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Molecular Dynamics Methods (molecular + dynamics_methods)
Selected AbstractsThe embedded ion method: A new approach to the electrostatic description of crystal lattice effects in chemical shielding calculationsCONCEPTS IN MAGNETIC RESONANCE, Issue 5 2006Dirk Stueber Abstract The nuclear magnetic shielding anisotropy of NMR active nuclei is highly sensitive to the nuclear electronic environment. Hence, measurements of the nuclear magnetic shielding anisotropy represent a powerful tool in the elucidation of molecular structure for a wide variety of materials. Quantum mechanical ab initio nuclear magnetic shielding calculations effectively complement the experimental NMR data by revealing additional structural information. The accuracy and capacity of these calculations has been improved considerably in recent years. However, the inherent problem of the limitation in the size of the systems that may be studied due to the relatively demanding computational requirements largely remains. Accordingly, ab initio shielding calculations have been performed predominantly on isolated molecules, neglecting the molecular environment. This approach is sufficient for neutral nonpolar systems, but leads to serious errors in the shielding calculations on polar and ionic systems. Conducting ab initio shielding calculations on clusters of molecules (i.e., including the nearest neighbor interactions) has improved the accuracy of the calculations in many cases. Other methods of simulating crystal lattice effects in shielding calculations that have been developed include the electrostatic representation of the crystal lattice using point charge arrays, full ab initio methods, ab initio methods under periodic boundary conditions, and hybrid ab initio/molecular dynamics methods. The embedded ion method (EIM) discussed here follows the electrostatic approach. The method mimics the intermolecular and interionic interactions experienced by a subject molecule or cluster in a given crystal in quantum mechanical shielding calculations with a large finite, periodic, and self-consistent array of point charges. The point charge arrays in the EIM are generated using the Ewald summation method and embed the molecule or ion of interest for which the ab initio shielding calculations are performed. The accuracy with which the EIM reproduces experimental nuclear magnetic shift tensor principal values, the sensitivity of the EIM to the parameters defining the point charge arrays, as well as the strengths and limitations of the EIM in comparison with other methods that include crystal lattice effects in chemical shielding calculations, are presented. © 2006 Wiley Periodicals, Inc. Concepts Magn Reson Part A 28A: 347,368, 2006 [source] Interpretation of biological activity data of bacterial endotoxins by simple molecular models of mechanism of actionFEBS JOURNAL, Issue 3 2000Vladimir Frecer Lipid A moiety has been identified as the bioactive component of bacterial endotoxins (lipopolysaccharides). However, the molecular mechanism of biological activity of lipid A is still not fully understood. This paper contributes to understanding of the molecular mechanism of action of bacterial endotoxins by comparing molecular modelling results for two possible mechanisms with the underlying experimental data. Mechanisms of action involving specific binding of lipid A to a protein receptor as well as nonspecific intercalation into phospholipid membrane of a host cell were modelled and analysed. As the cellular receptor for endotoxin has not been identified, a model of a peptidic pseudoreceptor was proposed, based on molecular structure, symmetry of the lipid A moiety and the observed character of endotoxin-binding sites in proteins. We have studied the monomeric form of lipid A from Escherichia coli and its seven synthetic analogues with varying numbers of phosphate groups and correlated them with known biological activities determined by the Limulus assay. Gibbs free energies associated with the interaction of lipid A with the pseudoreceptor model and intercalation into phospholipid membrane calculated by molecular mechanics and molecular dynamics methods were used to compare the two possible mechanisms of action. The results suggest that specific binding of lipid A analogues to the peptidic pseudoreceptor carrying an amphipathic cationic binding pattern BHPHB (B, basic; H, hydrophobic; P, polar residue, respectively) is energetically more favourable than intercalation into the phospholipid membrane. In addition, binding affinities of lipid A analogues to the best minimum binding sequence KFSFK of the pseudoreceptor correlated with the experimental Limulus activity parameter. This correlation enabled us to rationalize the observed relationship between