Yevgeni Sh. Mamasakhlisov

Stacking and hydrogen bonding: DNA cooperativity at melting

By taking into account base–base stacking interactions we improve the Generalized Model of Polypeptide Chain (GMPC). Based on a one‐dimensional Potts‐like model with many‐particle interactions, the GMPC describes the helix–coil transition in both polypeptides and polynucleotides. In the framework of the GMPC we show that correctly introduced nearest‐neighbor stacking interactions against the background of hydrogen bonding lead to increased stability (melting temperature) and, unexpectedly, to decreased cooperativity (maximal correlation length). The increase in stability is explained as due to an additional stabilizing interaction (stacking) and the surprising decrease in cooperativity is seen as a result of mixing of contributions of hydrogen bonding and stacking.

Competition for hydrogen-bond formation in the helix-coil transition and protein folding

The problem of the helix-coil transition of biopolymers in explicit solvents, such as water, with the ability for hydrogen bonding with a solvent is addressed analytically using a suitably modified version of the Generalized Model of Polypeptide Chains. Besides the regular helix-coil transition, an additional coil-helix or reentrant transition is also found at lower temperatures. The reentrant transition arises due to competition between polymer-polymer and polymer-water hydrogen bonds. The balance between the two types of hydrogen bonding can be shifted to either direction through changes not only in temperature, but also by pressure, mechanical force, osmotic stress, or other external influences. Both polypeptides and polynucleotides are considered within a unified formalism. Our approach provides an explanation of the experimental difficulty of observing the reentrant transition with pressure and underscores the advantage of pulling experiments for studies of DNA. Results are discussed and compared with those reported in a number of recent publications with which a significant level of agreement is obtained.

Solvent effects in the helix-coil transition model can explain the unusual biophysics of intrinsically disordered proteins.

We analyze a model statistical description of the polypeptide chain helix-coil transition, where we take into account the specificity of its primary sequence, as quantified by the phase space volume ratio of the number of all accessible states to the number corresponding to a helical conformation. The resulting transition phase diagram is then juxtaposed with the unusual behavior of the secondary structures in Intrinsically Disordered Proteins (IDPs) and a number of similarities are observed, even if the protein folding is a more complex transition than the helix-coil transition. In fact, the deficit in bulky and hydrophobic amino acids observed in IDPs, translated into larger values of phase space volume, allows us to locate the region in parameter space of the helix-coil transition that would correspond to the secondary structure transformations that are intrinsic to conformational transitions in IDPs and that is characterized by a modified phase diagram when compared to globular proteins. Here, we argue how the nature of this modified phase diagram, obtained from a model of the helix-coil transition in a solvent, would illuminate the turned-out response of IDPs to the changes in the environment conditions that follow straightforwardly from the re-entrant (cold denaturation) branch in their folding phase diagram.

Theoretical treatment of helix–coil transition of complexes DNA with two different ligands having different binding parameters

The melting transition of DNA–ligand complexes, allowing for two binding mechanisms to different DNA conformations is treated theoretically. The obtained results express the behavior of the experimentally measurable quantities, degree of denaturation, and concentrations of bound ligands on the temperature. The range of binding parameters is obtained, where denaturation curves become multiphasic. The possible application to the nanocomposites crystallization is discussed.

192 The helix-coil transition in two-component solvent in the frames of GMPC. Ligands effects on the characteristics of the transition

(NC) contained within the capsid drives aggregation of both single-stranded (ss) gRNA and dsDNA, provided the capsid is intact. Flexible gRNA is aggregated by NC into a ribonucleoprotein complex occupying only a small fraction of the capsid volume. While the self-volume of the full-length pro-viral DNA (~10 bp) is the same as of its diploid gRNA genome, the dsDNA is very rigid, and gets condensed by NC into a large toroidal globule. We estimate that the weak dsDNA self-attraction induced by NC can lead to the size of the dsDNA globule similar to the size of the capsid. We predict very low value of mature capsid stability parameter for which it can be uncoated by pro-viral DNA condensed by NC. We describe the phase diagram that relates the volume of double stranded pro-viral DNA synthesized within the capsid, the strength of its NC-induced self-attraction, and the stability of the capsid at the point of uncoating. We discuss the current in vivo evidence for the relationship between the RTion and mature capsid uncoating in HIV.

