Aqueous peptides as experimental models for hydration water dynamics near protein surfaces

We report quasi-elastic neutron scattering experiments to contrast the water dynamics as a function of temperature for hydrophilic and amphiphilic peptides under the same level of confinement, as models for understanding hydration dynamics near chemically heterogeneous protein surfaces. We find that the hydrophilic peptide shows only a single non-Arrhenius translational process with no evidence of spatial heterogeneity unlike the amphiphilic peptide solution that exhibits two translational relaxations with an Arrhenius and non-Arrhenius dependence on temperature. Together these results provide experimental proof that heterogeneous dynamical signatures near protein surfaces arise in part from chemical heterogeneity (energy disorder) as opposed to mere topological roughness of the protein surface.     

Molecular dynamics simulation of water near nanostructured hydrophobic surfaces: interfacial energies.

We present results from molecular dynamics simulations of water near structured hydrophobic surfaces. The surface structures reported herein are a planar alkane crystal as a reference and crystals with a hole and a protrusion of approximately 2.5 nm diameter and 0.5 nm depth or height. All indicators show that surface structuring increases the hydrophobicity: The water density is reduced near the structure elements, and the number of residual contacts between water and the surface decreases by about 40 % with respect to the planar surface. Thermodynamic integration shows that the interfacial energy of the structured surfaces is about 7 mJ m(-2) higher for structured surfaces than for the planar surface. The hydrophobicity increases by a similar amount for the hole and the protrusion geometries compared to the planar surface.     

液态水的分子动力学模拟

用分子动力学(MD)模拟方法在150~376K的温度范围内对液态水的微正则系统进行了研究。考察了液态水的结构及其性质。模拟采用了由从头算得出的柔性水-水相互作用势MCYL。对时间和空间的平均得出了液态中水分子几何构型及温度改变所引起的液态水结构变化。对径向分布函数gOH, gOO, gHH及配位数的分析表明, 在所考察的温度范围内, 每个水分子与相邻分子形成的氢键数为2~3, 水分子在参与的2个氢键中同时作为授受体。结合对振动谱的研究表明在低温时液态水形成的网络结构可能随温度的升高而形成小的簇结构。     

A molecular dynamics study of water near silicate surfaces

We have conducted a molecular dynamics simulation of water between uncharged silicate surfaces in order to understand, on a molecular basis, the structural and dynamical properties of vicinal water (i.e., the water between the surfaces). The results of our preliminary simulation indicate that the vicinal water differs substantially from pure bulk water in the transient orientation of molecular dipole moments and rate of relaxation of these moments. In contrast, no significant long-range differences between the radial distribution functions or hydrogen bonding patterns of vicinal and bulk water are evident.     

Molecular dynamics simulation of cellobiose in water

The conformational behavior of cellobiose was studied by molecular dynamics simulation in a periodic box of waters. Several different initial conformations were used and the results compared with equivalent vacuum simulations. The average positions and rms fluctuations within single torsional conformations of cellobiose were affected only slightly by the solvent. However, water damped local torsional librations and transitions. The conformational energies of the solute and their fluctuations were also sensitive to the presence of solvent. Intramolecular hydrogen bonding was weakened relative to that observed in vacuo due to competition with solvating waters. All cellobiose hydroxyl groups participated in intermolecular hydrogen bonds with water, with approximately eight hydrogen bonds formed per glucose ring. The hydrogen bonding was predominantly between water hydrogens and solute hydroxyl oxygens. Intermolecular hydrogen bonding to ring and bridge oxygens was seldom present. The diffusion coefficients of both water and solute agree closely with experimental values. Water interchanged rapidly between the solvating first shell and the bulk on the picosecond time scale. © 1993 John Wiley & Sons, Inc.     

Molecular dynamics study of crystalline water ices

The behavior of structures of H₂O crystalline ices Ih, Ic, XI, VII, VIII, VI is studied in molecular dynamics experiment using the potential offered by Poltev and Malenkov. The behavior of the system consisting of one of the two identical interpenetrating, but without any common hydrogen bonds, water frameworks comprising the ice VI structure is also simulated. As a result of simulations, the ice VII structure has collapsed, whereas other systems proved to be stable. The reasons of instability of the ice VII and previously studied ice IV structures in molecular dynamics experiments are discussed. Based on the simulation results of the above-mentioned ices and previous simulation of ices II, III, IX, IV, and XII, the general regularities of dynamic properties of water molecules in crystalline water ices are formulated. Unreliability of results obtained by molecular dynamics in the investigation of self-organizing processes in aqueous systems is shown.     

