Nikolay A. Krylov

Selected publications

  1. Konshina A.G., Krylov N.A., Efremov R.G. (2017). Cardiotoxins: Functional Role of Local Conformational Changes. Journal of chemical information and modeling 57 (11), 2799–2810 [+]

    Local conformational dynamics of rigid and highly stable membrane-active cardiotoxins (CTs) can seriously affect their functional activity. It has never been shown before that the local transformations of only a pair of residues can play a crucial role in membrane binding. Long-term molecular dynamics (MD) simulations and mapping of the conformational mobility of CTs (CT 1, 2 from Naja oxiana and CT A3 from Naja atra) in terms of backbone dihedrals φ / ψ transitions for every residue allowed delineation of specific “hot spots” in the protein structure - pair of residues K5/L6. This flexibility pattern is common to all studied CTs. The reversible large-scale transitions of backbone dihedrals in this locus result in corresponding breaking/association of the membrane-binding hydrophobic “bottom” on CTs surface (Figure). It assumes that interactions of the toxins with cell membranes are regulated by complementarity of surface hydrophobic/hydrophilic organization of the both partners.

  2. Kuzmenkov A.I., Krylov N.A., Chugunov A.O., Grishin E.V., Vassilevski A.A. (2016). Kalium: a database of potassium channel toxins from scorpion venom. Database (Oxford) 2016, [+]

    Kalium ( is a manually curated database that accumulates data on potassium channel toxins purified from scorpion venom (KTx). This database is an open-access resource, and provides easy access to pages of other databases of interest, such as UniProt, PDB, NCBI Taxonomy Browser, and PubMed. General achievements of Kalium are a strict and easy regulation of KTx classification based on the unified nomenclature supported by researchers in the field, removal of peptides with partial sequence and entries supported by transcriptomic information only, classification of β-family toxins, and addition of a novel λ-family. Molecules presented in the database can be processed by the Clustal Omega server using a one-click option. Molecular masses of mature peptides are calculated and available activity data are compiled for all KTx. We believe that Kalium is not only of high interest to professional toxinologists, but also of general utility to the scientific community.Database URL:

  3. 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.

  4. 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.

  5. Chugunov A.O., Volynsky P.E., Krylov N.A., Boldyrev I.A., Efremov R.G. (2014). Liquid but Durable: Molecular Dynamics Simulations Explain the Unique Properties of Archaeal-Like Membranes. Sci Rep 4, 7462 [+]

    Archaeal plasma membranes appear to be extremely durable and almost impermeable to water and ions, in contrast to the membranes of Bacteria and Eucaryota. Additionally, they remain liquid within a temperature range of 0-100°C. These are the properties that have most likely determined the evolutionary fate of Archaea, and it may be possible for bionanotechnology to adopt these from nature. In this work, we use molecular dynamics simulations to assess at the atomistic level the structure and dynamics of a series of model archaeal membranes with lipids that have tetraether chemical nature and "branched" hydrophobic tails. We conclude that the branched structure defines dense packing and low water permeability of archaeal-like membranes, while at the same time ensuring a liquid-crystalline state, which is vital for living cells. This makes tetraether lipid systems promising in bionanotechnology and material science, namely for design of new and unique membrane nanosystems.

  6. Krylov N.A., Pentkovsky V.M., Efremov R.G. (2013). Nontrivial behavior of water in the vicinity and inside lipid bilayers as probed by molecular dynamics simulations. ACS Nano 7 (10), 9428–42 [+]

    The atomic-scale diffusion of water in the presence of several lipid bilayers mimicking biomembranes is characterized via unconstrained molecular dynamics (MD) simulations. Although the overall water dynamics corresponds well to literature data, namely, the efficient braking near polar head groups of lipids, a number of interesting and biologically relevant details observed in this work have not been sufficiently discussed so far; for instance, the fact that waters "sense" the membrane unexpectedly early, before water density begins to decrease. In this "transitional zone" the velocity distributions of water and their H-bonding patterns deviate from those in the bulk solution. The boundaries of this zone are well preserved even despite the local (<1 nm size) perturbation of the lipid bilayer, thus indicating a decoupling of the surface and bulk dynamics of water. This is in excellent agreement with recent experimental data. Near the membrane surface, water movement becomes anisotropic, that is, solvent molecules preferentially move outward the bilayer. Deep in the membrane interior, the velocities can even exceed those in the bulk solvent and undergo large-scale fluctuations. The analysis of MD trajectories of individual waters in the middle part of the acyl chain region of lipids reveals a number of interesting rare phenomena, such as the fast (ca. 50 ps) breakthrough across the membrane or long-time (up to 750 ps) "roaming" between lipid leaflets. The analysis of these events was accomplished to delineate the mechanisms of spontaneous water permeation inside the hydrophobic membrane core. It was shown that such nontrivial dynamics of water in an "alien" environment is driven by the dynamic heterogeneities of the local bilayer structure and the formation of transient atomic-scale "defects" in it. The picture observed in lipid bilayers is drastically different from that in a primitive membrane mimic, a hydrated cyclohexane slab. The possible biological impact of such phenomena in equilibrated lipid bilayers is discussed.

  7. 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.

  8. Polyansky A.A., Vassilevski A.A., Volynsky P.E., Vorontsova O.V., Samsonova O.V., Egorova N.S., Krylov N.A., Feofanov A.V., Arseniev A.S., Grishin E.V., Efremov R.G. (2009). N-terminal amphipathic helix as a trigger of hemolytic activity in antimicrobial peptides: a case study in latarcins. FEBS Lett. 583 (14), 2425–8 [+]

    In silico structural analyses of sets of alpha-helical antimicrobial peptides (AMPs) are performed. Differences between hemolytic and non-hemolytic AMPs are revealed in organization of their N-terminal region. A parameter related to hydrophobicity of the N-terminal part is proposed as a measure of the peptide propensity to exhibit hemolytic and other unwanted cytotoxic activities. Based on the information acquired, a rational approach for selective removal of these properties in AMPs is suggested. A proof of concept is gained through engineering specific mutations that resulted in elimination of the hemolytic activity of AMPs (latarcins) while leaving the beneficial antimicrobial effect intact.

  9. 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.