Dmitry E. Nolde


PeriodCountry, cityEducation institutionAdditional info
1986–1992 Russia, Moscow Region, g/ Dolgoprudny Moscow Institute of Physics and Technology

Selected publications

  1. Панина И.С., Нольде Д.Е., Чугунов А.О., Ефремов Р.Г. (2016). Структурно-динамическая модель комплекса лантибиотика низин с липидом-II в биомембране. Актуальные вопросы биологической физики и химии 1, 263–267 ID:1680
  2. Chugunov A.O., Volynsky P.E., Krylov N.A., Nolde D.E., Efremov R.G. (2016). Temperature-sensitive gating of TRPV1 channel as probed by atomistic simulations of its trans- and juxtamembrane domains. Sci Rep 6, 33112 [+]

    Heat-activated transient receptor potential channel TRPV1 is one of the most studied eukaryotic proteins involved in temperature sensation. Upon heating, it exhibits rapid reversible pore gating, which depolarizes neurons and generates action potentials. Underlying molecular details of such effects in the pore region of TRPV1 is of a crucial importance to control temperature responses of the organism. Despite the spatial structure of the channel in both open (O) and closed (C) states is known, microscopic nature of channel gating and mechanism of thermal sensitivity are still poorly understood. In this work, we used unrestrained atomistic molecular dynamics simulations of TRPV1 (without N- and C-terminal cytoplasmic domains) embedded into explicit lipid bilayer in its O- and C-states. We found that the pore domain with its neighboring loops undergoes large temperature-dependent conformational transitions in an asymmetric way, when fragments of only one monomer move with large amplitude, freeing the pore upon heating. Such an asymmetrical gating looks rather biologically relevant because it is faster and more reliable than traditionally proposed "iris-like" symmetric scheme of channel opening. Analysis of structural, dynamic, and hydrophobic organization of the pore domain revealed entropy growth upon TRPV1 gating, which is in line with current concepts of thermal sensitivity.

  3. Polyansky A.A., Chugunov A.O., Volynsky P.E., Krylov N.A., Nolde D.E., Efremov R.G. (2014). PREDDIMER: a web server for prediction of transmembrane helical dimers. Bioinformatics 30 (6), 889–90 [+]

    Here we present PREDDIMER, a web tool for prediction of dimer structure of transmembrane (TM) helices. PREDDIMER allows (i) reconstruction of a number of dimer structures for given sequence(s) of TM protein fragments, (ii) ranking and filtering of predicted structures according to respective values of a scoring function, (iii) visualization of predicted 3D dimer structures and (iv) visualization of surface hydrophobicity of TM helices and their contacting (interface) regions represented as 2D maps.

  4. Chugunov A., Pyrkova D., Nolde D., Polyansky A., Pentkovsky V., Efremov R. (2013). Lipid-II forms potential "landing terrain" for lantibiotics in simulated bacterial membrane. Sci Rep 3, 1678 [+]

    Bacterial cell wall is targeted by many antibiotics. Among them are lantibiotics, which realize their function via interaction with plasma membrane lipid-II molecule - a chemically conserved part of the cell wall synthesis pathway. To investigate structural and dynamic properties of this molecule, we have performed a series of nearly microsecond-long molecular dynamics simulations of lipid-II and some of its analogs in zwitterionic single component and charged mixed simulated phospholipid bilayers (the reference and the mimic of the bacterial plasma membrane, respectively). Extensive analysis revealed that lipid-II forms a unique "amphiphilic pattern" exclusively on the surface of the simulated bacterial membrane (and not in the reference one). We hypothesize that many lantibiotics exploit the conserved features of lipid-II along with characteristic modulation of the bacterial membrane as the "landing site". This putative recognition mechanism opens new opportunities for studies on lantibiotics action and design of novel armament against resistant bacterial strains.

