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Papers by Sergei Chekmarev
The Journal of Physical Chemistry B, 2013
A new analysis of the 20 μs equilibrium folding/unfolding molecular dynamics simulations of the t... more A new analysis of the 20 μs equilibrium folding/unfolding molecular dynamics simulations of the three-stranded antiparallel β-sheet miniprotein (beta3s) in implicit solvent is presented. The conformation space is reduced in dimensionality by introduction of linear combinations of hydrogen bond distances as the collective variables making use of a specially adapted principal component analysis (PCA); i.e., to make structured conformations more pronounced, only the formed bonds are included in determining the principal components. It is shown that a three-dimensional (3D) subspace gives a meaningful representation of the folding behavior. The first component, to which eight native hydrogen bonds make the major contribution (four in each beta hairpin), is found to play the role of the reaction coordinate for the overall folding process, while the second and third components distinguish the structured conformations. The representative points of the trajectory in the 3D space are grouped into conformational clusters that correspond to locally stable conformations of beta3s identified in earlier work. A simplified kinetic network based on the three components is constructed, and it is complemented by a hydrodynamic analysis. The latter, making use of "passive tracers" in 3D space, indicates that the folding flow is much more complex than suggested by the kinetic network. A 2D representation of streamlines shows there are vortices which correspond to repeated local rearrangement, not only around minima of the free energy surface but also in flat regions between minima. The vortices revealed by the hydrodynamic analysis are apparently not evident in folding pathways generated by transition-path sampling. Making use of the fact that the values of the collective hydrogen bond variables are linearly related to the Cartesian coordinate space, the RMSD between clusters is determined. Interestingly, the transition rates show an approximate exponential correlation with distance in the hydrogen bond subspace. Comparison with the many published studies shows good agreement with the present analysis for the parts that can be compared, supporting the robust character of our understanding of this "hydrogen atom" of protein folding.
Physical Review Letters, 2008
A hydrodynamic description of protein folding is proposed and illustrated with a lattice protein ... more A hydrodynamic description of protein folding is proposed and illustrated with a lattice protein model, which has a free energy surface (FES) typical of proteins with two-state folding kinetics. The flows from the unfolded to the native state are concentrated in a limited region of the FES. The rest is occupied by a flow "vortex", which does not lead to the native state. In contrast with intermediates that are associated with local minima, the vortex is not visible on the FES. The hydrodynamic interpretation thus provides new insights into the mechanism of protein folding and can be a useful complement to standard analyses.
Combustion, Explosion, and Shock Waves, 1985
The movement of detonation products and ambient gas after detonation of a linear explosive charge... more The movement of detonation products and ambient gas after detonation of a linear explosive charge in the atmosphere is investigated. Main attention is devoted to flow at large distances from the detonation wave (much greater than the charge radius). Flow was investigated earlier in [1] with respect to the propagation of shock waves in the atmosphere during movement of meteorites, initiation of detonation in other media, and determination of the effect on the walls of an explosion chamber. In these works mainly movement of the shock wave in the atmosphere (in air) was studied and the movement of the detonation products themselves were ha=dly considered. The principal of energy similarity [i] was used for describing the dependence of the characteristics of the shock wave on the properties of the explosives. In the present work, which is a continuation of , experimental data are obtained on the movement of shock waves in anatmosphere of various gases (air, helium, argon) and at various pressures, and also on the movement of the detonation products themselves, in particular, their boundary. The jet analogy [4] is used for analyzing flow similarity, which makes it possible to establish the properties of flow similarity as a whole. The conclusions about flow similarity are illustrated by experimental data. The relation of flow similarity is discussed on the basis of the energy principle and jet analogy.
Combustion, Explosion, and Shock Waves, 1981
The Journal of Physical Chemistry B, 2007
We have designed a model lattice protein that has two stable folded states, the lower free energy... more We have designed a model lattice protein that has two stable folded states, the lower free energy native state and a latent state of somewhat higher energy. The two states have a sizable part of their structures in common (two "alpha-helices") and differ in the content of "alpha-helices" and "beta-strands" in the rest of their structures; i.e. for the native state, this part is alpha-helical, and for the latent state it is composed of beta-strands. Thus, the lattice protein free energy surface mimics that of amyloidogenic proteins that form well organized fibrils under appropriate conditions. A Go-like potential was used and the folding process was simulated with a Monte Carlo method. To gain insight into the equilibrium free energy surface and the folding kinetics, we have combined standard approaches (reduced free energy surfaces, contact maps, time-dependent populations of the characteristic states, and folding time distributions) with a new approach. The latter is based on a principal coordinate analysis of the entire set of contacts, which makes possible the introduction of unbiased reaction coordinates and the construction of a kinetic network for the folding process. The system is found to have four characteristic basins, namely a semicompact globule, an on-pathway intermediate (the bifurcation basin), and the native and latent states. The bifurcation basin is shallow and consists of the structure common to the native and latent states, with the rest disorganized. On the basis of the simulation results, a simple kinetic model describing the transitions between the characteristic states was developed, and the rate constants for the essential transitions were estimated. During the folding process the system dwells in the bifurcation basin for a relatively short time before it proceeds to the native or latent state. We suggest that such a bifurcation may occur generally for proteins in which native and latent states have a sizable part of their structures in common. Moreover, there is the possibility of introducing changes in the system (e.g., mutations), which guide the system toward the native or misfolded state.
