Toward the supramolecular structure of collagen: a molecular dynamics approach

The structure, stability, and conformational dynamics of an assembly of two pentameric bundles made of collagen-like triple helical segments are explored using 1.2 ns molecular dynamics simulations in three environments: 8.0% (v/v) formaldehyde/water solution, 1.4% (v/v) gallic acid/water solution, and pure water. Stable supramolecular arrangements, where the two collagen units are very close to each other at interacting distances, are identified via docking and energy minimization procedures. Analysis of the interaction with formaldehyde and gallic acid suggests that they perturb the protein in a similar way depending on hydrogen-bonding capability, hydrophobic association properties, and the size and concentration of the compound.     

Adsorption of collagen onto single walled carbon nanotubes: a molecular dynamics investigation

Classical molecular dynamics (MD) simulation has been carried out to understand the adsorption of collagen like peptides onto single walled carbon nanotubes (CNT) in an aqueous environment. It is observed that the triple helical structure of all the model collagen like peptides (CPs) has been unaltered upon adsorption onto CNT. The model CPs do not wrap around the CNT, however, the axis of the triple helix subtends a cross angle with respect to the axis of the CNT. The interaction between the CPs and CNT as well as that between the CPs and water molecules was observed by MD simulation snapshots. The inherent nature of the interaction of CPs with CNT facilitates the penetration of CPs into the water/CNT interface. During this process, water molecules trapped between the CPs and CNT are appreciably displaced. Although, hydrophobic-hydrophobic interaction is crucial for the interaction, the role of πR (R = OH and NH(2)) interactions are also observed from the geometrical parameters. The sequence specific interaction of CPs with CNT is evident from the results. It is found that the length of the CNT, curvature of the CNT and length of the CPs do not significantly influence interaction between the two systems. Overall the findings provide important information for the development of nanocomposite materials from collagen and CNT.     

Role of ions on structure and stability of a synthetic gramicidin ion channel in solution. A molecular dynamics study

We performed a molecular dynamics (MD) simulation to the investigate structure and stability of a synthetic gramicidin-like peptide in solution with and without ions. The starting structures of the MD simulations were taken from two recently solved NMR structures of this peptide in isotropic solution, which forms stable monomers or dimers in the presence or absence of ions, respectively. The monomeric structure is channel-like and is assumed to be stabilized by the presence of two Cs(+) ions bound in the channel, each one close to one channel entrance. In our MD simulations, we observed how the Cs(+) ions bind in the channel formed by the monomeric gramicidin-like peptide using implicit solvent and explicit ions with a concentration of 2 M. MD simulations were performed with and without explicit ions but with an implicit solvent model defined by the generalized Born approximation, which was used to mimic the dielectric properties of the solvent and to speed up the computations.     

A molecular dynamics study of Lys-Trp-Lys: structure and dynamics in solution following photoexcitation

We report studies of the structure and dynamics of a tripeptide Lys-Trp-Lys (KWK) in aqueous solution following photoexcitation by molecular dynamics simulations. For ground-state KWK, we observe three stable conformations with free energy differences of less than 5.2 kJ/mol. Each conformer is stabilized by a pi-cation interaction between one of three protonated amino groups and the indole moiety. For the excited state of tryptophan in KWK, the simulated molecular dynamics of the three isomers are similar, all in good agreement with recent femtosecond experiments (J. Phys. Chem. B 2005, 109, 16901). Specifically, we observe: (1) the fluorescence anisotropy is dominated by a single-exponential component and decays in approximately 130 ps, (2) the total dynamic Stokes shift reaches approximately 2700 cm(-1), and (3) the excited state relaxation dynamics occurs on several time scales ranging from femtoseconds to tens of picoseconds. The relaxation dynamics involve rapid initial response of neighboring water, followed by local motions of flexible peptide chains. These processes drive global restructuring of the tripeptide on a rather flat energy surface, inducing slower dynamics evident in both the water and protein contributions to the stabilization energy of the photoexcited chromophore. The water and protein dynamics are strongly correlated. On a still longer time scale, we observe isomerization of two excited state conformers to the other most stable one, an analogue for evolution of trajectories along the funnel on the rugged free energy landscape to the final "native" state. Our studies suggest new experiments to detect this unique dynamics.     

