-surface interactions: Benefits, problems, solutions, and future directions (Review)

    PubMed Central

    Latour, Robert A.

    2009-01-01

    While the importance of protein adsorption to materials surfaces is widely recognized, little is understood at this time regarding how to design surfaces to control protein adsorption behavior. All-atom empirical force field molecular simulation methods have enormous potential to address this problem by providing an approach to directly investigate the adsorption behavior of peptides and proteins at the atomic level. As with any type of technology, however, these methods must be appropriately developed and applied if they are to provide realistic and useful results. Three issues that are particularly important for the accurate simulation of protein adsorption behavior are the selection of a valid force field to represent the atomic-level interactions involved, the accurate representation of solvation effects, and system sampling. In this article, each of these areas is addressed and future directions for continued development are presented. PMID:19809597

  5. 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

  6. Effect of substituent pattern and molecular weight of cellulose ethers on interactions with different bile salts.

    PubMed

    Torcello-Gómez, Amelia; Fernández Fraguas, Cristina; Ridout, Mike J; Woodward, Nicola C; Wilde, Peter J; Foster, Timothy J

    2015-03-01

    Some known mechanisms proposed for the reduction of blood cholesterol by dietary fibre are: binding with bile salts in the duodenum and prevention of lipid absorption, which can be partially related with the bile salt binding. In order to gain new insights into the mechanisms of the binding of dietary fibre to bile salts, the goal of this work is to study the main interactions between cellulose derivatives and two types of bile salts. Commercial cellulose ethers: methyl (MC), hydroxypropyl (HPC) and hydroxypropylmethyl cellulose (HPMC), have been chosen as dietary fibre due to their highly functional properties important in manufactured food products. Two types of bile salts: sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC), have been chosen to understand the effect of the bile salt type. Interactions in the bulk have been investigated by means of differential scanning calorimetry (DSC) and linear mechanical spectroscopy. Results show that both bile salts have inhibitory effects on the thermal structuring of cellulose ethers and this depends on the number and type of substitution in the derivatised celluloses, and is not dependent upon molecular weight. Concerning the bile salt type, the more hydrophobic bile salt (NaTDC) has greater effect on these interactions, suggesting more efficient adsorption onto cellulose ethers. These findings may have implications in the digestion of cellulose-stabilised food matrices, providing a springboard to develop new healthy cellulose-based food products with improved functional properties. PMID:25679293

  7. 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

  8. 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

  9. 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

  10. Molecular interactions of dimethyl methylphosphonate (DMMP) with metalloporphyrins: Determination of the binding mechanism by spectroscopic methods

    NASA Astrophysics Data System (ADS)

    Zhang, Suyi; Yang, Limin; Huo, Danqun; Liu, Xiaojuan; Li, Juan; Fa, Huanbao; Zhang, Liang; Hou, Changjun

    2012-03-01

    The molecular interactions of 5,10,15,20-tetraphenylporphine zinc (ZnTPP) and 5,10,15,20-tetraphenyl-21H,23H-porphine cobalt(II) (CoTPP) with dimethyl methylphosphonate (DMMP) have been investigated by absorption/absorption difference spectroscopy. The interactions between the metalloporphyrins and DMMP change the absorbance characteristics of the porphyrins resulted from the formation of the metalloporphyrin-DMMP complexes. According to the Benesi-Hildebrand (B-H) equation, the equilibrium constants and stoichiometries of the binding systems at four different temperatures (288, 293, 298 and 303 K) were obtained. Experimental results showed that both ZnTPP and CoTPP bind to DMMP via axial coordination, resulting in the formation of 1:1 metalloporphyrin-DMMP complexes. However, it was found that ZnTPP showed stronger binding capacity with the equilibrium constant (K) of 83.864 M-1 at room temperature, while CoTPP exhibited weaker binding with K of 24.904 M-1. The thermodynamic parameters, enthalpy change (ΔHmθ), entropy change (ΔSmθ) and free energy changes (ΔGmθ) were also studied for the interactions, indicating that the formation of the metalloporphyrins-DMMP complex was an exothermic reaction.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. Molecular modeling of Al 3+ and benzene interactions with Suwannee fulvic acid

    NASA Astrophysics Data System (ADS)

    Trout, Chad C.; Kubicki, James D.

    2007-08-01

    The effects that Al 3+ and benzene interactions exhibit on a model fulvic acid were investigated. Energy minimizations of the structures mimicking the interactions of Al 3+-Suwannee fulvic acid (SFA), benzene-SFA and Al 3+-benzene-SFA were run with a solvation sphere of 60 H 2O molecules with the semi-empirical methods PM3 and PM5. The semi-empirical method PM3 was run with Gaussian 98 and CAChe Workstation Pro 6.1.1 to compare the results of the energy minimization algorithms in the two programs. PM5 calculations were run with CAChe Workstation Pro 6.1.1. Molecular dynamics (MD) simulations were run in Cerius 2 (Accelrys Inc., San Diego, CA) using the Universal Force Field (UFF) 1.02 [Rappé A. K., Casewit C., Colwell K., Goddard W., and Skiff W. (1992) UFF, a full periodic-table force-field for molecular mechanics and molecular dynamics simulations. J. Am. Chem. Soc.114(25), 10024-10035] and COMPASS force field [Sun H. (1998) COMPASS: an ab initio force-field optimized for condensed-phase applications—overview with details on alkane and benzene compounds. J. Phys. Chem. B102, 7338-7364]. Single point calculations were run on the minimized structures at the B3LYP/6-31G(d) level to obtain more accurate estimates of the energy on the minimized structures derived from the PM3, PM5, and UFF methods and to normalize energies to the same reference state. This methodology was used as the standard of comparison for all the models to assess whether or not a given configuration was reasonably stable. The PM3/G03 energy minimizations predicted the lowest B3LYP/6-31G(d) potential energies of the methodologies examined in this study. Thus, this method is considered the most reliable of those tested. The PM3/G03 method predicted that there would be aromatic-aromatic interactions between benzene and SFA. The presence of Al 3+ was predicted not to interfere with aromatic-aromatic interactions between benzene and SFA, but benzene may influence the location of metal complexation

  16. Challenges for automatically extracting molecular interactions from full-text articles

    PubMed Central

    McIntosh, Tara; Curran, James R

    2009-01-01

    Background The increasing availability of full-text biomedical articles will allow more biomedical knowledge to be extracted automatically with greater reliability. However, most Information Retrieval (IR) and Extraction (IE) tools currently process only abstracts. The lack of corpora has limited the development of tools that are capable of exploiting the knowledge in full-text articles. As a result, there has been little investigation into the advantages of full-text document structure, and the challenges developers will face in processing full-text articles. Results We manually annotated passages from full-text articles that describe interactions summarised in a Molecular Interaction Map (MIM). Our corpus tracks the process of identifying facts to form the MIM summaries and captures any factual dependencies that must be resolved to extract the fact completely. For example, a fact in the results section may require a synonym defined in the introduction. The passages are also annotated with negated and coreference expressions that must be resolved. We describe the guidelines for identifying relevant passages and possible dependencies. The corpus includes 2162 sentences from 78 full-text articles. Our corpus analysis demonstrates the necessity of full-text processing; identifies the article sections where interactions are most commonly stated; and quantifies the proportion of interaction statements requiring coherent dependencies. Further, it allows us to report on the relative importance of identifying synonyms and resolving negated expressions. We also experiment with an oracle sentence retrieval system using the corpus as a gold-standard evaluation set. Conclusion We introduce the MIM corpus, a unique resource that maps interaction facts in a MIM to annotated passages within full-text articles. It is an invaluable case study providing guidance to developers of biomedical IR and IE systems, and can be used as a gold-standard evaluation set for full-text IR tasks

  17. New insights into the molecular mechanisms of biomembrane structural changes and interactions by optical biosensor technology.

    PubMed

    Lee, Tzong-Hsien; Hirst, Daniel J; Aguilar, Marie-Isabel

    2015-09-01

    Biomolecular-membrane interactions play a critical role in the regulation of many important biological processes such as protein trafficking, cellular signalling and ion channel formation. Peptide/protein-membrane interactions can also destabilise and damage the membrane which can lead to cell death. Characterisation of the molecular details of these binding-mediated membrane destabilisation processes is therefore central to understanding cellular events such as antimicrobial action, membrane-mediated amyloid aggregation, and apoptotic protein induced mitochondrial membrane permeabilisation. Optical biosensors have provided a unique approach to characterising membrane interactions allowing quantitation of binding events and new insight into the kinetic mechanism of these interactions. One of the most commonly used optical biosensor technologies is surface plasmon resonance (SPR) and there have been an increasing number of studies reporting the use of this technique for investigating biophysical analysis of membrane-mediated events. More recently, a number of new optical biosensors based on waveguide techniques have been developed, allowing membrane structure changes to be measured simultaneously with mass binding measurements. These techniques include dual polarisation interferometry (DPI), plasmon waveguide resonance spectroscopy (PWR) and optical waveguide light mode spectroscopy (OWLS). These techniques have expanded the application of optical biosensors to allow the analysis of membrane structure changes during peptide and protein binding. This review provides a theoretical and practical overview of the application of biosensor technology with a specific focus on DPI, PWR and OWLS to study biomembrane-mediated events and the mechanism of biomembrane disruption. This article is part of a Special Issue entitled: Lipid-protein interactions. PMID:26009270

  18. 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.

  19. 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.

  20. Molecular interactions between gold nanoparticles and model cell membranes.

    PubMed

    Hu, Peipei; Zhang, Xiaoxian; Zhang, Chi; Chen, Zhan

    2015-04-21

    The interactions between nanoparticles (NPs) and cells are of huge interest because NPs have been extensively researched for biomedical applications. For the cellular entry of NPs, it remains unclear how the cell membrane molecules respond to the exposure of NPs due to a lack of appropriate surface/interface-sensitive techniques to study NP-cell membrane interactions in situ in real time. In this study, sum frequency generation (SFG) vibrational spectroscopy was employed to examine the interactions between lipid bilayers (serving as model mammalian cell membranes) and Au NPs of four different sizes with the same mass, or the same NP number, or the same NP surface area. It was found that lipid flip-flop was induced by Au NPs of all four sizes. Interestingly, the lipid flip-flop rate was found to increase as the Au NP size increased with respect to the same particle number or the same NP surface area. However, the induced lipid flip-flop rate was the same for Au NPs with different sizes with the same mass, which was interpreted by the same "effective surface contact area" between Au NPs and the model cell membrane. We believe that this study provided the first direct observation of the lipid flip-flop induced by the interactions between Au NPs and the model mammalian cell membrane. PMID:25776800

  1. Molecular and immunodiagnostic investigations on bovine neosporosis in Switzerland.

    PubMed

    Gottstein, B; Hentrich, B; Wyss, R; Thür, B; Busato, A; Stärk, K D; Müller, N

    1998-04-01

    Neospora caninum has gained considerable attention through its role in the aetiology of bovine abortion. Due to its close phylogenetic relationship with Toxoplasma gondii, respective unequivocal differential diagnosis deserves special consideration. In order to evaluate the diagnostic performance of molecular and immunodiagnostic techniques and to provide insights into the epidemiological significance of bovine neosporosis in Switzerland, we conducted a study on 83 cases of bovine abortion: of these, 24 (29%) foetal brains were positive by Neospora-PCR, six of these foetuses were simultaneously seropositive in Neospora-IFAT and/or somatic antigen-ELISA. Conversely, four (5%) foetal brains were considered positive by Toxoplasma-PCR, two of which were also seropositive in the Toxoplasma-P30-ELISA and/or direct agglutination test. The seroprevalence in 1689 cattle sera obtained from 113 diary farms was 11.5% (95% confidence interval: 9.2-13.8) by Neospora-somatic antigen-ELISA were and 10.7% (95% confidence interval: 8.3-12.6) by Toxoplasma-P30-ELISA. From the same samples, 1.1%, less than statistically expected, were positive in both ELISA. Within selected groups of cow-calf farms, the seroprevalence determined using the Neospora-somatic antigen-ELISA was 14% (95% confidence interval 5.0-23.0) for dams and 15% (95% confidence interval: 3.0-28.0) for offspring calves. Seroprevalences determined by Toxoplasma-P30-ELISA were 8% (95% confidence interval: 4.0-12.0) for dams and 3% (95% confidence interval: 0.3-6.0) for calves. None of the sera gave a positive reaction in both ELISA. Our data indicated that prenatal neosporosis appears as an important cause of bovine abortion in Switzerland. PMID:9602392

