K V Shaitan

Publications (30)17.79 Total impact

• Article: The effects of confluency on cell mechanical properties.

  Yu M Efremov, A A Dokrunova, D V Bagrov, K S Kudryashova, O S Sokolova, K V Shaitan
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  ABSTRACT: Mechanical properties of cells depend on various external and internal factors, like substrate stiffness and surface modifications, cell ageing and disease state. Some other currently unknown factors may exist. In this study we used force spectroscopy by AFM, confocal microscopy and flow cytometry to investigate the difference between single non-confluent and confluent (in monolayer) Vero cells. In all cases the stiffness values were fitted by log-normal rather than normal distribution. Log-normal distribution was also found for an amount of cortical actin in cells by flow cytometry. Cells in the monolayer were characterized by a significantly lower (1.4-1.7 times) Young's modulus and amount of cortical actin than in either of the single non-confluent cells or cells migrating in the experimental wound. Young's modulus as a function of indentation speed followed a weak power law for all the studied cell states, while the value of the exponent was higher for cells growing in monolayer. These results show that intercellular contacts and cell motile state significantly influence the cell mechanical properties.
  Journal of biomechanics 02/2013; · 2.66 Impact Factor
• Source

  Available from: Nurbubu Tentievna Moldogazieva

  Article: Correlation between biological activity and conformational dynamics properties of tetra- and pentapeptides derived from fetoplacental proteins.

  N T Moldogazieva, A A Terentiev, M Yu Antonov, A N Kazimirsky, K V Shaitan
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  ABSTRACT: In this work, using molecular dynamics simulation, we study conformational and dynamic properties of biologically active penta- and tetrapeptides derived from fetoplacental proteins such as alpha-fetoprotein, pregnancy specific β1-glycoprotein, and carcinoembryonic antigen. Existence of correlation between flexibility of peptide backbone and biological activity of the investigated peptides was shown. It was also demonstrated that flexibility of peptide backbone depends not only on its length, but also on the presence of reactive functional groups in amino acid side chains that participate in intramolecular interactions. Peptides that demonstrate similar biological effects in regulation of proliferation of lymphocytes and expression of differentiation antigens on their surface (LDSYQCT, PYECE, YECE, and YVCE) are characterized by rigidity of their peptide backbone. Increased backbone flexibility in peptides PYQCE, YQCE, SYKCE, YQCT, YQCS, YVCS, YACS, and YACE is correlated with decreased biological activity. Conformational mobility of amino acid residues does not depend on physicochemical properties only, but also on intramolecular interactions. So, evolutionary restrictions should exist to maintain such interactions in the environment of functionally important sites.
  Biochemistry (Moscow) 05/2012; 77(5):469-84. · 1.06 Impact Factor
• Article: A molecular dynamics study of the interaction between domain I-BAR of the IRSp53 protein and negatively charged membranes

  O. V. Levtsova, I. D. Davletov, O. S. Sokolova, K. V. Shaitan
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  ABSTRACT: 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. Keywordsmolecular dynamics–conformational changes–protein-lipid interactions
  Biophysics 04/2012; 56(2):220-224.
• Article: Molecular dynamics of human alpha-fetoprotein fragment LDSYQCT and its analogs at different dielectric constants

  N. T. Moldogazieva, K. V. Shaitan, K. B. Tereshkina, Yu. M. Antonov, A. A. Terentiev
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  ABSTRACT: A comparative study of the conformation dynamics of the human alpha-fetoprotein fragment LDSYQCT and heptapeptides derived from it by point substitutions has revealed a significant influence of electrostatic interactions on the set of preferred conformations and dynamics of amino acid residues when the peptides with blocked termini are examined at ɛ = 1. Peptide flexibility rises when the termini are left free (charged). At ɛ = 10 or 80, the set of probable conformations for all residues expands to much the same extent, i.e., at higher permittivity of the medium the dynamic effects of amino acid changes are leveled off.
  Biophysics 04/2012; 52(4):365-374.
• Source