Role of solvents in stability of collagen

The influence of hydroxymethyl chain length of the solvents on collagen was established with conformational stability and thermal stability. Thermal stability of monomeric collagen and RTT fibres (rat tail tendon) treated with methanol, ethylene glycol (EG) and glycerol were reported using the melting temperature for helix-coil transition and the peak temperature for collagen-gelatin transition. Both melting temperature and peak temperature increases as the hydroxymethyl chain length increases. Conformational stability of collagen solution treated with lower and higher concentrations of methanol, ethylene glycol and glycerol indicates that aggregation of collagen molecule is more at higher concentrations of these solvents. The concentration dependence is greater for the increased number of OH groups. Since protein aggregation is associated with neuro degenerative diseases, aggregation of collagen molecule in the presence of solvents is of great importance for biomedical application.     

Atomic detail investigation of the structure and dynamics of DNA.RNA hybrids: a molecular dynamics study

DNA.RNA hybrid duplexes are biologically important molecules and are shown to have potential therapeutic properties. To investigate the relationship between structures, energetics, solvation and RNase H activity of hybrid duplexes in comparison with pure DNA and RNA duplexes, a molecular dynamics study using the CHARMM27 force field was undertaken. The structural properties of all four nucleic acids considered are in very good agreement with the experimental data. The backbone dihedral angles and the puckering of the (deoxy)ribose indicate that the purine rich strands retain their A-/B-like properties but the pyrimidine rich DNA strand undergoes A-B conformational transitions. The minor groove widths of the hybrid structures are narrower than those in the RNA duplex, a requirement for RNase H binding. In addition, sampling of noncanonical phosphodiester backbone dihedrals by the DNA strands, differential solvation properties and helical properties, most notably rise, are suggested to contribute to hybrids being RNase H substrates. Differential RNase H activity toward hybrids containing purine versus pyrimidine rich RNA strands is suggested to be due to sampling of values of the phosphodiester backbone dihedrals in the DNA strands. Notably, the present results indicate that hybrids have decreased flexibility as compared to RNA, in contrast to previous reports.     

阿魏酸分子结构和振动光谱的理论研究

阿魏酸是一种有效的天然油脂抗氧化剂.采用密度泛函理论(DFT) B3LYP方法和从头算HF两种方法,在6-311++G**基组水平上对阿魏酸分子的几何结构进行全优化,得到其几何结构参数,进一步计算得到阿魏酸的红外和拉曼振动光谱.计算结果表明,采用B3LYP和HF 2种方法优化得到的几何结构及频率值是一致的,对在B3LYP方法下计算得到的红外和拉曼振动频率进行合理的理论归属并与SDBS数据库实验数据进行比较,发现计算得到的红外和拉曼振动频率与实验测定结果符合较好.阿魏酸分子结构和振动光谱的研究,为研究阿魏酸及其衍生物的化学结构与生理活性之间的构效关系提供依据.     

A molecular dynamics study of nitric oxide in water: diffusion and structure

We present molecular dynamics simulations of the diffusion coefficients and structure of water-nitric oxide mixtures at ambient (298 K) and in vivo (310 K) conditions. A two-site rigid-body molecular model with partial charges and a Lennard-Jones potential on both sites is proposed for nitric oxide and used in conjunction with the extended simple point-charge model for liquid water in our simulations. The diffusion coefficients obtained from the simulations are in good agreement with experimental data. The results from intermolecular partial pair functions show that under these thermodynamic conditions, the existence of nitric oxide in liquid water has little impact on the structure of water and the tendency to form H bonds between water molecules. We also find that it is unlikely that H bonds form between the hydrogen atoms in water and either the nitrogen or the oxygen atom on the nitric oxide at the temperatures and densities examined in this study. This study suggests that in low concentrations nitric oxide molecules exist as free molecules in liquid water rather than forming complexes with water molecules.     

Stereospecific morphogenesis of aspartic acid helical crystals through molecular recognition

Helical morphologies were generated from aspartic acid (Asp) crystals in agar gel matrix. The morphogenesis stereospecifically proceeded in the helical crystal growth: D- and L-Asp provided left- and right-handed structures, respectively. The backbone of the helical morphology was twisted twins of tilted unit crystals, as was the case with inorganic helical crystals. The molecular recognition between the Asp crystals and agar matrix molecules resulted in the stereospecific morphogenesis. The chirality in Asp and agar molecules, the enantiomorph of unit crystals, and the resultant macroscopic helix were exquisitely associated with each other.     