  5. Чугунов А.О., Нольде Д.Е., Пыркова Д.В., Полянский А.А., Пентковский В.М., Ефремов Р.Г. (2013). На пути к новым антибиотикам. Суперкомпьютеры 12, 34–36 [+]

    Проблема резистентности бактерий к действию антибиотиков серьезна как никогда, и медицина всеми силами ищет пути к новым бактерицидным веществам, способным сохранять эффективность в течение долгих лет. Современная биофизика поможет ей в этом — наблюдение за молекулой антибиотика, которая «атакует» бактериальную клетку, подскажет ученым, как создать новые вещества, убивающие бактерий и безвредные для человеческого организма. Возможность для такого наблюдения дают суперкомпьютерные расчеты, а также современные физические модели и математические алгоритмы, предназначенные для изучения в вычислительном эксперименте структуры, динамики и функций сложнейших биологических супрамолекулярных систем. Исследователи из Института биоорганической химии РАН, используя ресурсы нового суперкомпьютера, установленного в лаборатории iScalare МФТИ, изучили на атомном уровне особенности организации мембраны бактерий, используя которые антибиотики преодолевают защитные системы клетки и оказывают антимикробное действие. Полученный результат указывает на возможность разработки нового поколения антибиотиков, избавленных от бремени резистентности.

  6. Pyrkova D.V., Tarasova N.K., Krylov N.A., Nolde D.E., Pentkovsky V.M., Efremov R.G. (2013). Dynamic clustering of lipids in hydrated two-component membranes: results of computer modeling and putative biological impact. J. Biomol. Struct. Dyn. 31 (1), 87–95 [+]

    Delineation and analysis of lateral clustering of lipids in model bilayers is an important step toward understanding of the physical processes underlying formation of lipid domains and rafts in cell membranes. Computer modeling methods represent a powerful tool to address the problem since they can detect clusters of only few lipid molecules - this issue still resists easy characterization with modern experimental techniques. In this work, we propose a computational method to detect and analyze parts of membrane with different packing densities and hydrogen bonding patterns. A series of one- and two-component fluid systems containing lipids with the same polar heads and different acyl chains, dioleoylphosphatidylcholine (18:1) and dipalmitoylphosphatidylcholine (16:0), or with same acyl chains and different polar heads, dioleoylphosphatidylserine (18:1) and dioleoylphosphatidylcholine (18:1), were studied via molecular dynamics simulations. Four criteria of clustering were considered. It was shown that the water-lipid interface of biomembranes represents a highly dynamic and "mosaic" picture, whose parameters depend on the bilayer composition. Some systems (e.g. with 20-30% of the anionic lipid) demonstrate unusual clustering properties and demand further investigation at molecular level. Lateral microheterogeneities in fluid lipid bilayers seem to be among the most important factors determining the nature of the membrane-water interface in a cell.

  7. Pyrkov T.V., Chugunov A.O., Krylov N.A., Nolde D.E., Efremov R.G. (2009). PLATINUM: a web tool for analysis of hydrophobic/hydrophilic organization of biomolecular complexes. Bioinformatics 25 (9), 1201–2 [+]

    The PLATINUM (Protein-Ligand ATtractions Investigation NUMerically) web service is designed for analysis and visualization of hydrophobic/hydrophilic properties of biomolecules supplied as 3D-structures. Furthermore, PLATINUM provides a number of tools for quantitative characterization of the hydrophobic/hydrophilic match in biomolecular complexes e.g. in docking poses. These complement standard scoring functions. The calculations are based on the concept of empirical Molecular Hydrophobicity Potential (MHP). AVAILABILITY: The PLATINUM web tool as well as detailed documentation and tutorial are available free of charge for academic users at PLATINUM requires Java 5 or higher and Adobe Flash Player 9. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

  8. Vereshaga Y.A., Volynsky P.E., Pustovalova J.E., Nolde D.E., Arseniev A.S., Efremov R.G. (2007). Specificity of helix packing in transmembrane dimer of the cell death factor BNIP3: a molecular modeling study. Proteins 69 (2), 309–25 [+]

    A computational technique for prediction of the spatial structure of transmembrane alpha-helical dimers is proposed. The approach is based on Monte Carlo simulations in the space of dihedral angles in the presence of the implicit membrane. Validity of the method was demonstrated with the example of transmembrane domain of mitochondrial pro-apoptotic protein BNIP3.

