Molecular Dynamics Investigation of Bond Ordering of Unsaturated Lipids in Monolayers

Molecular dynamics simulations of three model lipid monolayers of 2,3-diacyl-D-glycerolipids, that contained stearoyl (18:0) in the position 3 and oleoyl (18:9cis), linoleoyl (18:26cis), or linolenoyl (18:33cis) in the position 2, have been carried out. The simulation systems consisted of 24 lipid molecules arranged in a rectangular simulation cell, with periodic boundary conditions in the surface plane. 1 nanosecond simulations were performed at T = 295 K. C-C and C-H bond order parameter profiles and the bond orientation distributions about the monolayer normal have been calculated. The relation of the distributions to the order parameters was analyzed in terms of maxima and widths of the distributions. The cis double bond order parameter is found to be higher than those of adjacent single C-C bonds. The widths of the two distributions of C-H bonds of the cis double bond segment in di- and triunsaturated molecules are much smaller than that obtained for methylene group located between the double bonds. The bond orientation distribution function widths depend on both the segment location in the chain and the segment chemical structure.     

A Molecular Dynamics Investigation of Chain Conformational Changes In Compressed Bilayers

Abstract

The conformations of the chains constituting the hydrophilic component of alkyl monolayers and bilayers are investigated by performing molecular dynamics atomistic simulations on these systems at different temperatures. Several monitoring techniques are used to reveal the chain conformations, including atom pair radial distribution functions, evolutions of the torsional angles over thousands of timesteps, frequency distributions of the torsionl angles and ‘snapshot’ plots of the atomic configurations. These methods consistently testify to the stability of the trans (fully extended) character of the strain-free alkyl chains up to room temperature. The chains retain much of this conformation even when the layers are compressed by the application of pressure, to which the chains respond by ‘folding’ at the ends attaching them to the substrate planes while maintaining directions which are mainly normal to these planes. A non-zero gap between the layers is also maintained. A pressure of about 50 kbar abruptly causes all motion in the chains to cease, resulting in a highly ordered lattice structure.     

Molecular Dynamics Simulation of Hexamine and Suberic Acid

In order to perform a molecular dynamics (MD) simulation of the incommensurate crystalline structure hexamethylenetetramine suberate (C 6 H 12 N 4 )(HOOC-(CH 2 ) 6 -COOH), we present in a first step the separate simulations of the crystalline structure of each of the two pure components, hexamethylenetetramine (HMT) and suberic acid. The domain decomposition parallel MD program ddgmq is used for this purpose. A second-generation consistent force field (CFF91) is employed to describe the interactions between atoms. Starting from experimental crystal structures, both pure components were heated from low to high temperatures. Our MD results show that the HMT system can be well represented by CFF91. In the case of suberic acid the layered structure of the crystal is largely preserved although deviations in the unit cell lengths from the experimental values are ～10%. Rather than attempt a complex re-parametrisation of CFF91 we chose to impose a fixed compensating external pressure tensor to correct for the deficiencies of the chosen force field. After optimising this compensating external pressure tensor at one temperature we find that experimental lattice constants and angles can be well reproduced over a range of temperatures.     

A Molecular Dynamics Simulation of an Aqueous Beryllium Chloride Solution

Abstract

A Molecular Dynamics simulation of a 1.1 molal aqueous BeCl₂ solution was performed with the flexible BJH model for water and a newly developed three-body potential for Be²⁺ -H₂O interactions derived from ab-initio calculations. The properties of the potential are discussed and radial distribution functions, angular distributions and dynamic properties of the solution like vibrational modes and hindered rotations are analyzed.     