  Available from: Anton Bonartsev

  Article: Poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate)-based biopolymer systems

  A. P. Bonartsev, G. A. Bonartseva, K. V. Shaitan, M. P. Kirpichnikov
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  ABSTRACT: Biodegradable biopolymers attract much attention in biology and medicine due to its wide application. The present review considers a biodegradable and biocompatible polymer of bacterial origin, poly(3-hydroxybutyrate), which has wide perspectives in medicine and pharmaceutics. It highlights basic properties of biopolymer (biodegradability and biocompatibility) and also biopolymer systems: various materials, devices and compositions based on the biopolymer. Application of poly(3-hydroxybutyrate)-based biopolymer systems in medicine as surgical implants, in bioengineering as cell culture scaffolds, and in pharmacy as novel drug dosage forms and drug systems are also considered. Keywordsbiopolymer system–polyhydroxyalkanoates (PHA)–poly(3-hydroxybutyrate) (PHB)–biodegradation–biocompatibility
  Biochemistry (Moscow) Supplement Series B Biomedical Chemistry 04/2012; 5(1):10-21.
• Article: Atomic force microscopy of animal cells: Advances and prospects

  Yu. M. Efremov, D. V. Bagrov, E. V. Dubrovin, K. V. Shaitan, I. V. Yaminskii
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  ABSTRACT: We review the advances of the method of atomic force microscopy (AFM) for investigating the animal cells and analyze its development, paying much attention to studies of living cells. We consider the specific features and tasks of AFM, and a number of special AFM-based techniques. We discuss the choice of probe geometry for studies of animal cells, determination of cell adhesion on substrate, mapping of the cell surface using chemically modified cantilevers, and analysis of the distribution of molecular components inside the cell with the use of micro- and nanosurgical approaches, as well as combining AFM with optical and laser scanning confocal microscopy, and the possible applications of AFM in biotechnology and medicine. Keywordsatomic force microscopy–force spectroscopy–microsurgery–living cells–animal cells–cell adhesion–cantilever modification
  Biophysics 04/2012; 56(2):257-267.
• Article: Comparative study of molecular dynamics, diffusion, and permeability for ligands in biomembranes of different lipid composition

  K. V. Shaitan, M. Yu. Antonov, Ye. V. Tourleigh, O. V. Levtsova, K. B. Tereshkina, I. N. Nikolaev, M. P. Kirpichnikov
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  ABSTRACT: 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.
  Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology 04/2012; 2(1):73-81.
• Article: Comparative molecular dynamics study of the structural properties of melittin in water and trifluoroethanol/water

  T. V. Naumenkova, O. V. Levtsova, I. N. Nikolaev, K. V. Shaitan
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  ABSTRACT: 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. Key wordsantimicrobial peptide-melittin-molecular dynamics-secondary structure-2,2,2-trifluoroethanol
  Biophysics 04/2012; 55(1):24-28.
• Source

  Available from: Yuri Efremov

  Article: Atomic force microscopy as a tool to study Xenopus laevis embryo

  E A Pukhlyakova, Yu M Efremov, D V Bagrov, N N Luchinskaya, D O Kiryukhin, L V Belousov, K V Shaitan
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  ABSTRACT: Atomic force microscopy (AFM) has become a powerful tool for imaging biological structures (from single molecules to living cells) and carrying out measurements of their mechanical properties. AFM provides three-dimensional high-resolution images of the studied biological objects in physiological environment. However there are only few AFM investigations of fresh tissue explants and virtually no such research on a whole organism, since most researchers work with cell cultures. In the current work AFM was used to observe the surface of living and fixed embryos and to measure mechanical properties of naive embryos and embryos with overexpression of guanine nucleotide-binding protein G-alpha-13.
  Journal of Physics Conference Series 01/2012;
• Source

  Available from: Nurbubu Tentievna Moldogazieva

  Article: Influence of intramolecular interactions on conformational and dynamic properties of analogs of heptapeptide AFP(14-20).