  9. Chugunov A.O., Novoseletsky V.N., Nolde D.E., Arseniev A.S., Efremov R.G. (2007). Method to assess packing quality of transmembrane alpha-helices in proteins. 1. Parametrization using structural data. Journal of chemical information and modeling 47 (3), 1150–62 [+]

    Integral membrane proteins (MPs) are pharmaceutical targets of exceptional importance. Modern methods of three-dimensional protein structure determination often fail to supply the fast growing field of structure-based drug design with the requested MPs' structures. That is why computational modeling techniques gain a special importance for these objects. Among the principal difficulties limiting application of these methods is the low quality of the MPs' models built in silico. In this series of two papers we present a computational approach to the assessment of the packing "quality" of transmembrane (TM) alpha-helical domains in proteins. The method is based on the concept of protein environment classes, whereby each amino acid residue is described in terms of its environment polarity and accessibility to the membrane. In the first paper we analyze a nonredundant set of 26 TM alpha-helical domains and compute the residues' propensities to five predefined classes of membrane-protein environments. Here we evaluate the proposed approach only by various test sets, cross-validation protocols and ability of the method to delimit the crystal structure of visual rhodopsin, and a number of its erroneous theoretical models. More advanced validation of the method is given in the second article of this series. We assume that the developed "membrane score" method will be helpful in optimizing computer models of TM domains of MPs, especially G-protein coupled receptors.

  10. Chugunov A.O., Novoseletsky V.N., Nolde D.E., Arseniev A.S., Efremov R.G. (2007). Method to assess packing quality of transmembrane alpha-helices in proteins. 2. Validation by "correct vs misleading" test. Journal of chemical information and modeling 47 (3), 1163–70 [+]

    We describe a set of tests designed to check the ability of the new "membrane score" method (see the first paper of this series) to assess the packing quality of transmembrane (TM) alpha-helical domains in proteins. The following issues were addressed: (1) Whether there is a relation between the score (S(mem)) of a model and its closeness to the "nativelike" conformation? (2) Is it possible to recognize a correct model among misfolded and erroneous ones? (3) To what extent the score of a homology-built model is sensitive to errors in sequence alignment? To answer the first question, two test cases were considered: (i) Several models of bovine aquaporin-1 (target protein) were built on the structural templates provided by its homologs with known X-ray structure. (ii) Side chains in the spatial models of visual rhodopsin and cytochrome c oxidase were rebuilt based on the backbone scaffolds taken from their crystal structures, and the resulting models were iteratively fitted into the full-atom X-ray conformations. It was shown that the higher the S(mem) value of a model is, the lower its root-mean-square deviation is from the "correct" (crystal) structure of a target. Furthermore, the "membrane score" method successfully identifies the rhodopsin crystal structure in an ensemble of "rotamer-type" decoys, thus providing the way to optimize mutual orientations of alpha-helices in models of TM domains. Finally, being applied to a set of homology models of rhodopsin built on its crystal structure with systematically shifted alignment, the approach demonstrates a prominent ability to detect alignment errors. We therefore assume that the "membrane score" method will be helpful in optimization of in silico models of TM domains in proteins, especially those in GPCRs.

  11. Volynsky P.E., Bocharov E.V., Nolde D.E., Vereshaga Y.A., Mayzel M.L., Mineev K.S., Mineeva E.V., Pustovalova Yu.E., Gagnidze I.A., Efremov R.G., Arseniev A.S. (2006). Solution of the Spatial Structure of Dimeric Transmembrane Domains of Proteins by Heteronuclear NMR Spectroscopy and Molecular Modeling. Biophysics 51 (S1), S23–S27 [+]

    Membrane proteins play an important role in various biological processes. An approach combining
    NMR spectroscopy with molecular modeling was used to study the spatial structure and intramolecular dynamics of protein transmembrane domains consisting of two interacting α-helices. The approach was tested with model transmembrane domains and yielded detailed atomic-level data on the protein–protein and protein–lipid interactions.