  2. Molecular dynamics investigations of PRODAN in a DLPC bilayer.

    PubMed

    Nitschke, William K; Vequi-Suplicy, Cíntia C; Coutinho, Kaline; Stassen, Hubert

    2012-03-01

    Molecular dynamics computer simulations have been performed to identify preferred positions of the fluorescent probe PRODAN in a fully hydrated DLPC bilayer in the fluid phase. In addition to the intramolecular charge-transfer first vertical excited state, we considered different charge distributions for the electronic ground state of the PRODAN molecule by distinct atomic charge models corresponding to the probe molecule in vacuum as well as polarized in a weak and a strong dielectric solvent (cyclohexane and water). Independent on the charge distribution model of PRODAN, we observed a preferential orientation of this molecule in the bilayer with the dimethylamino group pointing toward the membrane's center and the carbonyl oxygen toward the membrane's interface. However, changing the charge distribution model of PRODAN, independent of its initial position in the equilibrated DLPC membrane, we observed different preferential positions. For the ground state representation without polarization and the in-cyclohexane polarization, the probe maintains its position close to the membrane's center. Considering the in-water polarization model, the probe approaches more of the polar headgroup region of the bilayer, with a strong structural correlation with the choline group, exposing its oxygen atom to water molecules. PRODAN's representation of the first vertical excited state with the in-water polarization also approaches the polar region of the membrane with the oxygen atom exposed to the bilayer's hydration shell. However, this model presents a stronger structural correlation with the phosphate groups than the ground state. Therefore, we conclude that the orientation of the PRODAN molecule inside the DLPC membrane is well-defined, but its position is very sensitive to the effect of the medium polarization included here by different models for the atomic charge distribution of the probe. PMID:22329741

  3. 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

  4. Diagnostic utility of molecular investigation in extraskeletal myxoid chondrosarcoma.

    PubMed

    Benini, Stefania; Cocchi, Stefania; Gamberi, Gabriella; Magagnoli, Giovanna; Vogel, Daniela; Ghinelli, Cristina; Righi, Alberto; Picci, Piero; Alberghini, Marco; Gambarotti, Marco

    2014-05-01

    Extraskeletal myxoid chondrosarcoma is characterized by the reciprocal chromosomal translocation t(9;22) and the resultant fused gene EWS RNA-binding protein 1 and nuclear receptor subfamily 4, group A, member 3 (EWSR1-NR4A3). A second cytogenetic rearrangement t(9;17) involves the genes NR4A3 and TAF 15 RNA polymerase II, TATA box binding protein (TBP)-associated factor (TAF15). Less frequent fusion transcript variants of the NR4A3 gene, transcription factor 12 (TCF12)-NR4A3 and TRK-fused gene (TFG)-NR4A3, are associated with t(9;15) and t(9;3) respectively. The samples from 42 patients with extraskeletal myxoid chondrosarcoma were examined for the presence of EWSR1-NR4A3, TAF15-NR4A3, TCF12-NR4A3, and TFG-NR4A3 fusion transcripts by using RT-PCR. Fluorescence in situ hybridization was performed to analyze the status of EWSR1 and NR4A3 genes. The fusion transcripts were detected in 34 of 42 samples (81%); the presence of an EWSR1 or NR4A3 gene rearrangements were detected in 8 of 42 samples (19%) which had tested negative for all fusion transcripts detected by RT-PCR. Of the 34 samples evaluable for fusion transcripts, 23 yielded positive results for EWSR1-NR4A3, 10 for TAF15-NR4A3, and 1 for TCF12-NR4A3. The combination of RT-PCR and fluorescence in situ hybridization on frozen and paraffin-embedded tissue is a sensitive and specific method for molecular detection of recurrent translocations and is an important ancillary method to establish the diagnosis of extraskeletal myxoid chondrosarcoma. PMID:24508382

  5. Calsyntenin-3 Molecular Architecture and Interaction with Neurexin 1α*

    PubMed Central

    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

    2014-01-01

    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 Ca2+, 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 Ca2+ 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. PMID:25352602

  6. Key Inter-molecular Interactions in the E. Coli 70S Ribosome Revealed by Coarse-Grained Analysis

    PubMed Central

    Zhang, Zhiyong; Sanbonmatsu, Karissa Y.; Voth, Gregory A.

    2011-01-01

    The ribosome is a very large complex, which consists of many RNA and protein molecules and plays a central role in protein biosynthesis in all organisms. Extensive interactions between different molecules are critical to ribosomal functional dynamics. In this work, inter-molecular interactions in the E. coli 70S ribosome are investigated by coarse-grained (CG) analysis. CG models are defined to preserve dynamic domains in RNAs and proteins, and capture functional motions in the ribosome, then the CG sites are connected by harmonic springs and spring constants are obtained by matching the computed fluctuations to those of an all-atom molecular dynamics (MD) simulation. Those spring constants indicate how strong the interactions are between the ribosomal components, which are in good agreement with various experimental data. Nearly all of bridges between the small and large ribosomal subunits are indicated by CG interactions with large spring constants. The head of the small subunit is very mobile because it has the minimal CG interactions with the rest of the subunit; However, a large number of small subunit proteins bind to maintain the internal structure of the head. The results show a clear connection between the inter-molecular interactions and the structural and functional properties of the ribosome because of the reduced complexity in domain-based CG models. The present approach also provides a useful strategy to map interactions between molecules within large biomolecular complexes since it is not straightforward to investigate these by either atomistic MD simulations or residue-based elastic network models. PMID:21910449

  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. PMID:21665198

  8. Investigation of SOL plasma interaction with graphite PFC

    NASA Astrophysics Data System (ADS)

    Lim, Sun-Taek; Kim, Hyun-Su; Jin, Younggil; Lee, Jin Young; Song, Jae-Min; Kim, Gon-Ho

    2015-08-01

    Morphological changes of graphite plasma facing component (PFC) were investigated with various ion irradiation conditions which may change the sputtering yield and the scrape-off layer (SOL) plasma property. The experiments were carried out by using electron cyclotron resonance deuterium plasma with the conditions of electron density range of 2.5-3.5 × 1011 cm-3, electron temperature range of 3.3-4.1 eV, and ion energy range of 17-100 eV. The graphite morphology was changed from plane to conical tip with increasing ion energy and dose. In addition, morphological changes increase the sputtering yield due to the increase of local angle of ion incidence. The inflow of hydrocarbon causes the increase of electron density and the decrease of electron temperature due to its higher dissociation and ionization rates than those of deuterium. This result suggests that the morphological changes of graphite should be considered in the SOL plasma interaction with graphite PFC.

  9. Investigation of plasma particle interactions with variable particle sizes

    NASA Astrophysics Data System (ADS)

    Dropmann, Michael; Laufer, Rene; Herdrich, Georg; Matthews, Lorin; Hyde, Truell

    2015-11-01

    In dusty plasmas, the dust particles are subjected to many forces of different origins. Both the gas and plasma directly affect the dust particles through electric fields, neutral drag, ion drag and thermophoretic forces, while the particles themselves interact with one another through a screened coulomb potential, which can be influenced by flowing ions. Recently, micron sized particles have been used as probes to analyze the electric fields in the plasma directly. A proper analysis of the resulting data requires a full understanding of the manner in which these forces couple to the dust particles. In most cases each of the forces exhibit unique characteristics, many of which are partially dependent on the particle size. In this study, five different particle sizes are used to investigate the forces resident in the sheath above the lower electrode of a GEC RF reference cell. The particles are tracked using a high-speed camera, yielding two-dimensional force maps allowing the force on the particles to be described as a polynomial series. It will be shown that the data collected can be analyzed to reveal information about the origins of the various forces. Support from the NSF and the DOE (award numbers PHY-1262031 and PHY-1414523) is gratefully acknowledged.

  10. Investigation of helicopter rotor blade/wake interactive impulsive noise

    NASA Technical Reports Server (NTRS)

    Miley, S. J.; Hall, G. F.; Vonlavante, E.

    1987-01-01

    An analysis of the Tip Aerodynamic/Aeroacoustic Test (TAAT) data was performed to identify possible aerodynamic sources of blade/vortex interaction (BVI) impulsive noise. The identification is based on correlation of measured blade pressure time histories with predicted blade/vortex intersections for the flight condition(s) where impulsive noise was detected. Due to the location of the recording microphones, only noise signatures associated with the advancing blade were available, and the analysis was accordingly restricted to the first and second azimuthal quadrants. The results show that the blade tip region is operating transonically in the azimuthal range where previous BVI experiments indicated the impulsive noise to be. No individual blade/vortex encounter is identifiable in the pressure data; however, there is indication of multiple intersections in the roll-up region which could be the origin of the noise. Discrete blade/vortex encounters are indicated in the second quadrant; however, if impulsive noise were produced here, the directivity pattern would be such that it was not recorded by the microphones. It is demonstrated that the TAAT data base is a valuable resource in the investigation of rotor aerodynamic/aeroacoustic behavior.

  11. Theoretical investigation of the halogen bonded complexes between carbonyl bases and molecular chlorine.

    PubMed

    Zierkiewicz, Wiktor; Bieńko, Dariusz C; Michalska, Danuta; Zeegers-Huyskens, Thérèse

    2015-04-30

    The halogen bonded complexes between six carbonyl bases and molecular chlorine are investigated theoretically. The interaction energies calculated at the CCSD(T)/aug-cc-pVTZ level range between -1.61 and -3.50 kcal mol(-1). These energies are related to the ionization potential, proton affinity, and also to the most negative values (V(s,min)) on the electrostatic potential surface of the carbonyl bases. A symmetry adapted perturbation theory decomposition of the energies has been performed. The interaction results in an elongation of the Cl-Cl bond and a contraction of the CF and CH bonds accompanied by a blue shift of the ν(CH) vibrations. The properties of the Cl2 molecules are discussed as a function of the σ*(Cl-Cl) occupation, the hybridization, and the occupation of the Rydberg orbitals of the two chlorine atoms. Our calculations predict a large enhancement of the infrared and Raman intensities of the ν(Cl-Cl) vibration on going from isolated to complexed Cl2. PMID:25727322

  12. Epitaxial interactions between molecular overlayers and ordered substrates

    NASA Astrophysics Data System (ADS)

    Hillier, Andrew C.; Ward, Michael D.

    1996-11-01

    A framework for evaluating the epitaxy of crystalline organic overlayers of generic symmetry on ordered substrates is described, which combines a computationally efficient analytical method for explicit determination of the type of epitaxy (i.e., commensurism, coincidence, or incommensurism) and overlayer azimuthal orientation with an analysis of the elastic properties of the overlayer and the overlayer-substrate interface. The azimuthal orientations predicted by the analytical method agree with values predicted by semiempirical potential-energy calculations and observed experimentally for previously reported organic overlayers which are demonstrated here to be coincident. Calculations based on this analytical approach are much less computationally intensive than potential-energy calculations, as the number of computational operations is independent of the overlayer size chosen for analysis. This enables analyses to be performed for the large overlayer basis sets common for molecular overlayers. Furthermore, this facilitates the analysis of coincident overlayers, for which the overlayer size needs to be large enough to establish a phasing relationship between a substrate and a large nonprimitive overlayer supercell so that the global minimum with respect to azimuthal angle can be determined. The computational efficiency of this method also enables a convenient examination of numerous possible reconstructed overlayer configurations in which the lattice parameters are bracketed around those of the native overlayer, thereby allowing examination of possible epitaxy-driven overlayer reconstructions. When combined with calculated intralayer- and overlayer-substrate elastic constants, this method provides a strategy for the design of heteroepitaxial molecular films.