Theoretical Investigation on the Binding Specificity of Sialyldisaccharides with Hemagglutinins of Influenza A Virus by Molecular Dynamics Simulations

Recognition of cell-surface sialyldisaccharides by influenza A hemagglutinin (HA) triggers the infection process of influenza. The changes in glycosidic torsional linkage and the receptor conformations may alter the binding specificity of HAs to the sialylglycans. In this study, 10-ns molecular dynamics simulations were carried out to examine the structural and dynamic behavior of the HAs bound with sialyldisaccharides Neu5Acα(2–3)Gal (N23G) and Neu5Acα(2–6)Gal (N26G). The analysis of the glycosidic torsional angles and the pair interaction energy between the receptor and the interacting residues of the binding site reveal that N23G has two binding modes for H1 and H5 and a single binding mode for H3 and H9. For N26G, H1 and H3 has two binding modes, and H5 and H9 has a single binding mode. The direct and water-mediated hydrogen bonding interactions between the receptors and HAs play dominant roles in the structural stabilization of the complexes. It is concluded from pair interaction energy and Molecular Mechanic-Poisson-Boltzmann Surface Area calculations that N26G is a better receptor for H1 when compared with N23G. N23G is a better receptor for H5 when compared with N26G. However, H3 and H9 can recognize N23G and N26G in equal binding specificity due to the marginal energy difference (≈2.5 kcal/mol). The order of binding specificity of N23G is H3 > H5 > H9 > H1 and N26G is H1 > H3 > H5 > H9, respectively. The proposed conformational models will be helpful in designing inhibitors for influenza virus.     

A Comparative Molecular Dynamics Study of Thermophilic and Mesophilic Ribonuclease HI Enzymes

Abstract

We studied a pair of homologous thermophilic and mesophilic ribonuclease HI enzymes by molecular dynamics simulations. Each protein was subjected to three 5 ns simulations in explicit water at both 310 K and 340 K. The thermophilic enzyme showed larger overall positional fluctuations at both temperatures, while only the mesophilic enzyme at the higher temperature showed significant instability. When the temperature is changed, the relative flexibility of different local segments on the two proteins changed differently. Principal component analysis showed that the simulations of the two proteins explored largely overlapping regions in the conformational space. However, at 340 K, the collective structure variations of the thermophilic protein are different from those of the mesophilic protein. Our results, although not in accordance with the view that hyperthermostability of proteins may originate from their conformational rigidity, are consistent with several recent experimental and simulation studies which showed that thermophilic proteins may be conformationally more flexible than their mesophilic counterparts. The decorrelation between conformational rigidity and hyperthermostability may be attributed to the temperature dependence and long range nature of electrostatic interactions that play more important roles in the structural stability of thermophilic proteins.     

Ewald Summation in the Molecular Dynamics Simulation of Large Ionic Systems

Abstract

The accuracy and efficiency of the direct Ewald summation are discussed in terms of the size of a Molecular Dynamics (MD) ionic system and the ranges of the r-space and q-space summations. The dependence of the convergence parameter α on the size of the system and on the choice of cut-off radius for the short-range potential is given. The possibility of neglecting the q-space term for large ionic systems is discussed in terms of the accuracy and efficiency of the simulation.     

Molecular Dynamics Simulations for Metallic Nanosystems

Nanotechnology is a crucial field for future scientific development where many different disciplines meet. Computational modelization of nanometer-sized structures is a key issue in this development because (i) it allows a considerable saving of resources and costly experimental setups intended to fabricate nanometric test devices and (ii) nowadays the study of nanometric sized systems is feasible with thoroughly designed computational codes and relatively low cost computational resources. This article describes how molecular dynamics simulations, in combination with potentials obtained in the framework of the embedded atom method, are able to describe the properties of two systems of interest for the development of future nanoelectronic devices: metallic nanowires and metallic nanofilms. Our results show that nanowire stretching results in a series of well-defined geometric structures (shells) and that thin films experiment a crystallographic phase transition for a decreasing number of layers. In both cases, good agreement with experiments is found.     

Elastic Properties of Zinc-blende G a N,A l N and I n N from Molecular Dynamics

Molecular dynamics calculations of the adiabatic elastic constants of group III-Nitrides for temperatures ranging from 300 to 900 K have been performed. The results show good agreement with first-principles calculations. The moduli decreased with increasing temperature. The structural properties of zinc-blende GaN, AlN and InN are reported. Good agreement between the calculated and experimental values of the lattice constant, the cohesion energy, and the bulk modulus and its derivative are obtained.     