the number and position of the phosphate groups in the lipid A moiety and its biological activity in terms of specific ligand,receptor interactions. If lipid A,receptor interaction involves formation of phosphate-ammonium ion-pair(s) with cationic amino-acid residues, the specific mechanism of action was fully consistent with the underlying experimental data. As a consequence, recognition of lipid A variants by an amphipathic binding sequence BHPHB of a host-cell protein receptor might represent the initial and/or rate-determining molecular event of the mechanism of action of lipid A (or endotoxin). The insight into the molecular mechanism of action and the structure of the lipid A-binding pattern have potential implications for rational drug design strategies of endotoxin-neutralizing agents or binding factors. [source] Free energy and structure of polyproline peptides: An ab initio and classical molecular dynamics investigationINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 15 2010Mahmoud Moradi Abstract Depending on their environment, polyproline peptides form chiral helices that may be either left- (PPII) or right-handed (PPI). Here, we have characterized both the structure and free energy landscapes of Ace-(Pro)n -Nme (n an integer less than 13) peptides, in vacuo and in implicit water environments. Both ab initio and classical molecular dynamics methods were used. In terms of the latter, we used a recently developed Adaptively Biased Molecular Dynamics (ABMD) method in conjunction with three different force fields (ff99, ff99SB, ff03) and two different Generalized Born models for the implicit solvent environment. Specifically, the ABMD method provides for an accurate description of the free energy landscapes in terms of a set of collective variables, which were carefully chosen as to reflect the "slow modes" of the polyproline peptides. These are primarily based on the cis - trans isomerization associated with the prolyl bonds. In agreement with recent experimental results, the peptides form not only the pure PPII or PPI structures but also a large number of stable conformers having more or less similar free energies, whose distributions we have characterized. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010 [source] Conformation of N-terminal HIV-1 tat (fragment 1,9) peptide by NMR and MD simulationsJOURNAL OF PEPTIDE SCIENCE, Issue 11 2001Meena Kanyalkar Abstract The N -terminal portion of HIV-1 Tat covering residues 1,9 is a competitive inhibitor of dipeptidyl peptidase IV (DP IV). We have used 1H NMR techniques, coupled with molecular dynamics methods, to determine the conformation of this peptide in the three diverse media: DMSO-d6, water (pH 2.7) and 40% HFA solution. The results indicate that in both DMSO-d6 and HFA the peptide has a tendency to acquire a type I ,-turn around the segment Asp5 -Pro6 -Asn7 -Ile8. The N -terminal end is seen to be as a random coil. In water, the structure is best described as a left-handed polyproline type II (PPII) helix for the mid segment region Asp2 to Pro6. The structures obtained in this study have been compared with an earlier report on Tat (1,9). Copyright © 2000 European Peptide Society and John Wiley & Sons, Ltd. [source] Transmission electron microscopy and theoretical analysis of AuCu nanoparticles: Atomic distribution and dynamic behaviorMICROSCOPY RESEARCH AND TECHNIQUE, Issue 7 2006J.A. Ascencio Abstract Though the application of bimetallic nanoparticles is becoming increasingly important, the local atomistic structure of such alloyed particles, which is critical for tailoring their properties, is not yet very clearly understood. In this work, we present detailed study on the atomistic structure of Au,Cu nanoparticles so as to determine their most stable configurations and the conditions for obtaining clusters of different structural variants. The dynamic behavior of these nanoparticles upon local heating is investigated. AuCu nanoparticles are characterized by high resolution transmission electron microscopy (HRTEM) and energy filtering elemental composition mapping (EFECM), which allowed us to study the internal structure and the elemental distribution in the particles. Quantum mechanical approaches and classic molecular dynamics methods are applied to model the structure and to determine the lowest energy configurations, the corresponding electronic structures, and understand structural transition of clusters upon heating, supported by experimental evidences. Our theoretical results demonstrate only the core/shell bimetallic structure have negative heat of formation, both for decahedra and octahedral, and energetically favoring core/shell structure is with Au covering the core of Cu, whose reverse core/shell structure is not stable and may transform back at a certain