  13. 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.

  14. 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…

  15. Photolytic Labeling to Probe Molecular Interactions in Lyophilized Powders

    PubMed Central

    Iyer, Lavanya K.; Moorthy, Balakrishnan S.; Topp, Elizabeth M.

    2014-01-01

    Local side-chain interactions in lyophilized protein formulations were mapped using solid-state photolytic labeling-mass spectrometry (ssPL-MS). Photoactive amino acid analogs (PAAs) were used as probes and either added to the lyophilized matrix or incorporated within the amino acid sequence of a peptide. In the first approach, apomyoglobin was lyophilized with sucrose and varying concentrations of photo-leucine (L-2-amino-4, 4′-azipentanoic acid; pLeu). The lyophilized solid was irradiated at 365 nm to initiate photolabeling. The rate and extent of labeling were measured using ESI-HPLC-MS, with labeling reaching a plateau at ∼ 30 min, forming up to 6 labeled populations. Bottom-up MS/MS analysis was able to provide peptidelevel resolution of the location of pLeu. ssPL-MS was also able to detect differences in side-chain environment between sucrose and guanidine hydrochloride formulations. In the second approach, peptide GCG (1-8)* containing p-benzoyl-L-phenylalanine (pBpA) in the amino acid sequence was lyophilized with various excipients and irradiated. Peptide-peptide and peptide-excipient adducts were detected using MS. Top-down MS/MS on the peptide dimer provided amino acidlevel resolution regarding interactions and the cross-linking partner for pBpA in the solid state. The results show that ssPL-MS can provide high-resolution information about protein interactions in the lyophilized environment. PMID:24125175

  16. Molecular architecture of the Dam1 complex–microtubule interaction

    PubMed Central

    Legal, Thibault; Zou, Juan; Sochaj, Alicja; Rappsilber, Juri

    2016-01-01

    Mitosis is a highly regulated process that allows the equal distribution of the genetic material to the daughter cells. Chromosome segregation requires the formation of a bipolar mitotic spindle and assembly of a multi-protein structure termed the kinetochore to mediate attachments between condensed chromosomes and spindle microtubules. In budding yeast, a single microtubule attaches to each kinetochore, necessitating robustness and processivity of this kinetochore–microtubule attachment. The yeast kinetochore-localized Dam1 complex forms a direct interaction with the spindle microtubule. In vitro, the Dam1 complex assembles as a ring around microtubules and couples microtubule depolymerization with cargo movement. However, the subunit organization within the Dam1 complex, its higher-order oligomerization and how it interacts with microtubules remain under debate. Here, we used chemical cross-linking and mass spectrometry to define the architecture and subunit organization of the Dam1 complex. This work reveals that both the C termini of Duo1 and Dam1 subunits interact with the microtubule and are critical for microtubule binding of the Dam1 complex, placing Duo1 and Dam1 on the inside of the ring structure. Integrating this information with available structural data, we provide a coherent model for how the Dam1 complex self-assembles around microtubules. PMID:26962051

  17. The HUPO PSI's molecular interaction format--a community standard for the representation of protein interaction data.

    PubMed

    Hermjakob, Henning; Montecchi-Palazzi, Luisa; Bader, Gary; Wojcik, Jérôme; Salwinski, Lukasz; Ceol, Arnaud; Moore, Susan; Orchard, Sandra; Sarkans, Ugis; von Mering, Christian; Roechert, Bernd; Poux, Sylvain; Jung, Eva; Mersch, Henning; Kersey, Paul; Lappe, Michael; Li, Yixue; Zeng, Rong; Rana, Debashis; Nikolski, Macha; Husi, Holger; Brun, Christine; Shanker, K; Grant, Seth G N; Sander, Chris; Bork, Peer; Zhu, Weimin; Pandey, Akhilesh; Brazma, Alvis; Jacq, Bernard; Vidal, Marc; Sherman, David; Legrain, Pierre; Cesareni, Gianni; Xenarios, Ioannis; Eisenberg, David; Steipe, Boris; Hogue, Chris; Apweiler, Rolf

    2004-02-01

    A major goal of proteomics is the complete description of the protein interaction network underlying cell physiology. A large number of small scale and, more recently, large-scale experiments have contributed to expanding our understanding of the nature of the interaction network. However, the necessary data integration across experiments is currently hampered by the fragmentation of publicly available protein interaction data, which exists in different formats in databases, on authors' websites or sometimes only in print publications. Here, we propose a community standard data model for the representation and exchange of protein interaction data. This data model has been jointly developed by members of the Proteomics Standards Initiative (PSI), a work group of the Human Proteome Organization (HUPO), and is supported by major protein interaction data providers, in particular the Biomolecular Interaction Network Database (BIND), Cellzome (Heidelberg, Germany), the Database of Interacting Proteins (DIP), Dana Farber Cancer Institute (Boston, MA, USA), the Human Protein Reference Database (HPRD), Hybrigenics (Paris, France), the European Bioinformatics Institute's (EMBL-EBI, Hinxton, UK) IntAct, the Molecular Interactions (MINT, Rome, Italy) database, the Protein-Protein Interaction Database (PPID, Edinburgh, UK) and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING, EMBL, Heidelberg, Germany). PMID:14755292

  18. Investigation of interaction of nuclear fast red with human serum albumin by experimental and computational approaches.

    PubMed

    Gholivand, Mohammad-Bagher; Jalalvand, Ali R; Goicoechea, Hector C; Omidi, Mehdi

    2013-11-01

    For the first time, interaction of nuclear fast red (NFR) with human serum albumin (HSA) was studied by experimental and computational approaches. Firstly, experimental measurements including fluorescence spectroscopy (F), UVvis spectrophotometry (UVvis), cyclic voltammetry (CV), differential pulse voltammetry (DPV) and linear sweep voltammetry (LSV) were separately used to investigate the interaction of NFR with HSA and interesting thermodynamics information was obtained from these studies. Secondly, new information including electrochemical behavior of NFR-HSA complex species, relative concentrations of the various reacting species and effects of NFR on the sub-structure of HSA was obtained by applying multivariate curve resolution-alternating least squares (MCR-ALS). In this case, a row- and column-wise augmented matrix was built with DPV, LSV, F and UVvis sub-matrices and resolved by MCR-ALS. Surprisingly, by this method two NFR-HSA complex species with different stoichiometries and different electrochemical behaviors were found. Furthermore, by the use of the recorded voltammetric and spectroscopic data the binding constants of complex species were computed by EQUISPEC (a hard-modeling algorithm). Finally, the binding of NFR to HSA was modeled by molecular modeling and molecular dynamics (MD) simulations methods. Excellent agreement was found between experimental and computational results. Both experimental and computational results suggested that the NFR binds mainly to the sub-domain IIA of HSA. PMID:23871980

  19. 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

  20. Correlations and symmetry of interactions influence collective dynamics of molecular motors

    NASA Astrophysics Data System (ADS)

    Celis-Garza, Daniel; Teimouri, Hamid; Kolomeisky, Anatoly B.

    2015-04-01

    Enzymatic molecules that actively support many cellular processes, including transport, cell division and cell motility, are known as motor proteins or molecular motors. Experimental studies indicate that they interact with each other and they frequently work together in large groups. To understand the mechanisms of collective behavior of motor proteins we study the effect of interactions in the transport of molecular motors along linear filaments. It is done by analyzing a recently introduced class of totally asymmetric exclusion processes that takes into account the intermolecular interactions via thermodynamically consistent approach. We develop a new theoretical method that allows us to compute analytically all dynamic properties of the system. Our analysis shows that correlations play important role in dynamics of interacting molecular motors. Surprisingly, we find that the correlations for repulsive interactions are weaker and more short-range than the correlations for the attractive interactions. In addition, it is shown that symmetry of interactions affect dynamic properties of molecular motors. The implications of these findings for motor proteins transport are discussed. Our theoretical predictions are tested by extensive Monte Carlo computer simulations.

  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. 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

  3. Bonding in Boranes and Their Interaction with Molecular Hydrogen at Extreme Conditions

    SciTech Connect

    Wang, Shibing; Mao, Wendy; Autrey, Thomas

    2009-10-14

    The effects of high pressure and temperature on the bonding in ammonia borane (AB), NH3BH3 and decaborane (DB), B10H14 and their interactions with molecular hydrogen (H2) were investigated using Raman spectroscopy in a diamond anvil cell. At 0.7 GPa, AB becomes amorphous between 120 and 127 °C, indicating a positive Clapeyron slope. Heated to 140 °C, AB begins to undergo decomposition to polyaminoborane. The amorphous and decomposed AB does not recrystallize back to AB during slow cooling to room temperature or upon application of high pressure up to 3 GPa, underscoring the challenge of rehydrogenation of decomposed AB. The molecular Raman modes broaden in the reacted phase, and the NH3 modes show no pressure dependence. DB was studied at room temperature up to 11 GPa. The observed frequency dependence with pressure (dv /dP) and mode Grüneisen parameters varied for different spectral groups, and a new transition was identified at approximately 3 GPa. In both DB and heated AB, we found that they could store additional H2 with the application of pressure. We estimate that we can store approximately 3 wt % H2 in heated AB at 3 GPa and 1 wt % H2 in DB at 4.5 GPa. "T.A. acknowledges support from the U.S. Department of Energy, Office of Basic Energy, Division of Chemical Sciences, Biosciences and Geosciences. PNNL is operated by Battelle."

  4. Bonding in boranes and their interaction with molecular hydrogen at extreme conditions.

    PubMed

    Wang, Shibing; Mao, Wendy L; Autrey, Tom

    2009-10-14

    The effects of high pressure and temperature on the bonding in ammonia borane (AB), NH(3)BH(3) and decaborane (DB), B(10)H(14) and their interactions with molecular hydrogen (H(2)) were investigated using Raman spectroscopy in a diamond anvil cell. At 0.7 GPa, AB becomes amorphous between 120 and 127 degrees C, indicating a positive Clapeyron slope. Heated to 140 degrees C, AB begins to undergo decomposition to polyaminoborane. The amorphous and decomposed AB does not recrystallize back to AB during slow cooling to room temperature or upon application of high pressure up to 3 GPa, underscoring the challenge of rehydrogenation of decomposed AB. The molecular Raman modes broaden in the reacted phase, and the NH(3) modes show no pressure dependence. DB was studied at room temperature up to 11 GPa. The observed frequency dependence with pressure (dnu/dP) and mode Gruneisen parameters varied for different spectral groups, and a new transition was identified at approximately 3 GPa. In both DB and heated AB, we found that they could store additional H(2) with the application of pressure. We estimate that we can store approximately 3 wt % H(2) in heated AB at 3 GPa and 1 wt % H(2) in DB at 4.5 GPa. PMID:19831453

  5. Bonding in boranes and their interaction with molecular hydrogen at extreme conditions

    SciTech Connect

    Wang, S.

    2010-02-24

    The effects of high pressure and temperature on the bonding in ammonia borane (AB), NH{sub 3}BH{sub 3} and decaborane (DB), B{sub 10}H{sub 14} and their interactions with molecular hydrogen (H{sub 2}) were investigated using Raman spectroscopy in a diamond anvil cell. At 0.7 GPa, AB becomes amorphous between 120 and 127 C, indicating a positive Clapeyron slope. Heated to 140 C, AB begins to undergo decomposition to polyaminoborane. The amorphous and decomposed AB does not recrystallize back to AB during slow cooling to room temperature or upon application of high pressure up to 3 GPa, underscoring the challenge of rehydrogenation of decomposed AB. The molecular Raman modes broaden in the reacted phase, and the NH{sub 3} modes show no pressure dependence. DB was studied at room temperature up to 11 GPa. The observed frequency dependence with pressure (d{sub {nu}}/dP) and mode Grueneisen parameters varied for different spectral groups, and a new transition was identified at approximately 3 GPa. In both DB and heated AB, we found that they could store additional H{sub 2} with the application of pressure. We estimate that we can store approximately 3 wt % H{sub 2} in heated AB at 3 GPa and 1 wt % H{sub 2} in DB at 4.5 GPa.