Molecular Dynamics Simulation of Collective Motions in Binary Liquids

Collective dynamic properties of different kind of binary liquid mixtures have been investigated by molecular dynamics simulation. The study includes both the longitudinal and the transverse current spectra in simple liquid alloys, 1:1 molten salts and liquid binary mixtures of neutral particles with an ionic-like structure. These systems were chosen as representative of binary liquids with different static structures in order to analyse the effects of structural ordering on the mechanisms of dynamic collective properties. The effect of the mass asymmetry between the two species in the mixture has been also discussed from the results for two different mass ratios for each kind of structure. Two length scales have been considered. On the one hand, the hydrodynamic scale (low wave numbers), where the modes for the partial currents of the two species are characterised by very close frequencies. On the other hand, the molecular scale (higher wave numbers), where the characteristic frequencies for the two species show noticeable differences. Vibrational concentration current modes (optic modes) have been found in neutral mixtures though their influence is rather weak, being the collective dynamic properties of this kind of systems dominated by the mass current modes (acoustic modes). On the contrary, in mixtures of charged particles such as molten salts the contribution of the concentration (charge) currents to the collective dynamics is important and optic modes can be characterised by a well-defined frequency for a wide range of wave numbers. It has been observed that heavy particles have a more relevant role on the mass current correlations whereas light particles play a dominant role on the concentration current correlations. The overall results for the three kinds of liquid mixtures analysed in this paper show that both the longitudinal and transverse current spectra are little dependent on the static structure of the system whereas marked differences are revealed when the particles in the system are either neutral or carry an electric charge.     

Molecular Dynamics Simulation of Model Lipid Membranes: Structural Effects of Impurities

Abstract

The gel to fluid phase transition or ordered to disordered phase transition observed in biological membranes are simulated by using constant energy Molecular Dynamics. The surface part of the membrane is modelled as a two-dimensional matrix formed by the head groups of the phospholipid molecules. Head molecules which are modelled as three spheres fused with three force centers, interact with each other via van der Waals and Coulomb type interactions. The -so called- impurity or foreign molecule embedded in the surface represents the protein type molecule which is present in biological membranes and control its activity. It is modelled as a pentagon having one force centers in each corner. It also interacts with the surface molecules again via van der Waals and Coulomb type interactions. The surface density is kept constant in the simulations of the systems with or without impurity. Structural and orientational changes due to impurity were observed and proved by monitoring two-dimensional order parameter. It has been shown that melting of the surface or breakage of the ordering of the surface molecules becomes easier and ordered to disordered phase transition temperature was lowered by 100 K if the impurity is present.     

An Adiabatic Molecular Dynamics Method for the Calculation of Free Energy Profiles

A new molecular dynamics method for calculating free energy profiles for rare events is presented. The new method is based on the creation of an adiabatic separation between the reaction coordinate subspace and the remaining degrees of freedom within a molecular dynamics run. This is achieved by associating with the reaction coordinate(s) a high temperature and large mass, thereby allowing the activated process to occur while permitting the remaining degrees of freedom to respond adiabatically. In this limit, by applying a formal multiple time scale Liouville operator factorization, it can be rigorously shown that the free energy profiles are obtained directly from the probability distribution of the reaction coordinate subspace and, therefore, require no postprocessing of the output data. The new method is applied to a variety of model problems and its performance tested against free energy calculations using the "bluemoon ensemble" approach. The comparison shows that free energy profiles can be calculated with greater ease and efficiency using the new method.     

Multiple Time Step Brownian Dynamics for Long Time Simulation of Biomolecules

We report a multiple time step algorithm applied to an atomistic Brownian dynamics simulation for simulating the long time scale dynamics of biomolecules. The algorithm was based on the original multiple time step method; a short time step was used to keep faster motions in local equilibrium. When applied to a 28-mer # # ! folded peptide, the simulation gave stable trajectories and the computation time was reduced by a factor of 160 compared to a conventional molecular dynamics simulation using explicit water molecules. We applied it for the folding simulation of a 13-mer ! -helical peptide, giving a successful folding simulation. These results indicate that the Brownian dynamics with the multiple time step algorithm is useful for studies of biomolecular motions by long time simulation.     