191 Helix-coil transitions in heteropolymers: the constrained annealing approach

(NC) contained within the capsid drives aggregation of both single-stranded (ss) gRNA and dsDNA, provided the capsid is intact. Flexible gRNA is aggregated by NC into a ribonucleoprotein complex occupying only a small fraction of the capsid volume. While the self-volume of the full-length pro-viral DNA (~10 bp) is the same as of its diploid gRNA genome, the dsDNA is very rigid, and gets condensed by NC into a large toroidal globule. We estimate that the weak dsDNA self-attraction induced by NC can lead to the size of the dsDNA globule similar to the size of the capsid. We predict very low value of mature capsid stability parameter for which it can be uncoated by pro-viral DNA condensed by NC. We describe the phase diagram that relates the volume of double stranded pro-viral DNA synthesized within the capsid, the strength of its NC-induced self-attraction, and the stability of the capsid at the point of uncoating. We discuss the current in vivo evidence for the relationship between the RTion and mature capsid uncoating in HIV.

Kinetics of the long ssRNA: Steady state

The steady state in the kinetic pathways of the long single-strand RNA (ssRNA) in the approximation of a coarse-grained model is studied with analytic calculations. It is assumed that the characteristic time of the secondary-structure rearrangement is much longer than that for the formation of the tertiary structure. The entropy and the specific heat of the system as functions of the temperature are calculated and plotted. A non-equilibrium phase transition of the 2nd order has been observed. The possible biological implication of the obtained results is discussed.

Helix-coil transition in terms of Potts-like spins

In the spin model of a helix-coil transition in polypeptides a preferred value of spin has to be assigned to the helical conformation, in order to account for different symmetries of the helical vs. the coil states, leading thus to the Generalized Model of Polypeptide Chain (GMPC) Hamiltonian as opposed to the Potts model Hamiltonian, both with many-body interactions. Comparison of explicit transfer matrix secular equations of the Potts model and the GMPC model reveals that the largest eigenvalue of the Potts model with Δ many-body interactions coincides with the largest eigenvalue of the GMPC model with Δ − 1 many-body interactions, indicating the identity of both free energies. In distinction, the second largest eigenvalues in both models do not coincide, indicating a different behavior for the spatial correlation length that in its turn defines the width of the helix-coil transition interval. We explore in detail the thermodynamic consequences, resulting from spin models with and without the built-in spin anisotropy, that should indicate which model to favour as a more appropriate description of the equilibrium physical properties pertaining to the helix-coil transition.Graphical abstract

The double – stranded DNA stability in presence of a flexible polymer

The mixture of the short segments of double-stranded DNA and a flexible polymer are addressed. It is shown that in the condensed phase, rigid DNA molecules exhibit transition between isotropic and orientationally ordered phases. It is shown that orientational ordering stabilizes the secondary structure of double-stranded DNA that could be relevant for the regulation of the gene expression at the condensed state of DNA.

On the Performance and Energy Consumption of Molecular Dynamics Applications for Heterogeneous CPU-GPU Platforms Based on Gromacs

Abstract High Performance Computing (HPC) accelerates life science discoveries by enabling scientists to analyze large data sets, to develop detailed models of entire biological systems and to simulate complex biological processes. As computational experiments, molecular dynamics simulations are widely used in life sciences to evaluate the equilibrium nature of classical many-body systems The modelling and molecular dynamics study of surfactant, polymer solutions and the stability of proteins and nucleic acids under different conditions, as well as deoxyribonucleic acid proteins are studied. The study aims to understand the scaling behavior of Gromacs (Groningen machine for chemical simulations) on various platforms, and the maximum performance in the prospect of energy consumption that can be accomplished by tuning the hardware and software parameters. Different system sizes (48K, 64K, and 272K) from scientific investigations have been studied show that the GPU (Graphics Processing Unit) scales rather beneficial than other resources, i.e., with GPU support. We track 2-3 times speedup compared to the latest multi-core CPUs. However, the so-called “threading effect” leads to the better results.