  6. 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.

  7. 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. PMID:26471667

  8. "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

  9. Analysis of Intermolecular Interactions Using Calculated Molecular Properties: AN AB Initio Quantum Chemical Study

    NASA Astrophysics Data System (ADS)

    Brinck, Nils Tore

    The objective of this study has been to investigate the use of computed molecular properties in predicting and interpreting intermolecular interactions. The molecular properties have been calculated rigorously from ab initio wave functions. We have found the electrostatic potential to be a good tool for the analysis of nonbonding intermolecular interactions. It is demonstrated that the calculated electrostatic potentials around carbon-halogen bonds can be used to explain the directional preferences of halogen interactions in crystals. We also show that the orientation of the molecules in weak gas phase complexes between dihalogens and Lewis bases can be rationalized from their electrostatic potentials. However an analysis of the bonding in boron trifluoride and boron trichloride and their complexes with ammonia indicates that the relative stabilities of these complexes are dictated by charge transfer rather than electrostatics. The higher binding affinity for boron trichloride compared to boron trifluoride is explained by the higher charge capacity of the former. This is contrary to the commonly accepted explanation, which is based on backbonding. A local charge separation index has been defined from surface electrostatic potentials. This provides a measure of local polarity, even for molecules with zero dipole moments. Average local ionization energies computed on molecular surfaces permit predictions of relative reactivities of various sites toward electrophilic attack. There is a very good relationship between {rm p}K_{a} and minima in |{I}({bf r}), designated as |{I}_{S,min }, for a series of azines and azoles. Excellent correlations have also been found between { rm p}K_{a} values for a variety of carbon, oxygen and nitrogen acids and the |{I}_{S,min} of their conjugate bases. A study of the electrostatic potentials and average local ionization energies of the V-VII hydrides of the first three rows of the periodic table and their anions demonstrates the

  10. Molecular Investigations into the Mechanics of a Muscle Anchoring Complex

    PubMed Central

    Bodmer, Nicholas K.; Theisen, Kelly E.; Dima, Ruxandra I.

    2015-01-01

    The titin-telethonin complex, essential for anchoring filaments in the Z-disk of the sarcomere, is composed of immunoglobulin domains. Surprisingly, atomic force microscopy experiments showed that it resists forces much higher than the typical immunoglobulin domain and that the force distribution is unusually broad. To investigate the origin of this behavior, we developed a multiscale simulation approach, combining minimalist and atomistic models (SOP-AT). By following the mechanical response of the complex on experimental timescales, we found that the mechanical stability of titin-telethonin is modulated primarily by the strength of contacts between telethonin and the two titin chains, and secondarily by the timescales of conformational excursions inside telethonin and the pulled titin domains. Importantly, the conformational transitions executed by telethonin in simulations support its proposed role in mechanosensing. Our SOP-AT computational approach thus provides a powerful tool for the exploration of the link between conformational diversity and the broadness of the mechanical response, which can be applied to other multidomain complexes. PMID:25954889

  11. 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

  12. 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

  13. 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…

  14. Cellular microbiology and molecular ecology of Legionella–amoeba interaction

    PubMed Central

    Richards, Ashley M.; Von Dwingelo, Juanita E.; Price, Christopher T.; Abu Kwaik, Yousef

    2013-01-01

    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

  15. 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

  16. Spectroscopic, viscositic and molecular modeling studies on the interaction of 3'-azido-daunorubicin thiosemicarbazone with DNA.

    PubMed

    Cui, Fengling; Liu, Qingfeng; Luo, Hongxia; Zhang, Guisheng

    2014-01-01

    A new daunorubicin has been synthesized and structurally characterized. The interaction of native calf thymus DNA (ctDNA) with 3'-azido-daunorubicin thiosemicarbazone (ADNRT) was investigated under simulated physiological conditions by multi-spectroscopic techniques, viscometric measurements and molecular modeling study. It concluded that ADNRT could intercalate into the base pairs of ctDNA, and the fluorescence quenching by ctDNA was static quenching type. Thermodynamic parameters calculated suggested that the binding of ADNRT to ctDNA was mainly driven by hydrophobic interactions. The relative viscosity of ctDNA increased with the addition of ADNRT, which confirmed the intercalation mode. Furthermore, molecular modeling studies corroborate the above experimental results. PMID:23974700

  17. 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.

  18. 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

  19. Interaction of Molecular Oxygen with Au (001) Surface

    NASA Astrophysics Data System (ADS)

    Pierce, Michael; Loheac, Andrew; Barbour, Andi; Komanicky, Vladimir; Ruffino, Anthony; You, Hoydoo

    Kinetics of dioxygen - Au (001) surface interaction has been studied at high temperature and near atmospheric pressures with in situ x-ray scattering measurements. We find that the hexagonal reconstruction (hex) of Au (001) surface lifts to (1×1) in the presence of dioxygen. The measured lifting rate constant vs. temperature shows a `volcano'-type behavior indicating that oxygen adsorption limits at high temperature while activation barrier of the lifting limits at low temperature. The pressure-temperature (PT) phase diagram obtained in our study shows three regions: hex at low P and T, (1×1) at high P and T, and coexistence of the hex and the (1×1) at the intermediate P and T. Funding provided by Research Corporation for Science Advancement. Work done at the Advanced Photon Source supported by the U.S. Department of Energy.

  20. Profiling of molecular interactions in real time using acoustic detection.

    PubMed

    Godber, Benjamin; Frogley, Mark; Rehak, Marian; Sleptsov, Alexander; Thompson, Kevin S J; Uludag, Yildiz; Cooper, Matthew A

    2007-04-15

    Acoustic sensors that exploit resonating quartz crystals to directly detect the binding of an analyte to a receptor are finding increasing utility in the quantification of clinically relevant analytes. We have developed a novel acoustic detection technology, which we term resonant acoustic profiling (RAP). This technology builds on the fundamental basics of the "quartz crystal microbalance" or "QCM" with several key additional features including two- or four-channel automated sample delivery, in-line referencing and microfluidic sensor 'cassettes' that are pre-coated with easy-to-use surface chemistries. Example applications are described for the quantification of myoglobin concentration and its interaction kinetics, and for the ranking of enzyme-cofactor specificities. PMID:17129723

  1. 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

  2. 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

  3. Beyond Standard Molecular Dynamics: Investigating the Molecular Mechanisms of G Protein-Coupled Receptors with Enhanced Molecular Dynamics Methods

    PubMed Central

    Johnston, Jennifer M.

    2014-01-01

    The majority of biological processes mediated by G Protein-Coupled Receptors (GPCRs) take place on timescales that are not conveniently accessible to standard molecular dynamics (MD) approaches, notwithstanding the current availability of specialized parallel computer architectures, and efficient simulation algorithms. Enhanced MD-based methods have started to assume an important role in the study of the rugged energy landscape of GPCRs by providing mechanistic details of complex receptor processes such as ligand recognition, activation, and oligomerization. We provide here an overview of these methods in their most recent application to the field. PMID:24158803

  4. Building Disease-Specific Drug-Protein Connectivity Maps from Molecular Interaction Networks and PubMed Abstracts

    PubMed Central

    Li, Jiao; Zhu, Xiaoyan; Chen, Jake Yue

    2009-01-01

    The recently proposed concept of molecular connectivity maps enables researchers to integrate experimental measurements of genes, proteins, metabolites, and drug compounds under similar biological conditions. The study of these maps provides opportunities for future toxicogenomics and drug discovery applications. We developed a computational framework to build disease-specific drug-protein connectivity maps. We integrated gene/protein and drug connectivity information based on protein interaction networks and literature mining, without requiring gene expression profile information derived from drug perturbation experiments on disease samples. We described the development and application of this computational framework using Alzheimer's Disease (AD) as a primary example in three steps. First, molecular interaction networks were incorporated to reduce bias and improve relevance of AD seed proteins. Second, PubMed abstracts were used to retrieve enriched drug terms that are indirectly associated with AD through molecular mechanistic studies. Third and lastly, a comprehensive AD connectivity map was created by relating enriched drugs and related proteins in literature. We showed that this molecular connectivity map development approach outperformed both curated drug target databases and conventional information retrieval systems. Our initial explorations of the AD connectivity map yielded a new hypothesis that diltiazem and quinidine may be investigated as candidate drugs for AD treatment. Molecular connectivity maps derived computationally can help study molecular signature differences between different classes of drugs in specific disease contexts. To achieve overall good data coverage and quality, a series of statistical methods have been developed to overcome high levels of data noise in biological networks and literature mining results. Further development of computational molecular connectivity maps to cover major disease areas will likely set up a new model for

  5. Building disease-specific drug-protein connectivity maps from molecular interaction networks and PubMed abstracts.

    PubMed

    Li, Jiao; Zhu, Xiaoyan; Chen, Jake Yue

    2009-07-01

    The recently proposed concept of molecular connectivity maps enables researchers to integrate experimental measurements of genes, proteins, metabolites, and drug compounds under similar biological conditions. The study of these maps provides opportunities for future toxicogenomics and drug discovery applications. We developed a computational framework to build disease-specific drug-protein connectivity maps. We integrated gene/protein and drug connectivity information based on protein interaction networks and literature mining, without requiring gene expression profile information derived from drug perturbation experiments on disease samples. We described the development and application of this computational framework using Alzheimer's Disease (AD) as a primary example in three steps. First, molecular interaction networks were incorporated to reduce bias and improve relevance of AD seed proteins. Second, PubMed abstracts were used to retrieve enriched drug terms that are indirectly associated with AD through molecular mechanistic studies. Third and lastly, a comprehensive AD connectivity map was created by relating enriched drugs and related proteins in literature. We showed that this molecular connectivity map development approach outperformed both curated drug target databases and conventional information retrieval systems. Our initial explorations of the AD connectivity map yielded a new hypothesis that diltiazem and quinidine may be investigated as candidate drugs for AD treatment. Molecular connectivity maps derived computationally can help study molecular signature differences between different classes of drugs in specific disease contexts. To achieve overall good data coverage and quality, a series of statistical methods have been developed to overcome high levels of data noise in biological networks and literature mining results. Further development of computational molecular connectivity maps to cover major disease areas will likely set up a new model for

  6. 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.

  7. Lipid interaction sites on channels, transporters and receptors: Recent insights from molecular dynamics simulations.

    PubMed

    Hedger, George; Sansom, Mark S P

    2016-10-01

    Lipid molecules are able to selectively interact with specific sites on integral membrane proteins, and modulate their structure and function. Identification and characterization of these sites are of importance for our understanding of the molecular basis of membrane protein function and stability, and may facilitate the design of lipid-like drug molecules. Molecular dynamics simulations provide a powerful tool for the identification of these sites, complementing advances in membrane protein structural biology and biophysics. We describe recent notable biomolecular simulation studies which have identified lipid interaction sites on a range of different membrane proteins. The sites identified in these simulation studies agree well with those identified by complementary experimental techniques. This demonstrates the power of the molecular dynamics approach in the prediction and characterization of lipid interaction sites on integral membrane proteins. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg. PMID:26946244

  8. [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

  9. Spectral broadening due to long-range Coulomb interactions in the molecular metal TTF-TCNQ

    NASA Astrophysics Data System (ADS)

    Cano-Cortés, L.; Dolfen, A.; Merino, J.; Behler, J.; Delley, B.; Reuter, K.; Koch, E.