Calculating Free Energies Using a Scaled-Force Molecular Dynamics Algorithm

We propose and test a family of methods to calculate the free energy along a generalized coordinate, , based on computing the force acting on this coordinate. First, we derive a formula that connects the free energy in unconstrained simulations with the force of constraint that can be readily calculated numerically. Then, we consider two methods, which improve the efficiency of the free energy calculation by yielding uniform or nearly uniform sampling of . Both rely on modifying the force acting on . In one method, this force is replaced by a force with zero mean and is advanced quasistatically. In the second method, the force is augmented adaptively by a biasing force. We provide formulas for calculating the free energy of the unmodified system from the forces acting in these modified, non-Hamiltonian systems. Using conformational transitions in 1,2-dichloroethane as a test case, we show that both methods perform very well.     

Modeling Confined Fluids: An NhPT Molecular Dynamics Method

We present an NhPT MD method developed for systematic investigation of both the structural and dynamical properties of confined fluids without resorting to chemical potential or explicit reservoir. This method allows confined fluids to expand or contract transversely and the same number of fluid molecules to be simulated throughout all surface separations. Its first implementation using confined Lennard-Jones fluid yields step-like changes in surface density, layered configurations, in-plane ordering, and oscillatory perpendicular pressures and transverse diffusivities that are consistent with previous studies. Additionally, a pseudo-Poisson's ratio and transverse isothermal compressibility were calculated. Like other properties, they oscillate at smaller surface separations and approach constant values when the surface separation becomes sufficiently large. The limiting value of the pseudo-Poisson's ratio is interestingly equivalent to that of incompressible continua.     

嗜温冷休克蛋白力致去折叠研究

嗜温冷休克蛋白拥有一个由五个β股形成的反平行β桶结构,目前已被用于蛋白质去折叠的研究。当使用机械力对嗜温冷休克蛋白进行拉伸研究时,发现嗜温冷休克蛋白的去折叠过程具有明显的中间态。在常速和常力两种情况下对嗜温冷休克蛋白进行拉伸分子动力学模拟,发现其在两种情况下具有相同的去折叠次序,即C端β片层首先去折叠,随后N端β片层去折叠;同时这两种模拟都表现出明确的中间态。研究结果表明,嗜温冷休克蛋白抵抗外力作用除了依赖链间氢键外,分子内的静电相互作用也发挥着重要的作用。     

A Molecular Dynamics Simulation Study of Rigid and Non-rigid Hard Dumb-bells

Abstract

We present a comparative study, using molecular dynamics, of systems of diatomic, hard dumb-bell, molecules in which the interatomic distance is either constrained to a fixed value or is allowed to vary freely between preset limits. A significant improvement in simulation effciency can be attained by allowing the bond length to vary. We find that thermodynamic properties, and some time correlation functions, are only slightly affected by the removal of the rigid bond-length constraint. The atomic velocity correlation function responds dramatically at short times to changes in the degree of non-rigidity, but at long times these differences are much less important.     

Structural and Dynamical Studies of Humanin in Water and TFE/Water Mixture: A Molecular Dynamics Simulation