  N T Moldogazieva, K V Shaitan, M Yu Antonov, I K Vinogradova, A A Terentiev
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  ABSTRACT: Conformational and dynamic properties of proteins and peptides play an important role in their functioning. However, mechanisms that underlie this influence have not been fully elucidated. In the present work we computationally constructed analogs of heptapeptide AFP(14-20) (LDSYQCT) - one of the biologically active sites of human α-fetoprotein (AFP) - to study their conformational and dynamic properties using molecular dynamics simulation. Analogs were obtained by point substitutions of amino acid residues taking into account differences in their physicochemical properties and also on the basis of analysis of amino acid substitutions in the AFP(14-20)-like motifs revealed in different physiologically active proteins. It is shown that changes in conformational mobility of amino acid residues of analogs are due to disruption or arising of intramolecular interactions that, in turn, determine existence of steric restrictions during rotation around covalent bonds of the peptide backbone. Substitution of an amino acid by another one with significant difference in physicochemical properties may not lead to remarkable changes in conformational and dynamic properties of the peptide if intramolecular interactions remain unchanged.
  Biochemistry (Moscow) 12/2011; 76(12):1321-36. · 1.06 Impact Factor
• Source

  Available from: Yuri Efremov

  Article: Atomic force microscopy study of the arrangement and mechanical properties of astrocytic cytoskeleton in growth medium.

  Yu M Efremov, E V Dzyubenko, D V Bagrov, G V Maksimov, S I Shram, K V Shaitan
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  ABSTRACT: Astrocytes are quite interesting to study because of their role in the development of various neurodegenerative disorders. The present work describes an examination of the arrangement and mechanical properties of cytoskeleton of living astrocytes using atomic force microscopy (AFM). The experiments were performed with an organotypic culture of dorsal root ganglia (DRG) obtained from a chicken embryo. The cells were cultivated on a gelatinous substrate and showed strong adhesion. AFM allows one to observe cytoskeleton fibers, which are interpreted as actin filaments and microtubules. This assumption is supported by confocal microscopy fluorescence imaging of α-tubulin and fibrillar actin. Mapping of the local Young's modulus of a living astrocyte showed that the stiff areas correspond to the sites where the cytoskeleton fibers are located. Thus, the data obtained indicate that AFM is a promising method to study neural cells cytoskeleton integrity and arrangement inin vitromodels of neurodegeneration.
  Acta naturae. 07/2011; 3(3):93-9.
• Article: Atomic force microscopy of living and fixed Xenopus laevis embryos.

  Yu M Efremov, E A Pukhlyakova, D V Bagrov, K V Shaitan
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  ABSTRACT: Xenopus laevis embryos are a rather simple and at the same time a very interesting animal model, which is widely used for research in developmental biology. Intensive coordinated cell movements take place during the multi-cellular organism development. Little is known of the cellular, molecular and biomechanical mechanisms of these movements. The conceptual framework for analysis of cell interactions within integrated populations is poorly developed. We have used atomic force microscopy (AFM) to observe the surface of fixed X. laevis embryos at different stages of their development. We have developed a new sample preparation protocol for these observations. The obtained images were compared with scanning electronic microscopy (SEM) data. Cell rearrangement during morphogenesis in vivo was also visualized by AFM. In the current paper we discuss facilities and challenges of using this technique for further embryo researching.
  Micron 06/2011; 42(8):840-52. · 1.53 Impact Factor
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  Available from: Nurbubu Tentievna Moldogazieva

  Article: Dynamic proteomics in modeling of the living cell. Protein-protein interactions.