temperature. Experimental evidences corroborate these structures and their structural changes upon heating, demonstrating the possibility to manipulate the structure of such bimetallic nanoparticles using extra stimulating energy, which is in accordance with the calculated coherence energy proportions between the different configurations. Microsc. Res. Tech., 2006. © 2006 Wiley-Liss, Inc. [source] Molecular Dynamics Simulations of Polymer-Bonded Explosives (PBXs): Modeling, Mechanical Properties and their Dependence on Temperatures and Concentrations of BindersPROPELLANTS, EXPLOSIVES, PYROTECHNICS, Issue 5 2007Jijun Xiao Abstract Two models, i.e. "covering" and "cutting" models, for the polymer-bonded explosives (PBXs) were proposed for different researching aspects. Used for choosing polymeric binders, the "covering" models are mainly applied to find the relations of temperatures and concentrations respectively with elastic properties of the PBXs. The "cutting" model is especially used to describe the highly anisotropic behavior of 1,3,5-triamino-2,4,6-trinitrobenzene crystals (TATB). These models were realized by using molecular dynamics methods. It is found that the ductility of crystalline TATB can be effectively improved by blending fluorine-containing polymers in small amounts. The moduli for the PBXs decrease with increase in temperature and concentration of binders. Different crystalline surfaces interacting with the same polymer binder have different modulus-decreasing effects due to the highly anisotropic behavior of TATB. The modulus-decreasing effect for different crystalline surfaces ranking order is (010),(100)>(001). [source] Solution Structure and Stability of Tryptophan-Containing Nucleopeptide DuplexesCHEMBIOCHEM, Issue 1 2003Irene Gómez-Pinto Abstract Covalently linked peptide,oligonucleotide hybrids were used as models for studying tryptophan,DNA interactions. The structure and stability of several hybrids in which peptides and oligonucleotides are linked through a phosphodiester bond between the hydroxy group of a homoserine (Hse) side chain and the 3,-end of the oligonucleotide, have been studied by both NMR and CD spectroscopy and by restrained molecular dynamics methods. The three-dimensional solution structure of the complex between Ac-Lys-Trp-Lys-Hse(p3,dGCATCG)-Ala-OH (p=phosphate, Ac=acetyl) and its complementary strand 5,dCGTAGC has been determined from a set of 276 experimental NOE distances and 33 dihedral angle constraints. The oligonucleotide structure is a well-defined duplex that belongs to the B-form family of DNA structures. The covalently linked peptide adopts a folded structure in which the tryptophan side chain stacks against the 3,-terminal guanine moiety, which forms a cap at the end of the duplex. This stacking interaction, which resembles other tryptophan,nucleobase interactions observed in some protein,DNA complexes, is not observed in the single-stranded form of Ac-Lys-Trp-Lys-Hse(p3,dGCATCG)-Ala-OH, where the peptide chain is completely disordered. A comparison with the pure DNA duplex, d(5,GCTACG3,),(5,CGTAGC3,), indicates that the interaction between the peptide and the DNA contributes to the stability of the nucleopeptide duplex. The different contributions that stabilize this complex have been evaluated by studying other nucleopeptide compounds with related sequences. [source] Conformational analysis of endomorphin-1 by molecular dynamics methodsCHEMICAL BIOLOGY & DRUG DESIGN, Issue 4 2003B. Leitgeb Abstract: Endomorphin-1 (EM1, H-Tyr-Pro-Trp-Phe-NH2) is a highly potent and selective agonist for the ,-opioid receptor. A conformational analysis of this tetrapeptide was carried out by simulated annealing and molecular dynamics methods. EM1 was modeled in the neutral (NH2 -) and cationic (NH -) forms of the N-terminal amino group. The results of NMR measurements were utilized to perform simulations with restrained cis and trans Tyr1 -Pro2 peptide bonds. Preferred conformational regions in the ,2,,2, ,3,,3 and ,4,,4 Ramachandran plots were identified. The g(+), g(,) and trans rotamer populations of the side-chains of the Tyr1, Trp3 and Phe4 residues were determined in ,1 space. The distances between the N-terminal N atom and the other backbone N and O atoms, and the distances between the centers of the aromatic side-chain rings and the Pro2 ring were measured. The preferred secondary structures were determined as different types of , -turns and , -turns. In the conformers of trans -EM1, an inverse , -turn can be formed in the N-terminal region, but in the conformers of cis -EM1 the N-terminal inverse , -turn is absent. Regular and inverse , -turns were observed in the C-terminal region in both isomers. These , - and , -turns were stabilized by intramolecular H-bonds and bifurcated H-bonds. [source] | |||||||||||||