Molecular view of the role of fusion peptides in promoting positive membrane curvature

Fusion peptides are moderately hydrophobic segments of viral and nonviral membrane fusion proteins that enable these proteins to fuse two closely apposed biological membranes. In vitro assays furthermore show that even isolated fusion peptides alone can support membrane fusion in model systems. In addition, the fusion peptides have a distinct effect on the phase diagram of lipid mixtures. Here, we present molecular dynamics simulations investigating the effect of a particular fusion peptide, the influenza hemagglutinin fusion peptide and some of its mutants, on the lipid phase diagram. We detect a systematic shift toward phases with more positive mean curvature in the presence of the peptides, as well as an occurrence of bicontinuous cubic phases, which indicates a stabilization of Gaussian curvature. The wild-type fusion peptide has a stronger effect on the phase behavior as compared to the mutants, which we relate to its boomerang shape. Our results point to a different role of fusion peptides than hitherto assumed, the stabilization of pores rather than stalks along the fusion pathway.     

Molecular dynamics simulation study on the structural stabilities of polyglutamine peptides

It is known that Huntington's disease patients commonly have glutamine (Q) repeat sequences longer than a critical length in the coding area of Huntingtin protein in their genes. As the polyglutamine (polyQ) region becomes longer than the critical length, the disease occurs and Huntingtin protein aggregates, both in vitro and in vivo, as suggested by experimental and clinical data. The determination of polyglutamine structure is thus very important for elucidation of the aggregation and disease mechanisms. Here, we perform molecular dynamics calculations on the stability of the structure based on the β-helix structure suggested by Perutz et al. (2002) [Perutz, M.F., Finch, J.T., Berriman, J., Lesk, A., 2002. Amyloid fibers are water-filled nanotubes. Proc. Natl. Acad. Sci. USA 99, 5591]. We ensure that perfect hydrogen bonds are present between main chains of the β-helix based on the previous studies, and perform simulations of stretches with 20, 25, 30, 37 and 40 glutamine residues (20Q, 25Q, 30Q, 37Q and 40Q) for the Perutz models with 18.5 and 20 residues per turn (one coil). Our results indicate that the structure becomes more stable with the increase of repeated number of Q, and there is a critical Q number of around 30, above which the structure of the Perutz model is kept stable. In contrast to previous studies, we started molecular dynamics simulations from conformations in which the hydrogen bonds are firmly formed between stacked main chains. This has rendered the initial β-helix structures of polyQ much more stable for longer time, as compared to those proposed previously. Model calculations for the initial structures of polyQ dimer and tetramer have also been carried out to study a possible mechanism for aggregation.     

Molecular dynamics simulations of beta-cyclodextrin-aziadamantane complexes in water

Force-field-based atomistic simulations of host-guest supramolecular complexes between beta-cyclodextrin and several aziadamantane derivatives have been analyzed with respect to relative orientation and interaction energies, explicitly considering solvent (water) molecules. For each case, the calculations revealed two stable orientations of the guest within the host that are different in interaction energy. Fluctuation of and correlation between characteristic properties were analyzed. Among other things, it turned out that orientation angle and inclusion depth are clearly correlated. In addition, for the unsubstituted aziadamantane, the enthalpy of complex formation was calculated and compared to experimental results.     

Molecular dynamics study on helium nanobubbles in water

Interfacial properties of helium nanobubbles in water at normal conditions have been investigated using large-scale molecular dynamics simulations for systems including over one million atoms. The surface tension of a helium nanobubble is a convex function with respect to the bubble radius, and is estimated to vanish at a critical radius of approximately 1 nm.     

Elastic bag model for molecular dynamics simulations of solvated systems: application to liquid water and solvated peptides

The fluctuating elastic boundary (FEB) model for molecular dynamics has recently been developed and validated through simulations of liquid argon. In the FEB model, a flexible boundary which consists of particles connected by springs is used to confine the solvated system, thereby eliminating the need for periodic boundary conditions. In this study, we extend this model to the simulation of bulk water and solvated alanine dipeptide. Both the confining potential and boundary particle interaction functions are modified to preserve the structural integrity of the boundary and prevent the leakage of the solute-solvent system through the boundary. A broad spectrum of structural and dynamic properties of liquid water are computed and compared with those obtained from conventional periodic boundary condition simulations. The applicability of the model to biomolecular simulations is investigated through the analysis of conformational population distribution of solvated alanine dipeptide. In most cases we find remarkable agreement between the two simulation approaches.     

Molecular dynamics study of the water/n-alkane interface

Molecular dynamics simulations on the interface between liquid water and liquid n-alkane (including octane, nonane, decane, undecane and dodecane) have been performed with the purpose to study the interfacial properties: (Ⅰ) density profile; (Ⅱ) molecular orientation; (Ⅲ) interfacial tension and the temperature effect on the interfacial tension. Simulation results show that at the interface the structures of both water and n-alkane are different from those in the bulk. Water has an orientational preference ...     