  A A Terentiev, N T Moldogazieva, K V Shaitan
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  ABSTRACT: This review is devoted to describing, summarizing, and analyzing of dynamic proteomics data obtained over the last few years and concerning the role of protein-protein interactions in modeling of the living cell. Principles of modern high-throughput experimental methods for investigation of protein-protein interactions are described. Systems biology approaches based on integrative view on cellular processes are used to analyze organization of protein interaction networks. It is proposed that finding of some proteins in different protein complexes can be explained by their multi-modular and polyfunctional properties; the different protein modules can be located in the nodes of protein interaction networks. Mathematical and computational approaches to modeling of the living cell with emphasis on molecular dynamics simulation are provided. The role of the network analysis in fundamental medicine is also briefly reviewed.
  Biochemistry (Moscow) 12/2009; 74(13):1586-607. · 1.06 Impact Factor
• Article: Steered molecular dynamics simulations of cobra cytotoxin interaction with zwitterionic lipid bilayer: no penetration of loop tips into membranes.

  O V Levtsova, M Yu Antonov, D Yu Mordvintsev, Yu N Utkin, K V Shaitan, M P Kirpichnikov
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  ABSTRACT: 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.
  Computational biology and chemistry 08/2008; 33(1):29-32. · 1.37 Impact Factor
• Article: Conformational transitions in the nootropic peptide semax (MEHFPGP) and its N-terminal modifications

  K. V. Shaitan, K. B. Tereshkina, A. S. Kitaev, E. B. Tereshkin, O. V. Levtsova, M. Yu. Antonov, M. P. Akimov, I. N. Nikolaev
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  ABSTRACT: 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.
  Biophysics 03/2008; 53(2):121-124.
• Article: Conformational dynamics of human alpha-fetoprotein-derived heptapeptide LDSYQCT analogs.

  N T Moldogazieva, A A Terentiev, A N Kazimirsky, M Yu Antonov, K V Shaitan
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  ABSTRACT: Conformational dynamics of a biologically active fragment of alpha-fetoprotein, the heptapeptide LDSYQCT, and its analogs obtained by site-directed substitutions of amino acid residues were studied. The conformational dynamics of the peptide were conservative under the substitutions Y17F, Y17S, and D15E. Substitutions C19A and S16V resulted only in local changes in the dynamic behavior of the peptide. Chemical modification of cysteine (C19) or dimerization of the peptide by producing a disulfide bond between cysteine residues of two parallel peptide chains, as well as the substitutions C19G, C19S, Q18E, and D15N changed a set of possible conformations and dynamic behavior of all amino acid residues. The most significant changes were caused by substitution of uncharged amino acid residues by charged ones, and vice versa.
  Biochemistry (Moscow) 06/2007; 72(5):529-39. · 1.06 Impact Factor
• Source

  Available from: psu.edu

  Article: Computer modeling of binding of diverse weak toxins to nicotinic acetylcholine receptors.

  D Yu Mordvitsev, Ya L Polyak, D A Kuzmin, O V Levtsova, Ye V Tourleigh, Yu N Utkin, K V Shaitan, V I Tsetlin
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  ABSTRACT: 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.
  Computational Biology and Chemistry 04/2007; 31(2):72-81. · 1.55 Impact Factor
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  Available from: moldyn.org

  Article: A model for short alpha-neurotoxin bound to nicotinic acetylcholine receptor from Torpedo californica: comparison with long-chain alpha-neurotoxins and alpha-conotoxins.