A molecular dynamics investigation of hydrolytic polymerization in a metal-hydroxide gel

The early stages of the spontaneous hydrolytic polymerization of an active hydroxide in the anti-bayerite structure are followed by using molecular dynamics simulations. The polymer populations are calculated as a function of reaction progress and compared with a model governed by purely random bonding. In agreement with experimental observations in aqueous solutions, the transformation of singly bridged to doubly bridged metal ions is shown to have a significant autocatalytic component. The overall polymer populations, however, are very close to the predictions of the random bonding model, indicating that local autocatalytic behavior is decoupled from multimer populations at the larger scales. The calculations show that solid-state transformation processes do not preferentially give rise to higher order multimers, and suggest that interfacial processes, involving bulk solution, are required to facilitate rapid transformation to higher order oligomers. Two reaction pathways are identified for the dewatering of mu-H(3)O(2) bridges into mu-OH bridges. Both are activated primarily by undercoordination of one of the metals centers involved in the bridge.     

Temperature effects on the structure and dynamics of liquid dimethyl sulfoxide: A molecular dynamics study

The molecular dynamics (MD) simulation technique has been employed to investigate the thermodynamic properties and transport coefficients of the neat liquid dimethyl sulfoxide (DMSO). The fluid has been studied at temperatures in the range 298–353 K and at a pressure equal to 1 atm. The simulations employed a nine-site potential model, which is presented for the first time here, and all the available non-polarizable models. The performance of each model is tested using the same statistical mechanical ensemble and simulation method under the same conditions, revealing its weaknesses and strengths. Thermodynamic properties, microscopic structure and dynamic properties, such as transport coefficients, rotational and single-dipole correlation times have been calculated and compared with available experimental results. Estimations of transport coefficients from various theoretical and empirical models are tested against experimental and MD results. Translational and rotational dynamics suggest the existence of the cage effect and agree with the Stokes–Einstein–Debye relation. The dipole relaxation times calculated are discussed in terms of simple and useful approximations, such as the Glarum–Powles and Fatuzzo–Mason models.     

Mechanism of bleomycin suicide: a Car-Parrinello molecular dynamics investigation

Using first-principles molecular dynamics simulations (Car-Parrinello method) we investigated the possible reaction pathways for decay of the active bleomycin-Fe(III)-OOH complex, so-called bleomycin suicide. The theoretical model of activated bleomycin contains the whole metal bonding domain of the bleomycin ligand. Simulations performed both in a vacuum and in water show that a facile decaying process involves a homolytic O-O bond cleavage with an almost simultaneous hydrogen atom abstraction. The formation of an intra- or intermolecular hydrogen bond appears to be crucial for the decay of the activated bleomycin. We did not observe any evidence of heterolytic cleavage of the O-O bond of the Fe(III)-OOH species.     

Supercritical ammonia: a molecular dynamics simulation and vibrational spectroscopic investigation

Combining infrared spectroscopy and molecular dynamics simulations, we have investigated the structural and dynamical properties of ammonia from liquid state (T = 220 and 303 K) up to the supercritical domain along the isotherm T = 423 K. Infrared spectra show that the N-H stretching and bending modes are significantly perturbed which is interpreted as a signature of the change of the local environment. In order to compare the experimental spectra with those obtained using molecular dynamics simulation, we have used a flexible four sites model which allows to take into account the anharmonicity in all the vibration modes particularly that of the inversion mode of the molecule. A good agreement between our experimental and calculated spectra has been obtained hence validating the intermolecular potential used in this study to simulate supercritical ammonia. The detailed analysis of the molecular dynamics simulation results provides a quantitative insight of the relative importance of hydrogen bonding versus nonhydrogen bonded interactions that governs the structure of fluid ammonia.     

Full-atom molecular dynamics study of structure and stability of filament-like aggregates formed by silver mercaptide molecules

The process of the emergence of gel network in a cystein-silver solution is studied by full-atom molecular dynamics. It is shown that, because of the formation of donor-acceptor sulfur-silver bonds, clusters are formed by zwitterions and cations of silver mercaptide followed by the formation of filament-like aggregates. The analysis of formed molecular configurations demonstrates that filament-like aggregates are stabilized by virtue of the interaction between ?NH ₃ ⁺ and ?C(O)O^? groups that belong to the particles of silver mercaptide comprising neighbor clusters. The absorption UV spectra of various aggregates formed from particles of silver mercaptide are investigated by the quantum-mechanical ZINDO/1 method.     