    2007-04-01

    We employ density-functional theory to calculate realistic parameters for an extended Hubbard model of the molecular metal TTF-TCNQ. Considering both intra- and intermolecular screening in the crystal, we confirm the importance of the suspected longer-range Coulomb interactions along the molecular stacks, as well as inter-stack coupling. Contrary to past belief, these terms do not lead to the formation of a Wigner lattice, but simply broaden the spectral function.

  10. Spectroscopic Investigation on the Interaction of Titanate Nanotubes with Bovine Serum Albumin

    NASA Astrophysics Data System (ADS)

    Zhao, L. Z.; Zhao, Y. S.; Teng, H. H.; Shi, S. Y.; Ren, B. X.

    2014-09-01

    In order to understand the transport mechanism and evaluate the biological safety of titanate nanotubes, the interactions of titanate nanotubes (TNTs) with bovine serum albumin (BSA) were investigated by applying spectroscopic methods under simulated physiological conditions. After taking into account the inner filter effect, the fluorescence intensity of BSA was found to be significantly enhanced by the presence of TNTs, indicating that the microenvironment of tryptophan and tyrosine residues in BSA became more hydrophobic. In addition, the absorption spectra of BSA showed a hyperchromic effect around 280 nm as the concentration of TNTs increased, suggesting that TNTs changed the microenvironment of the tryptophan and tyrosine residues. This is consistent with the results from fl uorescence spectroscopy studies. However, circular dichroism spectroscopy revealed that no signifi cant conformational change in BSA occurred during the interaction. We believe that Trp-213 was buried more compactly in the internal hydrophobic region, and hydrophobicity increased around Trp-134 with increasing TNTs concentration. From a spectroscopic point of view, this work elucidates the interaction mechanism of titanate nanotubes with BSA, and the methods used in this paper can also be applied to explore the molecular mechanism underlying toxicity of other nanomaterials.

  11. 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.

  12. 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

  13. 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.

  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. PMID:24694366

  15. 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

  16. 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.

  17. Designed self-assembly of molecular necklaces using host-stabilized charge-transfer interactions.

    PubMed

    Ko, Young Ho; Kim, Kyungpil; Kang, Jin-Koo; Chun, Hyungphil; Lee, Jae Wook; Sakamoto, Shigeru; Yamaguchi, Kentaro; Fettinger, James C; Kim, Kimoon

    2004-02-25

    A novel approach to the noncovalent synthesis of molecular necklaces successfully led to the first quantitative self-assembly of a molecular necklace [6]MN, in which five small rings are threaded on a large ring, from 10 components. Our strategy involves the host-guest complex formation between the molecular host cucurbit[8]uril (CB[8]) and a guest molecule in which an electron donor and an electron acceptor unit are connected by a rigid linker with a proper angle, to form a cyclic oligomer through the host-stabilized intermolecular charge-transfer (CT) complex formation. In the structure of the molecular necklace [6]MN, five molecules of the guest form a cyclic framework by the intermolecular CT interactions, on which five CB[8] molecules are threaded with an arrangement reminiscent of a five-fold propeller. The molecular necklace measures approximately 3.7 nm in diameter and approximately 1.8 nm in thickness. PMID:14971915

  18. Energy frameworks: insights into interaction anisotropy and the mechanical properties of molecular crystals.

    PubMed

    Turner, Michael J; Thomas, Sajesh P; Shi, Ming W; Jayatilaka, Dylan; Spackman, Mark A

    2015-03-01

    We present an approach to understanding crystal packing via 'energy frameworks', that combines efficient calculation of accurate intermolecular interaction energies with a novel graphical representation of their magnitude. In this manner intriguing questions, such as why some crystals bend with an applied force while others break, and why one polymorph of a drug exhibits exceptional tabletability compared to others, can be addressed in terms of the anisotropy of the topology of pairwise intermolecular interaction energies. This approach is applied to a sample of organic molecular crystals with known bending, shearing and brittle behaviour, to illustrate its use in rationalising their mechanical behaviour at a molecular level. PMID:25525647

  19. Molecular interactions between nucleic acids and antitumor substances by Raman and NMR spectroscopy.

    PubMed

    Bertoluzza, A; Fagnano, C; Tosi, R; Tugnoli, V; Morelli, M A; Barbarella, G

    1986-01-01

    1-Methyladenosine (1-MeAdo) and protonated 1-Methyladenosine (1-MeAdo.H+) were chosen as a model to study the molecular interactions between the carcinogen dimethylsulphate (DMS) and the base adenine, and the interactions between the antitumoral electrophilic cis-diamminedichlorophatinum (II) (cis-Pt) and the methylation product of the base, respectively. Raman and multinuclear NMR studies show the molecular perturbations caused by the carcinogen on the base and those of the antitumoral substance on the reaction product base-carcinogen. PMID:3813493

  20. Thermodynamic evaluation of aromatic CH/π interactions and rotational entropy in a molecular rotor.

    PubMed

    Pérez-Estrada, Salvador; Rodríguez-Molina, Braulio; Xiao, Leilei; Santillan, Rosa; Jiménez-Osés, Gonzalo; Houk, K N; Garcia-Garibay, Miguel A

    2015-02-18

    A molecular rotor built with a stator formed by two rigid 9β-mestranol units having a 90° bent angle linked to a central phenylene rotator has an ideal structure to examine aromatic CH/π interactions. Energies and populations of the multiple solution conformations from quantum-mechanical calculations and molecular dynamics simulations were combined with variable-temperature (VT) (1)H NMR data to establish the enthalpy of this interaction and the entropy associated with rotation about a single bond. Rotational dynamics in the solid state were determined via VT cross-polarization magic-angle spinning (13)C NMR spectroscopy. PMID:25635355

  1. 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.

  2. 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. PMID:26372227

  3. Molecular interactions of mussel protective coating protein, mcfp-1, from Mytilus californianus.

    PubMed

    Lu, Qingye; Hwang, Dong Soo; Liu, Yang; Zeng, Hongbo

    2012-02-01

    Protective coating of the byssus of mussels (Mytilus sp.) has been suggested as a new paradigm of medical coating due to its high extensibility and hardness co-existence without their mutual detriment. The only known biomacromolecule in the extensible and tough coating on the byssus is mussel foot protein-1 (mfp-1), which is made up with positively charged residues (~20 mol%) and lack of negatively charged residues. Here, adhesion and molecular interaction mechanisms of Mytilus californianus foot protein-1 (mcfp-1) from California blue mussel were investigated using a surface forces apparatus (SFA) in buffer solutions of different ionic concentrations (0.2-0.7 M) and pHs (3.0-5.5). Strong and reversible cohesion between opposed positively charged mcfp-1 films was measured in 0.1 M sodium acetate buffer with 0.1 M KNO(3). Cohesion of mcfp-1 was gradually reduced with increasing the ionic strength, but was not changed with pH variations. Oxidation of 3,4-dihydroxyphenylalanine (DOPA) residues of mcfp-1, a key residue for adhesive and coating proteins of mussel, didn't change the cohesion strength of mcfp-1 films, but the addition of chemicals with aromatic groups (i.e., aspirin and 4-methylcatechol) increased the cohesion. These results suggest that the cohesion of mcfp-1 films is mainly mediated by cation-π interactions between the positively charged residues and benzene rings of DOPA and other aromatic amino acids (~20 mol% of total amino acids of mcfp-1), and π-π interactions between the phenyl groups in mcfp-1. The adhesion mechanism obtained for the mcfp-1 proteins provides important insight into the design and development of functional biomaterials and coatings mimicking the extensible and robust mussel cuticle coating. PMID:22138031

  4. Structural investigation of the interactions of biotinylruthenocene with avidin.

    PubMed

    Strzelczyk, Paweł; Bujacz, Anna; Plażuk, Damian; Zakrzewski, Janusz; Bujacz, Grzegorz

    2013-06-25

    The crystal structure of avidin, a protein from hen egg white, was determined in the form of a complex with biotinylruthenocene. This biotin-derived organometallic ligand is a potential anticancer agent for targeted therapy based upon avidin-biotin technology. Isothermal titration calorimetry experiments, involving avidin complexes with biotin (vitamin H or B7) derivatives, show differences in their affinity to the protein in comparison to its avidin-biotin complex, the strongest known biochemical interaction in Nature. The crystal structure of the first complex of avidin with biotinylruthenocene, determined at 2.5Å resolution (PDB: 4I60), shows unique interactions of the ruthenocene moiety with avidin. Biotin derivatives exhibit weaker affinity to avidin then biotin, which allows their wider use in biotechnology. The specific properties of biotinylruthenocene and the knowledge of its interactions with avidin may be useful in biochemical, medical, and nanotechnological applications. PMID:23603015

  5. 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.

  6. 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

  7. 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

  8. 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

  9. From molecular interaction to acute promyelocytic leukemia: Calculating leukemogenesis and remission from endogenous molecular-cellular network.

    PubMed

    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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. Theoretical investigation of the molecular structures and excitation spectra of triphenylamine and its derivatives.

    PubMed

    Sumimoto, Michinori; Yokogawa, Daisuke; Komeda, Masahiro; Yamamoto, Hidetoshi; Hori, Kenji; Fujimoto, Hitoshi

    2011-10-15

    The molecular geometries, electronic structures, and excitation energies of NPh(3), NPh(2)Me, 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. PMID:21795108

  15. 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.

  16. 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

  17. The interaction of hydrogen with an Fe vacancy: a molecular orbital simulation

    NASA Astrophysics Data System (ADS)

    Irigoyen, B.; Ferullo, R.; Castellani, N.; Juan, A.

    1996-05-01

    The semi-empirical atom superposition and electron delocalization molecular orbital (ASED-MO) theory was used to study the H - Fe interaction present during the adsorption of monotomic hydrogen on Fe(110) and the subsequent absorption of the hydrogen atom in a bulk Fe vacancy. For that purpose calculations were carried out using clusters with 53 and 50 atoms, respectively. Results indicate that, in general, the hydrogen - iron interaction is stronger near the surface and near the vacancy.

  18. 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

  19. Elizabethkingia anophelis: molecular manipulation and interactions with mosquito hosts.

    PubMed

    Chen, Shicheng; Bagdasarian, Michael; Walker, Edward D

    2015-03-01

    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

  20. 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

  1. 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. PMID:25808513

  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. 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.

  4. 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

  5. Hepatitis C virus RNA: molecular switches mediated by long-range RNA–RNA interactions?

    PubMed Central

    Shetty, Sumangala; Stefanovic, Snezana; Mihailescu, Mihaela Rita

    2013-01-01

    Multiple conserved structural cis-acting regulatory elements have been recognized both in the coding and untranslated regions (UTRs) of the hepatitis C virus (HCV) genome. For example, the cis-element 5BSL3.2 in the HCV-coding region has been predicted to use both its apical and internal loops to interact with the X RNA in the 3′-UTR, with the IIId domain in the 5′-UTR and with the Alt sequence in the coding region. Additionally, the X RNA region uses a palindromic sequence that overlaps the sequence required for the interaction with 5BSL3.2, to dimerize with another HCV genome. The ability of the 5BSL3.2 and X RNA regions to engage in multi-interactions suggests the existence of one or more molecular RNA switches which may regulate different steps of the HCV life cycle. In this study, we used biophysical methods to characterize the essential interactions of these HCV cis-elements at the molecular level. Our results indicate that X RNA interacts with 5BSL3.2 and another X RNA molecule by adopting two different conformations and that 5BSL3.2 engages simultaneously in kissing interactions using its apical and internal loops. Based on these results, we propose a mode of action for possible molecular switches involving the HCV RNA. PMID:23275555

  6. Fluorescence Correlation Spectroscopy Simulations of Photophysical Phenomena and Molecular Interactions: A Molecular Dynamics/Monte Carlo Approach

    PubMed Central

    Dix, James A.; Hom, Erik F. Y.; Verkman, A. S.