  12. Polyansky A.A., Volynsky P.E., Nolde D.E., Arseniev A.S., Efremov R.G. (2005). Role of lipid charge in organization of water/lipid bilayer interface: insights via computer simulations. The journal of physical chemistry. B 109 (31), 15052–9 [+]

    Anionic unsaturated lipid bilayers represent suitable model systems that mimic real cell membranes: they are fluid and possess a negative surface charge. Understanding of detailed molecular organization of water-lipid interfaces in such systems may provide an important insight into the mechanisms of proteins' binding to membranes. Molecular dynamics (MD) of full-atom hydrated lipid bilayers is one of the most powerful tools to address this problem in silico. Unfortunately, wide application of computational methods for such systems is limited by serious technical problems. They are mainly related to correct treatment of long-range electrostatic effects. In this study a physically reliable model of an anionic unsaturated bilayer of 1,2-dioleoyl-sn-glycero-3-phosphoserine (DOPS) was elaborated and subjected to long-term MD simulations. Electrostatic interactions were treated with two different algorithms: spherical cutoff function and particle-mesh Ewald summation (PME). To understand the role of lipid charge in the system behavior, similar calculations were also carried out for zwitterionic bilayer composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). It was shown that, for the charged DOPS bilayer, the PME protocol performs much better than the cutoff scheme. In the last case a number of artifacts in the structural organization of the bilayer were observed. All of them were attributed to inadequate treatment of electrostatic interactions of lipid headgroups with counterions. Electrostatic properties, along with structural and dynamic parameters, of both lipid bilayers were investigated. Comparative analysis of the MD data reveals that the water-lipid interface of the DOPC bilayer is looser than that for DOPS. This makes possible deeper penetration of water molecules inside the zwitterionic (DOPC) bilayer, where they strongly interact with carbonyls of lipids. This can lead to thickening of the membrane interface in zwitterionic as compared to negatively charged bilayers.

  13. Efremov R.G., Nolde D.E., Vergoten G., Arseniev A.S. (1999). A solvent model for simulations of peptides in bilayers. I. Membrane-promoting alpha-helix formation. Biophys. J. 76 (5), 2448–59 [+]

    A novel model of implicit membrane was proposed. The efficiency of the model in prediction of alpha-helical content of several homopolypeptides (poly-Leu, poly-Val, poly-Leu, poly-Gly) was proofed by series of Monte-Carlo simulations.

  14. Orekhov V.Y., Nolde D.E., Golovanov A.P., Korzhnev D.M., Arseniev A.S. (1995). Processing of heteronuclear NMR relaxation data with the new software DASHA. Appl. Mag. Reson. 9 (4), 581–588 [+]

    The new program DASHA is an efficient implementation of common data processing steps for the protein internal dynamic analysis. The “model-free” parameters and their uncertainties (Lipari G., Szabo A.: J. Am. Chem. Soc.104, 4546–4559 (1982) can be calculated from an arbitrary combination of experimental data sets (i.e. heteronuclear1H−15N or1H−13C relaxation times and NOE values at different spectrometer frequencies). Anisotropy of the molecular rotational diffusion could be also taken into account without introduction of the new adjustable parameters into the spectral density functionJ(ω), provided the structure of the molecule is known. Parameters of chemical (conformational) exchange can be estimated from the CPMG spin-lock frequency dependences (Bloomet al.: J. Chem. Phys.42, 1615–1624 (1965); Orekhovet al.: Eur. J. Biochem.219, 887–896 (1994). The program can be used both in the interactive and batch modes. It has sophisticated PostScript plotting facilities.