  D Yu Mordvintsev, Ya L Polyak, O V Levtsova, Ye V Tourleigh, I E Kasheverov, K V Shaitan, Yu N Utkin, V I Tsetlin
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  ABSTRACT: Short-chain alpha-neurotoxins from snakes are highly selective antagonists of the muscle-type nicotinic acetylcholine receptors (nAChR). Although their spatial structures are known and abundant information on topology of binding to nAChR is obtained by labeling and mutagenesis studies, the accurate structure of the complex is not yet known. Here, we present a model for a short alpha-neurotoxin, neurotoxin II from Naja oxiana (NTII), bound to Torpedo californica nAChR. It was built by comparative modeling, docking and molecular dynamics using 1H NMR structure of NTII, cross-linking and mutagenesis data, cryoelectron microscopy structure of Torpedo marmorata nAChR [Unwin, N., 2005. Refined structure of the nicotinic acetylcholine receptor at 4A resolution. J. Mol. Biol. 346, 967-989] and X-ray structures of acetylcholine-binding protein (AChBP) with agonists [Celie, P.H., van Rossum-Fikkert, S.E., van Dijk, W.J., Brejc, K., Smit, A.B., Sixma, T.K., 2004. Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures. Neuron 41 (6), 907-914] and antagonists: alpha-cobratoxin, a long-chain alpha-neurotoxin [Bourne, Y., Talley, T.T., Hansen, S.B., Taylor, P., Marchot, P., 2005. Crystal structure of Cbtx-AChBP complex reveals essential interactions between snake alpha-neurotoxins and nicotinic receptors. EMBO J. 24 (8), 1512-1522] and alpha-conotoxin [Celie, P.H., Kasheverov, I.E., Mordvintsev, D.Y., Hogg, R.C., van Nierop, P., van Elk, R., van Rossum-Fikkert, S.E., Zhmak, M.N., Bertrand, D., Tsetlin, V., Sixma, T.K., Smit, A.B., 2005. Crystal structure of nicotinic acetylcholine receptor homolog AChBP in complex with an alpha-conotoxin PnIA variant. Nat. Struct. Mol. Biol. 12 (7), 582-588]. In complex with the receptor, NTII was located at about 30 A from the membrane surface, the tip of its loop II plunges into the ligand-binding pocket between the alpha/gamma or alpha/delta nAChR subunits, while the loops I and III contact nAChR by their tips only in a 'surface-touch' manner. The toxin structure undergoes some changes during the final complex formation (for 1.45 rmsd in 15-25 ps according to AMBER'99 molecular dynamics simulation), which correlates with NMR data. The data on the mobility and accessibility of spin- and fluorescence labels in free and bound NTII were used in MD simulations. The binding process is dependent on spontaneous outward movement of the C-loop earlier found in the AChBP complexes with alpha-cobratoxin and alpha-conotoxin. Among common features in binding of short- and long alpha-neurotoxins is the rearrangement of aromatic residues in the binding pocket not observed for alpha-conotoxin binding. Being in general very similar, the binding modes of short- and long alpha-neurotoxins differ in the ways of loop II entry into nAChR.
  Computational Biology and Chemistry 01/2006; 29(6):398-411. · 1.55 Impact Factor
• Article: A model for short alpha-neurotoxin bound to nicotinic acetylcholine receptor from

  D. Yu. Mordvintsev, Ya. L. Polyak, Olga V. Levtsova, Ye. V. Tourleigh, I. E. Kasheverov, K. V. Shaitan, Yu. N. Utkin, V. I. Tsetlin
  Computational Biology and Chemistry. 01/2005; 29:398-411.
• Article: Harmonic oscillators in the Nosé-Hoover environment.

  V L Golo, Vl N Salnikov, K V Shaitan
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  ABSTRACT: We study the dynamics of an ensemble of noninteracting harmonic oscillators in a nonlinear dissipative environment described by the Nosé-Hoover model, and find the histogram for energy regions of phase space against visiting time by employing numerical simulation. The results agree with the analysis of the Nosé-Hoover equations effected with the method of averaging for small values of the dissipative parameter alpha of the thermostat. We find oscillations at frequencies proportional to sqrt[alpha/m ], m being the characteristic mass of the particle, about the stationary state corresponding to equilibrium, for sufficiently small alpha . In this region of alpha the histogram does not correspond to Gibbs' canonical distribution. For larger values of alpha the motion becomes irregular. The phenomena could have an important bearing upon simulating molecular dynamics in the Nosé-Hoover thermostat.
  Physical Review E 11/2004; 70(4 Pt 2):046130. · 2.26 Impact Factor