    2011-01-01

    Fluorescence correlation spectroscopy (FCS) is being applied increasingly to study diffusion and interactions of fluorescently labeled macromolecules in complex biological systems. Fluctuations in detected fluorescence, δF(t), are expressed as time-correlation functions, G(τ), and photon-count histograms, P(k;ΔT). Here, we developed a generalized simulation approach to compute G(τ) and P(k;ΔT) for complex systems with arbitrary geometry, photophysics, diffusion, and macromolecular interactions. G(τ) and P(k;ΔT) were computed from δF(t) generated by a Brownian dynamics simulation of single-molecule trajectories followed by a Monte Carlo simulation of fluorophore excitation and detection statistics. Simulations were validated by comparing analytical and simulated G(τ) and P(k;ΔT) for diffusion of noninteracting fluorophores in a three-dimensional Gaussian excitation and detection volume. Inclusion of photobleaching and triplet-state relaxation produced significant changes in G(τ) and P(k;ΔT). Simulations of macromolecular interactions and complex diffusion were done, including transient fluorophore binding to an immobile matrix, cross-correlation analysis of interacting fluorophores, and anomalous sub- and superdiffusion. The computational method developed here is generally applicable for simulating FCS measurements on systems complicated by fluorophore interactions or molecular crowding, and experimental protocols for which G(τ) and P(k;ΔT) cannot be computed analytically. PMID:16471761

  7. 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

  8. 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

  9. 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

  10. Challenging AQP4 druggability for NMO-IgG antibody binding using molecular dynamics and molecular interaction fields.

    PubMed

    Mangiatordi, Giuseppe Felice; Alberga, Domenico; Siragusa, Lydia; Goracci, Laura; Lattanzi, Gianluca; Nicolotti, Orazio

    2015-07-01

    Neuromyelitis optica (NMO) is a multiple sclerosis-like immunopathology disease affecting optic nerves and the spinal cord. Its pathological hallmark is the deposition of a typical immunoglobulin, called NMO-IgG, against the water channel Aquaporin-4 (AQP4). Preventing NMO-IgG binding would represent a valuable molecular strategy for a focused NMO therapy. The recent observation that aspartate in position 69 (D69) is determinant for the formation of NMO-IgG epitopes prompted us to carry out intensive Molecular Dynamics (MD) studies on a number of single-point AQP4 mutants. Here, we report a domino effect originating from the point mutation at position 69: we find that the side chain of T62 is reoriented far from its expected position leaning on the lumen of the pore. More importantly, the strength of the H-bond interaction between L53 and T56, at the basis of the loop A, is substantially weakened. These events represent important pieces of a clear-cut mechanistic rationale behind the failure of the NMO-IgG binding, while the water channel function as well as the propensity to aggregate into OAPs remains unaltered. The molecular interaction fields (MIF)-based analysis of cavities complemented MD findings indicating a putative binding site comprising the same residues determining epitope reorganization. In this respect, docking studies unveiled an intriguing perspective to address the future design of small drug-like compounds against NMO. In agreement with recent experimental observations, the present study is the first computational attempt to elucidate NMO-IgG binding at the molecular level, as well as a first effort toward a less elusive AQP4 druggability. PMID:25839357

  11. Delineating solute-solvent interactions in binary mixtures of ionic liquids in molecular solvents and preferential solvation approach.

    PubMed

    Khupse, Nageshwar D; Kumar, Anil

    2011-02-01

    The effect of solute-solvent and solvent-solvent interactions on the preferential solvation of solvatochromic indicators in binary mixtures of ionic liquids with molecular solvents has been investigated. The binary mixtures of the pyridinium-based ionic liquids 1-butylpyridinium tetrafluoroborate ([BP][BF4]), 1-butyl-3-methylpyridinium tetrafluoroborate ([3-MBP][BF4]), and 1-butyl-4-methylpyridinium tetrafluoroborate ([4-MBP][BF4]) with molecular solvents like water, methanol, and dichloromethane have been selected for this investigation. The effect of addition of ionic liquids to molecular solvents on the polarity parameters E(T)(N), Kamlet-Taft parameters, hydrogen bond donor ability (HBD) (α), hydrogen bond acceptor ability (HBA) (β), and polarizability (π*) was obtained. The polarity parameters of the mixture display nonideality on addition of ionic liquids to water and dichloromethane. On the other hand, strong synergetic effects were seen in the ionic liquid-methanol binary mixtures. The preferential solvation models have been employed to analyze the collected data in order to achieve information on solute-solvent interactions in these binary mixtures. PMID:21142058

  12. 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. PMID:25587872

  13. 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.

  14. Structural investigations into the interaction of hemoglobin and part structures with bacterial endotoxins.

    PubMed

    Howe, Jörg; Garidel, Patrick; Roessle, Manfred; Richter, Walter; Alexander, Christian; Fournier, Karin; Mach, Jean Pierre; Waelli, Thierry; Gorczynski, Reginald M; Ulmer, Artur J; Zähringer, Ulrich; Hartmann, Alfred; Rietschel, Ernst Th; Brandenburg, Klaus

    2008-02-01

    An understanding of details of the interaction mechanisms of bacterial endotoxins (lipopolysaccharide, LPS) with the oxygen transport protein hemoglobin is still lacking, despite its high biological relevance. Here, a biophysical investigation into the endotoxin:hemoglobin interaction is presented which comprises the use of various rough mutant LPS as well as free lipid A; in addition to the complete hemoglobin molecule from fetal sheep extract, also the partial structure alpha-chain and the heme-free sample are studied. The investigations comprise the determination of the gel-to-liquid crystalline phase behaviour of the acyl chains of LPS, the ultrastructure (type of aggregate structure and morphology) of the endotoxins, and the incorporation of the hemoglobins into artificial immune cell membranes and into LPS. Our data suggest a model for the interaction between Hb and LPS in which hemoglobins do not react strongly with the hydrophilic or with the hydrophobic moiety of LPS, but with the complete endotoxin aggregate. Hb is able to incorporate into LPS with the longitudinal direction parallel to the lipid A double-layer. Although this does not lead to a strong disturbance of the LPS acyl chain packing, the change of the curvature leads to a slightly conical molecular shape with a change of the three-dimensional arrangement from unilamellar into cubic LPS aggregates. Our previous results show that cubic LPS structures exhibit strong endotoxic activity. The property of Hb on the physical state of LPS described here may explain the observation of an increase in LPS-mediating endotoxicity due to the action of Hb. PMID:18387918

  15. 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

  16. Conserved molecular switch interactions in modeled cardioactive RF-NH2 peptide receptors: Ligand binding and activation.

    PubMed

    Rasmussen, M; Leander, M; Ons, S; Nichols, R

    2015-09-01

    Peptides may act through G protein-coupled receptors to influence cardiovascular performance; thus, delineating mechanisms involved in signaling is a molecular-based strategy to influence health. Molecular switches, often represented by conserved motifs, maintain a receptor in an inactive state. However, once the switch is broken, the transmembrane regions move and activation occurs. The molecular switches of Drosophila melanogaster myosuppressin (MS) receptors were previously identified to include a unique ionic lock and novel 3-6 lock, as well as transmission and tyrosine toggle switches. In addition to MS, cardioactive ligands structurally related by a C-terminal RF-NH2 include sulfakinin, neuropeptide F (NPF), short NPF, and FMRF-NH2-containing peptide subfamilies. We hypothesized receptor molecular switch motifs were conserved within a RF-NH2 subfamily and across species. Thus, we investigated RF-NH2 receptor (RFa-R) molecular switches in D. melanogaster, Tribolium castaneum, Anopheles gambiae, Rhodnius prolixus, and Bombyx mori. Adipokinetic hormone (AKH), which does not contain a RF-NH2, was also examined. The tyrosine toggle switch and ionic lock showed a higher degree of conservation within a RF-NH2 subfamily than the transmission switch and 3-7 lock. AKH receptor motifs were not representative of a RF-NH2 subfamily. The motifs and interactions of switches in the RFa-Rs were consistent with receptor activation and ligand-specific binding. PMID:26211890

  17. USE OF MOLECULAR MODELING TO DETERMINE THE INTERACTION AND COMPETITION OF GASES WITHIN COAL FOR CARBON DIOXIDE SEQUESTRATION

    SciTech Connect

    Jeffrey D. Evanseck; Jeffry D. Madura; Jonathan P. Mathews

    2005-05-27

    We have made progress in carrying out large scale molecular dynamics simulations using the CHARMM force field in order to refine our coal/guest interactions. There have been two issues facing us over the last year. First, we have had to create a completely new topology and parameter definition for coal. Since we are using a classical force field, we have adopted the strategy of treating coal composed of individual common fragments based upon a distribution of mass, composition, and bonding. Our procedure is similar to treating a protein as being composed of the discrete set of amino acids. Second, we have had to incorporate the quality CO{sub 2} parameters that we have developed over the last two years. There are the geometric and arithmetic procedures, which we have successfully implemented. We have utilized computational molecular modeling to generate a state-of-the-art large scale structural representation of a bituminous coal of low volatile bituminous rank. This structure(s) has been used to investigate the molecular forces between the bituminous coal structure (or idealized pores) and the molecular species CH{sub 4} and CO{sub 2}. We are close to carrying out molecular dynamics simulations, which will allow us to explore and test the newly created model of coal.

  18. Structural aspects of the solvation shell of lysine and acetylated lysine: A Car-Parrinello and classical molecular dynamics investigation

    NASA Astrophysics Data System (ADS)

    Carnevale, V.; Raugei, S.

    2009-12-01

    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.

  19. 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.

  20. 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

  1. 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.

  2. 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...

  3. Detection of molecular interactions at membrane surfaces through colloid phase transitions

    NASA Astrophysics Data System (ADS)

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

    2004-01-01

    The molecular architecture of-and biochemical processes within-cell membranes play important roles in all living organisms, with many drugs and infectious disease agents targeting membranes. Experimental studies of biochemical reactions on membrane surfaces are challenging, as they require a membrane environment that is fluid (like cell membranes) but nevertheless allows for the efficient detection and characterization of molecular interactions. One approach uses lipid membranes supported on solid substrates such as silica or polymers: although the membrane is trapped near the solid interface, it retains natural fluidity and biological functionality and can be implanted with membrane proteins for functional studies. But the detection of molecular interactions involving membrane-bound species generally requires elaborate techniques, such as surface plasmon resonance or total internal reflection fluorescence microscopy. Here we demonstrate that colloidal phase transitions of membrane-coated silica beads provide a simple and label-free method for monitoring molecular interactions on lipid membrane surfaces. By adjusting the lipid membrane composition and hence the pair interaction potential between the membrane-supporting silica beads, we poise our system near a phase transition so that small perturbations on the membrane surface induce dramatic changes in the macroscopic organization of the colloid. We expect that this approach, used here to probe with high sensitivity protein binding events at membrane surfaces, can be applied to study a broad range of cell membrane processes.

  4. Examining the molecular interaction between potato (Solanum tuberosum) and Colorado potato beetle Leptinotarsa decemlineata (Say)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Colorado potato beetle (CPB) is a leading pest of solanaceous plants; however, little is known about its molecular interaction with the potato plant. Using the 11,421 EST array solanaceae microarray profiling services at TIGR, we have identified genes that are differentially expressed in potato leav...

  5. 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.

  6. 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…

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. Investigation of ethanol infiltration into demineralized dentin collagen fibrils using molecular dynamics simulations.

