The methods of computer simulation in all-atom and coarse-grained approximations have been used to study specific interactions of the isolated domain I-BAR of the actin-binding protein IRSp53 with model membranes containing neutral phospholipids and those including negatively charged PI(4,5)P2 phospholipids. It has been shown that the I-BAR domain does not interact with neutral lipids but induces bending of the synthetic membrane rich in negatively charged phospholipids. Clustering of charged lipids on the surface of the membrane at the sites of its interaction with the protein has been observed. This indicates that the interaction of I-BAR with negatively charged lipids is of electrostatic and hydrophobic nature.

The three-dimensional structure of the 5-HT3 receptor is currently unknown. An available structure of the nicotinic acetylcholine receptor closely related by homology to the 5-HT3 receptor was used as a template for the computer-based homology modeling of the 5-HT3 receptor. The study of the ion migration through the channel by the steered molecular dynamics method has shown that the steric factor in the region of residue Thr279 and the region of Glu272, Asp293 influences the ion transmission. The characteristic of the close interaction between the ion and the amino acid substitutions of the 5-HT3 channel was studied by computing the energy profile using constraint force molecular dynamic simulations. The amino acid sequence responsible for selective ion transmission has been investigated. The structure of the channel domain of the serotonin 5-HT3 receptor as a universal functional unit of the ligand-gated ion channels was discussed.

The authors show that method of molecular dynamics [1, 2, 3] can be used to study interaction between molecule of zervamicin IIB and of eukaryotic and prokaryotic cells. Lipid bilayer consisting of palmitoiloleoilphosphatidilholin (POPhH) was used to model membrane of eukaryotic cell. Lipid bilayer of palmitoiloleoilphosphatidilglycerol (POPhG) and palmitoiloleoilphosphatidilethanolamin (POPhE) in proportion 1:4 was used to model bacterial cell. Zervamicin molecules ability to aggregate on a membranes surface was researched. In addition two-way influence of peptides on a binding and incorporation process.

The structural properties and dynamic behavior of the antimicrobial peptide melittin in hydrophobic and polar environments have been investigated. The main characteristics of the secondary structure of melittin in different media have been analyzed and compared with the data on an ideal α-helix. It has been shown that melittin is an α-helix bent in the region of Pro14; the N-terminus of the peptide tends to unfold, while the C-terminal segment (residues 14–23) retains a helical structure for 20 ns of the simulation. 2,2,2-Trifluoroethanol molecules stabilize the helical structure of the peptide by lowering the dielectric constant of the environment and preferentially accumulating near particular sites of the polypeptide chain.

The structural properties and dynamic behavior of the antimicrobial peptide melittin in hydrophobic and polar environments have been investigated. The main characteristics of the secondary structure of melittin in different media have been analyzed, and compared with the data on the ideal alpha-helix. It has been shown that melittin is an alpha-helix bent in the region of residue Pro14; in this case, the N-terminus of the peptide tends to unfold, while the C-terminal segment (residues 14-23) retains the helical structure for 20 ns of the simulation. 2,2,2-Trifluoroethanol molecules stabilize the helical structure of the peptide through lowering the dielectric constant of the environment and preferential accumulation nearby particular segments of the polypeptide chain.

Cobra cytotoxins, small proteins of three-fingered toxin family, unspecifically damage membranes in different cells and artificial vesicles. However, the molecular mechanism of this damage is not yet completely understood. We used steered molecular dynamics simulations to study the interaction of cardiotoxin A3 from Naja atra cobra venom with hydrated 1-palmitoyl-2-oleoyl-1-sn-3-phosphatidylcholine (POPC) bilayer. The studied system included one cytotoxin molecule, 64 lipid molecules (32 molecules in each monolayer) and 2500 water molecules. It was found that the toxin interacted with zwitterionic bilayer formed by POPC. During first nanosecond of simulation the toxin molecule was oriented toward membrane surface by loops' basement including cytotoxin regions Cys14-Asn19 and Cys38-Ser46. This orientation was stable enough and was not changed during next 6 ns of simulation. The obtained data suggest that cytotoxin molecule cannot penetrate into membrane composed of zwitterionic lipids without some auxiliary interaction.