Molecular dynamics simulations of water droplets on polymer surfaces

Molecular dynamics simulations were used to study the wetting of polymer surfaces with water. Contact angles of water droplets on crystalline and two amorphous polyethylene (PE) and poly(vinyl chloride) (PVC) surfaces were extracted from atomistic simulations. Crystalline surfaces were produced by duplicating the unit cell of an experimental crystal structure, and amorphous surfaces by pressing the bulk polymer step by step at elevated temperature between two repulsive grid surfaces to a target density. Different-sized water droplets on the crystalline PE surface revealed a slightly positive line tension on the order of 10(-12)-10(-11) N, whereas droplets on crystalline PVC did not yield a definite line tension. Microscopic contact angles produced by the simple point charge (SPC) water model were mostly a few degrees smaller than those produced by the extended SPC model, which, as the model with lowest bulk energy, presents an upper boundary for contact angles. The macroscopic contact angle for the SPC model was 94 degrees on crystalline PVC and 113 degrees on crystalline PE. Amorphicity of the surface increased the water contact angle on PE but decreased it on PVC, for both water models. If the simulated contact angles on crystalline and amorphous surfaces are combined in proportion to the crystallinity of the polymer in question, simulated values in relatively good agreement with measured values are obtained.     

Molecular dynamics simulation of liquid water between two walls

A molecular dynamics simulation, lasting ≈25 ps, has been performed with 150 ST2 water molecules between two quasi-hard repulsive walls, at a temperature of 302 K. A number of static and dynamic properties have been computed as a function of the distance from the walls, showing that water near the walls is in general more “ordered” than in the bulk, and that this bulk water behaves like ordinarv liquid ST2 water.     

Molecular dynamics simulation of the water|nitrobenzene interface

The structure and dynamics of the neat water|nitrobenzene liquid|liquid interface are studied at 300 K using molecular dynamics computer simulations. The water is modeled using the flexible SPC potential, and the nitrobenzene is modeled using an empirically determined nitrobenzene potential energy function. Although nitrobenzene is a polar liquid with a large dielectric constant, the structure of the interface is similar to other water|non-polar organic liquid interfaces. Among the main structural features we describe are an enhancement of interfacial water hydrogen bonds, the specific orientation of water dipoles and nitrobenzene molecules, and a rough surface that is locally sharp. Surface roughness is also characterized dynamically. The dynamics of molecular reorientation are shown to be only mildly modified at the interface. The effect due to the polarizable many-body potential energy functions of both liquids is investigated and is found to affect only mildly the above results.     

Molecular dynamics simulation of a water/metal interface

First results of a molecular dynamics study of a water/metal interface, lasting 3.3 ps at an average temperature of 294 K, are reported. The basic periodic box contains 216 water molecules and a crystal slab of 550 platinum atoms with (100) surface planes. A combination of a Lennard-Jones potential between centers of mass and a Coulomb potential arising from dielectric interactions of the water charge distribution with the metal is employed for the water-wall interaction, the ST2 model for the water-water, and a nearest-neighbour harmonic potential for the platinum-platinum interactions. Considerable adsorption at the interface together with a drastic change of the water structure is observed.     

Molecular dynamics study of peptides in implicit water: ab initio folding of beta-hairpin, beta-sheet, and beta beta alpha-motif

In this communication, we have demonstrated that molecular dynamics simulations using a GB implicit solvation model with the all-atom based force field (CHARMM19) can describe the spontaneous folding of small peptides in aqueous solution. The native structures of peptides with various structural motifs (beta-hairpin, beta-sheet, and betabetaalpha-moiety) were successfully predicted within reasonable time scales by MD simulations at moderately elevated temperatures. It is expected that the present simulations provide further insight into mechanism/pathways of the peptide folding.     

Molecular dynamics simulation of aqueous NaF and NaI solutions near a hydrophobic surface

We present results from molecular dynamics simulation of aqueous solutions of alkali halide salts (NaI and NaF) at the interface with hydrophobic objects. The primary objective of this study is to investigate the structural properties of the salt solutions at the hydrophobic surface. An alkane crystal has been taken as the parent model for a hydrophobic surface. A hexagonal hole was created on it, which was half a nm deep and 2.5 nm wide. The density distributions of different species (water, anions, and cations) are studied as a function of distance from the surface. While iodide prefers the interface, the fluoride ions stay inside the bulk water region. The higher concentration of iodide ions at the interface drags sodium counterions to the interface. It also decreases the water density at the interface because of steric effects of the iodide ions. The number of contacts between the surface carbons and water decreases in the case of NaI solutions but is unchanged for NaF solutions. The orientation of the water-ion and the water-water hydrogen bond vector orientations near the interface is discussed in detail.     

Molecular dynamics simulations of proteins and peptides: from folding to drug design

Computer simulations of proteins, lipids and nucleic acids at equilibrium have become essentially routine. However, the fact remains that complete sampling of conformational space continues to be a bottle-neck in the field. The challenge for the future is to overcome such problems and use computational approaches to understand recognition and spontaneous self-organization in biomolecular systems (folding, aggregation and assembly of complexes), processes that cannot be directly observed experimentally. In this review, examples illustrating the extent to which simulations can be used to understand these phenomena in biomolecular systems will be presented along with examples of methodological developments to increase our physical understanding of the processes. The study cases will cover the problems of peptide-receptor recognition and the use of the information obtained for the design of new non-peptidic ligands; the study of the folding mechanism of small proteins and finally the study of the initial stages of peptide self-aggregation.