    PubMed

    Jee, Sang Eun; Zhou, Jienfeng; Tan, Jianquo; Breschi, Lorenzo; Tay, Franklin R; Grégoire, Geneviève; Pashley, David H; Jang, Seung Soon

    2016-05-01

    The purpose of this study is to investigate the interaction of neat ethanol with bound and non-bound water in completely demineralized dentin that is fully hydrated, using molecular dynamics (MD) simulation method. The key to creating ideal resin-dentin bonds is the removal of residual free water layers and its replacement by ethanol solvent in which resin monomers are soluble, using the ethanol wet-bonding technique. The test null hypotheses were that ethanol cannot remove any collagen-bound water, and that ethanol cannot infiltrate into the spacing between collagen triple helix due to narrow interlayer spacing. Collagen fibrillar structures of overlap and gap regions were constructed by aligning the collagen triple helix of infinite length in hexagonal packing. Three layers of the water molecules were specified as the layers of 0.15-0.22nm, 0.22-0.43nm and 0.43-0.63nm from collagen atoms by investigating the water distribution surrounding collagen molecules. Our simulation results show that ethanol molecules infiltrated into the intermolecular spacing in the gap region, which increased due to the lateral shrinkage of the collagen structures in contact with ethanol solution, while there was no ethanol infiltration observed in the overlap region. Infiltrated ethanol molecules in the gap region removed residual water molecules via modifying mostly the third water layer (50% decrease), which would be considered as a loosely-bound water layer. The first and second hydration layers, which would be considered as tightly bound water layers, were not removed by the ethanol molecules, thus maintaining the helical structures of the collagen molecules. PMID:26969524

  13. Investigations of the intermolecular forces between RDX and polyethylene by force-distance spectroscopy and molecular dynamics simulations.

    PubMed

    Taylor, D E; Strawhecker, K E; Shanholtz, E R; Sorescu, D C; Sausa, R C

    2014-07-10

    The development of novel nanoenergetic materials with enhanced bulk properties requires an understanding of the intermolecular interactions occurring between molecular components. We investigate the surface interactions between 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX) and polyethylene (PE) crystals on the basis of combined use of molecular dynamics (MD) simulations and force-distance spectroscopy, in conjunction with Lifshitz macroscopic theory of van der Waals forces between continuous materials. The binding energy in the RDX-PE system depends both on the degree of PE crystallinity and on the RDX crystal face. Our MD simulations yield binding energies of approximately 132 and 120 mJ/m(2) for 100% amorphous and 100% crystalline PE on RDX (210), respectively. The average value is about 36% greater than our experimental value of 81 ± 15 mJ/m(2) for PE (∼48% amorphous) on RDX (210). By comparison, Liftshitz theory predicts a value of about 79 mJ/m(2) for PE interacting with RDX. Our MD simulations also predict larger binding energies for both amorphous and crystalline PE on RDX (210) compared to the RDX (001) surface. Analysis of the interaction potential indicates that about 60% of the binding energy in the PE-RDX system is due to attractive interactions between HPE-ORDX and CPE-NRDX pairs of atoms. Further, amorphous PE shows a much longer interaction distance than crystalline PE with the (210) and (001) RDX surfaces due to the possibility of larger polymer elongations in the case of amorphous PE as strain is applied. Also, we report estimates of the binding energies of energetic materials RDX and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) with PE, propylene, polystyrene, and several fluorine-containing polymers using Lifshitz theory and compare these with reported MD calculations. PMID:24922563

  14. Adsorption interaction in the molecular hydrogen-aluminophosphate AlPO-5 zeolite system

    NASA Astrophysics Data System (ADS)

    Grenev, I. V.; Gavrilov, V. Yu.

    2015-03-01

    The adsorption interaction between molecular hydrogen and atoms forming the lattice of AlPO-5 zeolite is studied. The potential of intramolecular interaction is calculated by summing the potentials of individual pairwise H2-O(Al, P) interactions in a fragment of the zeolite structure with a volume of ˜32 nm3. Isopotential surfaces are constructed that allow determination of the shape of zeolite microchannels and the places of the preferential localization of sorbate molecules in the porous space. The calculated and experimental values of the Henry constant of H2 adsorption on AlPO-5 at 77 K are compared.

  15. Rotational Spectromicroscopy: Imaging the Orbital Interaction between Molecular Hydrogen and an Adsorbed Molecule

    NASA Astrophysics Data System (ADS)

    Li, Shaowei; Yuan, Dingwang; Yu, Arthur; Czap, Gregory; Wu, Ruqian; Ho, W.

    2015-05-01

    A hydrogen molecule can diffuse freely on the surface and be trapped above an adsorbed molecule within the junction of a scanning tunneling microscope. The trapped dihydrogen exhibits the properties of a free rotor. Here we show that the intermolecular interaction between dihydrogen and Mg-porphyrin (MgP) can be visualized by imaging j =0 to 2 rotational excitation of dihydrogen. The interaction leads to a weakened H-H bond and modest electron donation from the dihydrogen to the lowest unoccupied molecular orbital of MgP, a process similarly observed for the interaction between dihydrogen and an adsorbed Au atom.

  16. Rotational Spectromicroscopy: Imaging the Orbital Interaction between Molecular Hydrogen and an Adsorbed Molecule.

    PubMed

    Li, Shaowei; Yuan, Dingwang; Yu, Arthur; Czap, Gregory; Wu, Ruqian; Ho, W

    2015-05-22

    A hydrogen molecule can diffuse freely on the surface and be trapped above an adsorbed molecule within the junction of a scanning tunneling microscope. The trapped dihydrogen exhibits the properties of a free rotor. Here we show that the intermolecular interaction between dihydrogen and Mg-porphyrin (MgP) can be visualized by imaging j=0 to 2 rotational excitation of dihydrogen. The interaction leads to a weakened H-H bond and modest electron donation from the dihydrogen to the lowest unoccupied molecular orbital of MgP, a process similarly observed for the interaction between dihydrogen and an adsorbed Au atom. PMID:26047242

  17. Molecular Graphics and Chemistry.

    ERIC Educational Resources Information Center

    Weber, Jacques; And Others

    1992-01-01

    Explains molecular graphics, i.e., the application of computer graphics techniques to investigate molecular structure, function, and interaction. Structural models and molecular surfaces are discussed, and a theoretical model that can be used for the evaluation of intermolecular interaction energies for organometallics is described. (45…

  18. Genetically Encoded Molecular Tension Probe for Tracing Protein-Protein Interactions in Mammalian Cells.

    PubMed

    Kim, Sung Bae; Nishihara, Ryo; Citterio, Daniel; Suzuki, Koji

    2016-02-17

    Optical imaging of protein-protein interactions (PPIs) facilitates comprehensive elucidation of intracellular molecular events. We demonstrate an optical measure for visualizing molecular tension triggered by any PPI in mammalian cells. Twenty-three kinds of candidate designs were fabricated, in which a full-length artificial luciferase (ALuc) was sandwiched between two model proteins of interest, e.g., FKBP and FRB. One of the designs greatly enhanced the bioluminescence in response to varying concentrations of rapamycin. It is confirmed with negative controls that the elevated bioluminescence is solely motivated from the molecular tension. The probe design was further modified toward eliminating the C-terminal end of ALuc and was found to improve signal-to-background ratios, named "a combinational probe". The utilities were elucidated with detailed substrate selectivity, bioluminescence imaging of live cells, and different PPI models. This study expands capabilities of luciferases as a tool for analyses of molecular dynamics and cell signaling in living subjects. PMID:26322739

  19. Multispectroscopic and molecular modeling studies on the interaction of two curcuminoids with β-lactoglobulin

    NASA Astrophysics Data System (ADS)

    Mohammadi, F.; Sahihi, M.; Bordbar, A. Khalegh

    2015-04-01

    This study demonstrates the binding properties of bisdemethoxycurcumin (BDMC) and diacetylbisdemethoxycurcumin (DABC) as bioactive curcuminoids with bovine β-lactoglobulin (BLG) variant B using fluorescence and circular dichroism (CD) spectroscopy; molecular docking, and molecular dynamics simulation methods. The estimated binding constants for BLG-BDMC and BLG-DABC complexes were (8.99 ± 0.10) × 104 M-1 and (1.87 ± 0.10) × 102 M-1, respectively. The distances between BLG and these curcuminoids were obtained based on the Förster's theory of non-radiative energy transfer. Molecular docking studies revealed the binding of BDMC and DABC to the protein surface cleft of protein by formation of four and one hydrogen bonds, respectively. Finally, molecular dynamics simulation results represent the conformational changes of BLG due to its interaction with BDMC. Also, the profiles of atomic fluctuations signified the rigidity of ligand binding site during the simulation.

  20. Investigation of ODE integrators using interactive graphics. [Ordinary Differential Equations

    NASA Technical Reports Server (NTRS)

    Brown, R. L.

    1978-01-01

    Two FORTRAN programs using an interactive graphic terminal to generate accuracy and stability plots for given multistep ordinary differential equation (ODE) integrators are described. The first treats the fixed stepsize linear case with complex variable solutions, and generates plots to show accuracy and error response to step driving function of a numerical solution, as well as the linear stability region. The second generates an analog to the stability region for classes of non-linear ODE's as well as accuracy plots. Both systems can compute method coefficients from a simple specification of the method. Example plots are given.

  1. Investigation on interaction between Ligupurpuroside A and pepsin by spectroscopic and docking methods

    NASA Astrophysics Data System (ADS)

    Shen, Liangliang; Xu, Hong; Huang, Fengwen; Li, Yi; Xiao, Huafeng; Yang, Zhen; Hu, Zhangli; He, Zhendan; Zeng, Zheling; Li, Yinong

    2015-01-01

    Ligupurpuroside A is one of the major glycoside in Ku-Din-Cha, a type of Chinese functional tea. In order to better understand its digestion and metabolism in humans, the interaction between Ligupurpuroside A and pepsin has been investigated by fluorescence spectra, UV-vis absorption spectra and synchronous fluorescence spectra along with molecular docking method. The fluorescence experiments indicate that Ligupurpuroside A can effectively quench the intrinsic fluorescence of pepsin through a combined quenching way at the low concentration of Ligupurpuroside A, and a static quenching procedure at the high concentration. The binding constant, binding sites of Ligupurpuroside A with pepsin have been calculated. The thermodynamic analysis suggests that non-covalent reactions, including electrostatic force, hydrophobic interaction and hydrogen bond are the main forces stabilizing the complex. According to the Förster's non-radiation energy transfer theory, the binding distance between pepsin and Ligupurpuroside A was calculated to be 3.15 nm, which implies that energy transfer occurs between pepsin and Ligupurpuroside A. Conformation change of pepsin was observed from UV-vis absorption spectra and synchronous fluorescence spectra under experimental conditions. In addition, all these experimental results have been validated by the protein-ligand docking studies which show that Ligupurpuroside A is located in the cleft between the domains of pepsin.

  2. 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.

  3. 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.

  4. 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.

  5. Novel Diagnostics to Investigate Turbine-Turbine Interactions

    NASA Astrophysics Data System (ADS)

    Balakumar, B. J.; Pol, S.

    2011-11-01

    Strong aerodynamic interactions between upstream wind turbine wakes and downstream turbine blades cause fatigue loads and reduce turbine reliability. The wake structure also mediates the vertical flux of momentum and affects the power output of downstream turbines in turbine arrays. Despite their importance, our current understanding of wake-turbine interactions and wake structure is limited, especially under complex operating conditions such as yawed inflow and dynamic stall. Traditional diagnostics such as sonic anemometers, hotwires, and lidars suffer from interference and accuracy limitations and prove inadequate. At LANL, we have developed a Large Field-of-View Particle Image Velocimeter (LF-PIV) capable of measuring 3 m ×1 m (per camera) wake and inflow regions around a 5m-scale turbine. This scalable diagnostic operates in conjunction with a hub-mounted Rotating PIV (R-PIV) diagnostic to observe blade boundary layer and separation while the turbine is in operation. We discuss the diagnostic development challenges, solutions used to overcome these, and the interesting physics that these diagnostics promise to illuminate. Supported by LANL LDRD grant 20100040DR (PI: Curtt Ammerman).