Summary

Proline-rich peptides are known to adopt preferentially the extended polyproline II (PPII) helical conformation, which is involved in several protein-protein recognition events. By resorting to molecular modelling techniques, we wished to investigate the extent to which PPII helices could be used for the formation of isohelical peptide-DNA complexes leading to the selective recognition of the major groove of B-DNA. For that purpose, we have grafted to a cationic intercalator, 9-amino-acridine, an oligopeptide having the sequence: Pro-Arg-Pro-Pro-Arg-Pro-Pro-Arg-Pro-Pro-Asp-Pro-Pro. Each residue in the sequence was set in the D configuration, to prevent enzymatic hydrolysis, and each Arg residue was designed to target O6/N7 of a guanine base following the intercalation site. The Asp residue was designed to target a cytosine base, whilst simultaneously forming a bidentate complex with the Arg three residues upstream. Energy-minimization, using the JUMNA procedure, led to the following conclusions: 1) major groove binding is favoured over minor groove or exclusive binding to the phosphates by large energy differences, of over 50 and 90 kcal/mole, respectively; 2) the two best bound sequences are those having three successive guanine bases on the same DNA strand, immediately adjacent to the intercalation site. Sequence d(CGGGC G), encountered in the Primer Binding Site of the HIV retrovirus, thus ranks amongst the best-bound sequences; 3) replacement of an individual guanine amongst the three ones upstream of the intercalation site, by an adenine base, weakens by > 6 kcal/mole the binding energetics; 4) the conformational rigidity of the DNA-bound PPII helix should enable for a modulation of the base sequence selectivity, by appropriate replacements of the Arg and Asp residues. Thus sequence CGGCAAG, also encountered in the HIV genome, could be targeted by an oligopeptide having the sequence Pro-Arg-Pro-Pro-Asp-Pro-Pro- Asn-Pro-Pro-Asn-Pro-Pro-Arg-Ala.     

Molecular Dynamics Simulation of Limiting Conductance for Li + Ion in Supercritical Water using Polarizable Models

We report results of molecular dynamics simulations of the limiting conductance of Li + ion in ambient water and in supercritical water using polarizable models for water and Li + . The limiting conductances of Li + in ambient water calculated from mean square displacement (MSD) using four points transferable intermolecular potential model (TIP4P), extended simple point charge model (SPC/E), and revised polarizable model 1 (RPOL1) are larger than the experimental value. The behavior of the limiting conductance of Li + in supercritical water using the RPOL models results in good agreement with experimental results for the limiting conductance of LiCl. The agreement of the RPOL1 model with the experimental results is much better than the RPOL2 model in the higher-density regime, whereas that of the RPOL2 model is much better than the RPOL1 model in the lower-density regime. Using the RPOL models (in contrast to the SPC/E model), the number of hydration water molecules around Li + is the dominating contributor to the limiting conductance in the higher-density regime. In agreement with the SPC/E model, the interaction strength between Li + and the hydration water molecules is a non-factor in the lower-density region since the potential energy per hydration water molecule decreases with decreasing water density at the lowest water densities.     

Conformational Studies of Two Bradykinin Antagonists by Using Two-dimensional NMR Techniques and Molecular Dynamics Simulations

Abstract

The solution conformations of two potent antagonists of bradykinin (Arg¹-Pro²-Pro³-Gly⁴- Phe⁵-Ser⁶-Pro⁷-Phe⁸-Arg⁹), [Aca-¹, DArg⁰, Hyp³, Thi⁵, DPhe⁷,(N-Bzl)Gly⁸]BK (1) and [Aaa- ¹, DArg⁰, Hyp³, Thi⁵,(2-DNal)⁷, Thi⁸]BK (2), were studied by using 2D NMR spectroscopy in DMSO-dg and molecular dynamics simulations. The NMR spectra of peptide 1 reveals the existence of at least two isomers arising from isomerization across the DPhe⁷-(N-Bzl)Gly⁸peptide bond. The more populated isomer possesses the cis peptide bond at this position. The ratio of cis/trans isomers amounted to 7:3. With both antagonists, the NMR data indicate a β-turn structure for the Hyp³-Gly⁴ residues. In addition, for peptide 2, position 2,3 is likely to be occupied by turn-like structures. The cis peptide bond between DPhe⁷ and (N- Bzl)Gly⁸ in analogue 1 suggests type VI β-turn at position 7,8. The molecular dynamics runs were performed on both peptides in DMSO solution. The results indicate that the structure of peptide 1 is characterized by type VIb β-turn comprising residues Ser-Arg⁹ and the βI or βII-turn involving the Pro²-Thi⁵ fragment, whereas peptide 2 shows the tendency towards the formation of type I β-turn at position 2,3. The structures of both antagonists are stabilized by a salt bridge between the guanidine moiety of Arg¹ and the carboxyl group of Arg⁹. Moreover, the side chain of DArg⁰ is apart of the rest of molecule and is not involved in structural elements except for a few calculated structures.