The molecular dynamics of dipeptides of natural amino acids were examined using protocols that do not violate the principle of equal distribution of energy over the degrees of freedom. Comparative analysis involved autocorrelation functions of complex exponentials from dihedrals. The mutual influence of residues was classified by the effects on the dynamic properties of the neighbors.

A comparative study has been made of the molecular dynamics of zervamicin II (an antimicrobial peptide of the peptaibol group, which has channel-forming activity) in water and methanol. The influence of amino acid substitutions on the dynamics and stability of the peptide structure has been investigated. The amino acid sequence responsible for the absence of swivel motions in short peptaibols has been determined.

A comparative study of several model lipid bilayers of different composition, which included analysis of kinetic parameters of model lipid bilayers and permeability of bilayer membranes for small molecules, has been carried out. The conformity of results of numeric experiments to experimental data (structure of membrane lipid bilayers, lateral diffusion coefficients, and relative permeability of biomembranes for ligands) is discussed in the framework of a standard molecular dynamics protocol.

Методом молекулярной динамики проведено сравнительное изучение липидных бислоев различного состава. Использован метод управляемой молекулярной динамики для оценки кинетических параметров и проникновения малых молекул разной химической природы через биомембраны. В рамках единого протокола молекулярного моделирования обсуждается соответствие результатов численного эксперимента с данными по структуре биомембран, коэффициентам латеральной диффузии и сравнительной проницаемости мембран для различных лигандов.

We use molecular dynamics simulation to examine the conformational possibilities in solution for the peptide MEHFPGP (Semax) representing the minimal nootropic fragment of MSH, and its versions with N-terminal substitutions of K, G, or R for M. We discuss the possible relationship between molecule structure and physiological activity, considering the influence of Coulomb interactions on the dynamics and the putative stabilization of a certain peptide conformation at pH < 6.

Weak toxins are the "three-fingered" snake venoms toxins grouped together by having an additional disulfide in the N-terminal loop I. In general, weak toxins have low toxicity, and biological targets have been identified for some of them only, recently by detecting the effects on the nicotinic acetylcholine receptors (nAChR). Here the methods of docking and molecular dynamics simulations are used for comparative modeling of the complexes between four weak toxins of known spatial structure (WTX, candoxin, bucandin, gamma-bungarotoxin) and nAChRs. WTX and candoxin are those toxins whose blocking of the neuronal alpha7- and muscle-type nAChR has been earlier shown in binding assays and electrophysiological experiments, while for the other two toxins no such activity has been reported. Only candoxin and WTX are found here to give stable solutions for the toxin-nAChR complexes. These toxins appear to approach the binding site similarly to short alpha-neurotoxins, but their final position resembles that of alpha-cobratoxin, a long alpha-neurotoxin, in the complex with the acetylcholine-binding protein. The final spatial structures of candoxin and WTX complexes with the alpha7 neuronal or muscle-type nAChR are very similar and do not provide immediate answer why candoxin has a much higher affinity than WTX, but both of them share a virtually irreversible mode of binding to one or both these nAChR subtypes. Possible explanation comes from docking and MD simulations which predict fast kinetics of candoxin association with nAChR, no gross changes in the toxin conformation (with smaller toxin flexibility on alpha7 nAChR), while slow WTX binding to nAChR is associated with slow irreversible rearrangement both of the tip of the toxin loop II and of the binding pocket residues locking finally the toxin molecule. Computer modeling showed that the additional disulfide in the loop I is not directly involved in receptor binding of WTX and candoxin, but it stabilizes the structure of loop I which plays an important role in toxin delivery to the binding site. In summary, computer modeling visualized possible modes of binding for those weak toxins which interact with the nAChR, provided no solutions for those weak toxins whose targets are not the nAChRs, and demonstrated that the additional disulfide in loop I cannot be a sound criteria for joining all weak toxins into one group; the conclusion about the diversity of weak toxins made from computer modeling is in accord with the earlier phylogenetic analysis.

A comparative study of the molecular dynamics of natural amino acid residues and their closest homologues and isomers was carried out. Molecular dynamics protocols not interfering with the principle of equidistribution of energy with respect to degrees of freedom were used. Poincare cross-sections, auto- and cross-correlation of complex exponential curves as a function of dihedrons were considered. The classification of dynamic properties of conformational degrees of freedom in the series of amino acid residues was carried out.