  6. Electrostatic unfolding and interactions of albumin driven by pH changes: a molecular dynamics study.

    PubMed

    Baler, K; Martin, O A; Carignano, M A; Ameer, G A; Vila, J A; Szleifer, I

    2014-01-30

    A better understanding of protein aggregation is bound to translate into critical advances in several areas, including the treatment of misfolded protein disorders and the development of self-assembling biomaterials for novel commercial applications. Because of its ubiquity and clinical potential, albumin is one of the best-characterized models in protein aggregation research; but its properties in different conditions are not completely understood. Here, we carried out all-atom molecular dynamics simulations of albumin to understand how electrostatics can affect the conformation of a single albumin molecule just prior to self-assembly. We then analyzed the tertiary structure and solvent accessible surface area of albumin after electrostatically triggered partial denaturation. The data obtained from these single protein simulations allowed us to investigate the effect of electrostatic interactions between two proteins. The results of these simulations suggested that hydrophobic attractions and counterion binding may be strong enough to effectively overcome the electrostatic repulsions between the highly charged monomers. This work contributes to our general understanding of protein aggregation mechanisms, the importance of explicit consideration of free ions in protein solutions, provides critical new insights about the equilibrium conformation of albumin in its partially denatured state at low pH, and may spur significant progress in our efforts to develop biocompatible protein hydrogels driven by electrostatic partial denaturation. PMID:24393011

  7. Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics Study

    PubMed Central

    2015-01-01

    A better understanding of protein aggregation is bound to translate into critical advances in several areas, including the treatment of misfolded protein disorders and the development of self-assembling biomaterials for novel commercial applications. Because of its ubiquity and clinical potential, albumin is one of the best-characterized models in protein aggregation research; but its properties in different conditions are not completely understood. Here, we carried out all-atom molecular dynamics simulations of albumin to understand how electrostatics can affect the conformation of a single albumin molecule just prior to self-assembly. We then analyzed the tertiary structure and solvent accessible surface area of albumin after electrostatically triggered partial denaturation. The data obtained from these single protein simulations allowed us to investigate the effect of electrostatic interactions between two proteins. The results of these simulations suggested that hydrophobic attractions and counterion binding may be strong enough to effectively overcome the electrostatic repulsions between the highly charged monomers. This work contributes to our general understanding of protein aggregation mechanisms, the importance of explicit consideration of free ions in protein solutions, provides critical new insights about the equilibrium conformation of albumin in its partially denatured state at low pH, and may spur significant progress in our efforts to develop biocompatible protein hydrogels driven by electrostatic partial denaturation. PMID:24393011

  8. Molecular Dynamics Simulations of the Interactions Between Tungsten Dust and Beryllium Plasma-Facing Material

    NASA Astrophysics Data System (ADS)

    Niu, Guojian; Li, Xiaochun; Xu, Qian; Yang, Zhongshi; Luo, Guangnan

    2015-12-01

    In the present research, molecular dynamics simulation is applied to study the interactions between tungsten dusts and a beryllium plasma-facing material surface. Calculation results show that it is quite difficult for nanometer-size dust particles to damage the plasma-facing material surface, which is different from the micrometer-size ones. The reason may be the size difference between dust and crystal grains. The depth of dust penetration into plasma-facing materials is closely related to the incident velocity, and the impacting angle also plays an important role. Dust and material surface damage is also investigated. Results show that both incident velocity and angle can significantly influence the damage. supported by the National Magnetic Confinement Fusion Science Program of China (Nos. 2013GB105001, 2013GB105002, and 2015GB109001), National Natural Science Foundation of China (Nos. 11205198, 11305213 and 11405201), as well as Technological Development Grant of Hefei Science Center of CAS (No. 2014TDG-HSC003)

  9. Interaction of Curcumin with PEO-PPO-PEO block copolymers: a molecular dynamics study.

    PubMed

    Samanta, Susruta; Roccatano, Danilo

    2013-03-21

    Curcumin, a naturally occurring drug molecule, has been extensively investigated for its various potential usages in medicine. Its water insolubility and high metabolism rate require the use of drug delivery systems to make it effective in the human body. Among various types of nanocarriers, block copolymer based ones are the most effective. These polymers are broadly used as drug-delivery systems, but the nature of this process is poorly understood. In this paper, we propose a molecular dynamics simulation study of the interaction of Curcumin with block copolymer based on polyethylene oxide (PEO) and polypropylene oxide (PPO). The study has been conducted considering the smallest PEO and PPO oligomers and multiple chains of the block copolymer Pluronic P85. Our study shows that the more hydrophobic 1,2-dimethoxypropane (DMP) molecules and PPO block preferentially coat the Curcumin molecule. In the case of the Pluronic P85, simulation shows formation of a drug-polymer aggregate within 50 ns. This process leaves exposed the PEO part of the polymers, resulting in better solvation and stability of the drug in water. PMID:23441964

  10. Nature Utilizes Unusual High London Dispersion Interactions for Compact Membranes Composed of Molecular Ladders.

    PubMed

    Wagner, J Philipp; Schreiner, Peter R

    2014-03-11

    London dispersion interactions play a key role in nature, in particular, in membranes that constitute natural barriers. Here we demonstrate that the spatial alignment of "molecular ladders" ([n]ladderanes), i.e., highly unusual and strained all-trans-fused cyclobutane moieties, leads to much larger attractive dispersion interactions as compared to alkyl chains of the same length. This provides a rationale for the occurrence of peculiar ladderane fatty acids in the dense cell walls of anammox bacteria. Despite the energetic penalty paid for the assembly of such strained polycycles, the advantage lies in significantly higher, dispersion-dominated interaction energies as compared to straight-chain hydrocarbon moieties commonly found in fatty acids. We discern the dispersion contributions to the total interaction energies using a variety of computational methods including modern dispersion-corrected density functional theory and high level ab initio approaches. Utilizing larger assemblies, we also show that the intermolecular interactions behave additively. PMID:26580198

  11. Nature of protein-CO2 interactions as elucidated via molecular dynamics.

    PubMed

    Drummond, Michael L; Wilson, Angela K; Cundari, Thomas R

    2012-09-27

    Rising global temperatures require innovative measures to reduce atmospheric concentrations of CO(2). The most successful carbon capture technology on Earth is the enzymatic capture of CO(2) and its sequestration in the form of glucose. Efforts to improve upon or mimic this naturally occurring process will require a rich understanding of protein-CO(2) interactions. Toward that end, extensive all-atom molecular dynamics (MD) simulations were performed on the CO(2)-utilizing enzyme phosphoenolpyruvate carboxykinase (PEPCK). Preliminary simulations were performed using implicit and explicit solvent models, which yielded similar results: arginine, lysine, tyrosine, and asparagine enhance the ability of a protein to bind carbon dioxide. Extensive explicit solvent simulations were performed for both wild-type PEPCK and five single-point PEPCK mutants, revealing three prevalent channels by which CO(2) enters (or exits) the active site cleft, as well as a fourth channel (observed only once), the existence of which can be rationalized in terms of the position of a key Arg residue. The strongest CO(2) binding sites in these simulations consist of appropriately positioned hydrogen bond donors and acceptors. Interactions between CO(2) and both Mn(2+) and Mg(2+) present in PEPCK are minimal due to the stable protein- and solvent-based coordination environments of these cations. His 232, suggested by X-ray crystallography as being a potential important CO(2) binding site, is indeed found to be particularly "CO(2)-philic" in these simulations. Finally, a recent mechanism, proposed on the basis of X-ray crystallography, for PEPCK active site lid closure is discussed in light of the MD trajectories. Overall, the results of this work will prove useful not only to scientists investigating PEPCK, but also to groups seeking to develop an environmentally benign, protein-based carbon capture, sequestration, and utilization system. PMID:22882078

  12. Investigation on the sucrose binding pocket of HIV-1 Integrase by molecular dynamics and synergy experiments.

    PubMed

    Tintori, Cristina; Esposito, Francesca; Morreale, Francesca; Martini, Riccardo; Tramontano, Enzo; Botta, Maurizio

    2015-08-01

    Enzymes whose catalytic activity depends on multimeric assembly are targets for inhibitors that perturb the interactions between the protein subunits such as the HIV-1 Integrase (IN). Sucrose has been recently crystallized in complex with IN revealing an allosteric binding pocket at the monomer-monomer interface. Herein, molecular dynamics were applied to theoretically test the effect of this small ligand on IN. As a result, such a compound increases the mutual free energy of binding between the two interacting monomers. Biological experiments confirmed the computational forecast. PMID:26048795

  13. Ab initio investigation of electronic properties of the magnesium hydride molecular ion.

    PubMed

    Khemiri, Noura; Dardouri, Riadh; Oujia, Brahim; Gadéa, Florent Xavier

    2013-09-12

    In this work, adiabatic potential energy curves, spectroscopic constants, dipole moments, and vibrational levels for numerous electronic states of magnesium hydride molecular ion (MgH(+)) are computed. These properties are determined by the use of an ab initio method involving a nonempirical pseudopotential for the magnesium core (Mg), the core polarization potential (CPP), the l-dependent cutoff functions and the full valence configuration interaction (FCI). The molecular ion is thus treated as a two-electron system. Our calculations on the MgH(+) molecular ion extend previous theoretical works to numerous electronic excited states in the various symmetries. A good agreement with the available theoretical and experimental works is obtained for the spectroscopic constants, the adiabatic potential energy curves, and the dipole moments for the lowest states of MgH(+). PMID:23944679

  14. Investigation on critical structural motifs of ligands for triggering glucocorticoid receptor nuclear migration through molecular docking simulations.

    PubMed

    Liu, Ya-Lin; Jang, Soonmin; Wang, Shih-Min; Chen, Chiu-Hao; Li, Feng-Yin

    2016-06-01

    The glucocorticoid receptor (GR), a transcription factor regulating gene expression in a ligand-dependent fashion, is known for flexibility in adapting various ligands with their structures ranging from steroid to non-steroid. However, in our previous study, GR shows a stringent discrimination against a set of steroid ligands with highly similar structures for triggering its nuclear migration. In order to resolve this puzzle, we employed molecular docking simulations to investigate the origin of this structural discrimination. By analyzing the docking orientations and the related ligand-GR interaction patterns, we found that the hydrophilicity mismatch between the docking ligand and the GR ligand-binding site is the main cause combined with the steric hindrance and structural rigidness of these steroid ligands. Furthermore, we utilized this knowledge to rationalize how the structure-binding interaction of non-steroid ligands triggers GR nuclear migration with their structures available in Protein Data Bank. PMID:26198481

  15. 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.

  16. A Preliminary Investigation of Affective Interaction in Chronic Pain Couples

    PubMed Central

    Johansen, Ayna Beate; Cano, Annmarie

    2007-01-01

    The objective of this preliminary study was to examine the extent to which affective marital interaction related to depressive symptoms in persons with chronic pain and their spouses and to pain severity in persons with pain. Couples from the community completed self-report surveys and engaged in a videotaped conversation on a topic of mutual disagreement that was coded for three affect types (i.e., anger/contempt, sadness, humor). Humor was positively related to marital satisfaction in both partners. Spouse anger/contempt and sadness were positively related to depressive symptoms in spouses. Several significant interaction effects between couple pain status (i.e., whether one or both partners reported pain) and affect also emerged. Specifically, sadness in the participant designated as the person with pain was associated with greater depressive symptoms and pain severity when only he or she reported pain whereas sadness was related to fewer depressive symptoms and less pain severity when both partners reported pain. The relationships between spouse anger and spouse depressive symptoms and between spouse humor and pain severity in the person with pain were also moderated by couple pain status. These exploratory findings can be interpreted in light of emotion regulation and pain empathy theories. For example, partners who have not experienced pain themselves may fail to empathize with persons in pain, thus preventing effective emotion regulation. When both spouses report chronic pain, expressions of negative affect may instead promote emotion regulation because the affect is experienced with a spouse who may be more empathetic. PMID:17521810

  17. Molecular docking simulation analysis of the interaction of dietary flavonols with heat shock protein 90

    PubMed Central

    Singh, Salam Pradeep; Deb, Chitta Ranjan; Ahmed, Sharif Ud