Discovery of potential inhibitor against human acetylcholinesterase: a molecular docking and molecular dynamics investigation

Alzheimer’s disease (AD) is a progressive neurodegenerative disease of central nervous system among elderly people. Human acetylcholinesterase (hAChE), an important enzyme in neuronal signaling, is responsible for the degradation of acetylcholine which in turn prevents the post synaptic signal transmissions. hAChE has been an attractive target of drug discovery for the search of therapeutics against AD. In the recent past hAChE has become hot target for the investigation of new potential therapeutics. We performed virtual screening of entire database against hAChE. Further, the extra precision molecular docking was carried out to refine the docking results and the best complex was passed for molecular dynamics simulations in order of understanding the hAChE dynamics and its behavior in complex with the ligand which corroborate the outcomes of virtual screening. This also provides binding free energy data that establishes the ligands efficiency for inhibiting hAChE. The computational findings discussed in this paper provide initial information of inhibitory effects of ligand, (drugbank entry DB00983), over hAChE.     

Relation between amorphous structure of polymers and penetrant diffusion: A molecular dynamics simulation

Molecular dynamics simulation has been performed for studying the relation between amorphous structure of polymers and penetrant diffusion. The self-diffusion coefficients of O₂ and He in various polymer models, which differ from each other in view of the amorphous structure, were calculated above their glass transition temperatures. The amorphous structure was characterized by considering the percolation of the unoccupied volume. A good correlation was found between the self-diffusion coefficients and the number of clusters in the unoccupied volume at the critical point of the percolation. Based on the simulated cluster size distribution at the critical point, we defined a parameter into which effects of both the amorphous structure and the penetrant size are well incorporated. It was confirmed that the penetrant diffusion is intimately associated with the amorphous structure of polymers.     

n-Heptane under pressure: structure and dynamics from molecular simulations

Atomistic molecular dynamics simulations have been performed in the isothermal-isobaric ensemble to explore the phase behavior of n-heptane. Motivated by recent high-pressure spectroscopic experiments on n-heptane, the present work aims at understanding the liquid-solid and the alluded to solid-solid transitions upon increasing pressure. Starting from the stabilized solid phase at 300 K and 10 kbar, we have investigated the range of these two transitions by a gradual decrease and increase of pressure, respectively. Although the solid-liquid transition has clear signatures such as the formation of gauche defects along the molecular backbone, the present model does not show any sign of a first-order solid-solid transition at high pressures. However, interesting changes in the environment around methyl groups and in their dynamics are observed. These have been substantiated by calculations of the vibrational density of states obtained from a normal-mode analysis and from the simulation trajectory.     

The equivalent potential of water for electronic structure of aspartic acid

The equivalent potential of water for the electronic structure of aspartic acid (Asp(-)) in solution is constructed by the first-principles, all-electrons, ab initio calculations. Aspartic acid is a hydrophilic amino acid which is negatively charged in neutral water solution. The main process of calculation consists of three steps. Firstly, the geometric structure of the cluster containing Asp(-) and water molecules is calculated by the free cluster calculation. Then, based on the obtained geometric structure, the electronic structure of Asp(-) with the potential of water molecules is calculated using the self-consistent cluster-embedding method. Finally, the electronic structure of Asp(-) with the potential of dipoles is calculated. The results show that the major effect of water on Asp(-)'s electronic structure is lowering the occupied molecular orbitals by about 0.02 Ry on average, and narrowing energy gap by 10.8%. The effect of water on the electronic structure of Asp(-) can be simulated by dipoles potential.     

Molecular dynamics simulations of structure and dynamics of organic molecular crystals

A set of model compounds covering a range of polarity and flexibility have been simulated using GAFF, CHARMM22, OPLS and MM3 force fields to examine how well classical molecular dynamics simulations can reproduce structural and dynamic aspects of organic molecular crystals. Molecular structure, crystal structure and thermal motion, including molecular reorientations and internal rotations, found from the simulations have been compared between force fields and with experimental data. The MM3 force field does not perform well in condensed phase simulations, while GAFF, CHARMM and OPLS perform very similarly. Generally molecular and crystal structure are reproduced well, with a few exceptions. The atomic displacement parameters (ADPs) are mostly underestimated in the simulations with a relative error of up to 70%. Examples of molecular reorientation and internal rotation, observed in the simulations, include in-plane reorientations of benzene, methyl rotations in alanine, decane, isopropylcyclohexane, pyramidal inversion of nitrogen in amino group and rotation of the whole group around the C-N bond. Frequencies of such dynamic processes were calculated, as well as thermodynamic properties for reorientations in benzene and alanine. We conclude that MD simulations can be used for qualitative analysis, while quantitative results should be taken with caution. It is important to compare the outcomes from simulations with as many experimental quantities as available before using them to study or quantify crystal properties not available from experiment.