The Journal of Physical Chemistry B, 2013
A new analysis of the 20 μs equilibrium folding/unfolding molecular dynamics simulations of the t... more A new analysis of the 20 μs equilibrium folding/unfolding molecular dynamics simulations of the three-stranded antiparallel β-sheet miniprotein (beta3s) in implicit solvent is presented. The conformation space is reduced in dimensionality by introduction of linear combinations of hydrogen bond distances as the collective variables making use of a specially adapted principal component analysis (PCA); i.e., to make structured conformations more pronounced, only the formed bonds are included in determining the principal components. It is shown that a three-dimensional (3D) subspace gives a meaningful representation of the folding behavior. The first component, to which eight native hydrogen bonds make the major contribution (four in each beta hairpin), is found to play the role of the reaction coordinate for the overall folding process, while the second and third components distinguish the structured conformations. The representative points of the trajectory in the 3D space are grouped into conformational clusters that correspond to locally stable conformations of beta3s identified in earlier work. A simplified kinetic network based on the three components is constructed, and it is complemented by a hydrodynamic analysis. The latter, making use of "passive tracers" in 3D space, indicates that the folding flow is much more complex than suggested by the kinetic network. A 2D representation of streamlines shows there are vortices which correspond to repeated local rearrangement, not only around minima of the free energy surface but also in flat regions between minima. The vortices revealed by the hydrodynamic analysis are apparently not evident in folding pathways generated by transition-path sampling. Making use of the fact that the values of the collective hydrogen bond variables are linearly related to the Cartesian coordinate space, the RMSD between clusters is determined. Interestingly, the transition rates show an approximate exponential correlation with distance in the hydrogen bond subspace. Comparison with the many published studies shows good agreement with the present analysis for the parts that can be compared, supporting the robust character of our understanding of this "hydrogen atom" of protein folding.
Physical Review Letters, 2008
A hydrodynamic description of protein folding is proposed and illustrated with a lattice protein ... more A hydrodynamic description of protein folding is proposed and illustrated with a lattice protein model, which has a free energy surface (FES) typical of proteins with two-state folding kinetics. The flows from the unfolded to the native state are concentrated in a limited region of the FES. The rest is occupied by a flow "vortex", which does not lead to the native state. In contrast with intermediates that are associated with local minima, the vortex is not visible on the FES. The hydrodynamic interpretation thus provides new insights into the mechanism of protein folding and can be a useful complement to standard analyses.
Combustion, Explosion, and Shock Waves, 1985
The movement of detonation products and ambient gas after detonation of a linear explosive charge... more The movement of detonation products and ambient gas after detonation of a linear explosive charge in the atmosphere is investigated. Main attention is devoted to flow at large distances from the detonation wave (much greater than the charge radius). Flow was investigated earlier in [1] with respect to the propagation of shock waves in the atmosphere during movement of meteorites, initiation of detonation in other media, and determination of the effect on the walls of an explosion chamber. In these works mainly movement of the shock wave in the atmosphere (in air) was studied and the movement of the detonation products themselves were ha=dly considered. The principal of energy similarity [i] was used for describing the dependence of the characteristics of the shock wave on the properties of the explosives. In the present work, which is a continuation of , experimental data are obtained on the movement of shock waves in anatmosphere of various gases (air, helium, argon) and at various pressures, and also on the movement of the detonation products themselves, in particular, their boundary. The jet analogy [4] is used for analyzing flow similarity, which makes it possible to establish the properties of flow similarity as a whole. The conclusions about flow similarity are illustrated by experimental data. The relation of flow similarity is discussed on the basis of the energy principle and jet analogy.
Combustion, Explosion, and Shock Waves, 1981
The Journal of Physical Chemistry B, 2007
We have designed a model lattice protein that has two stable folded states, the lower free energy... more We have designed a model lattice protein that has two stable folded states, the lower free energy native state and a latent state of somewhat higher energy. The two states have a sizable part of their structures in common (two "alpha-helices") and differ in the content of "alpha-helices" and "beta-strands" in the rest of their structures; i.e. for the native state, this part is alpha-helical, and for the latent state it is composed of beta-strands. Thus, the lattice protein free energy surface mimics that of amyloidogenic proteins that form well organized fibrils under appropriate conditions. A Go-like potential was used and the folding process was simulated with a Monte Carlo method. To gain insight into the equilibrium free energy surface and the folding kinetics, we have combined standard approaches (reduced free energy surfaces, contact maps, time-dependent populations of the characteristic states, and folding time distributions) with a new approach. The latter is based on a principal coordinate analysis of the entire set of contacts, which makes possible the introduction of unbiased reaction coordinates and the construction of a kinetic network for the folding process. The system is found to have four characteristic basins, namely a semicompact globule, an on-pathway intermediate (the bifurcation basin), and the native and latent states. The bifurcation basin is shallow and consists of the structure common to the native and latent states, with the rest disorganized. On the basis of the simulation results, a simple kinetic model describing the transitions between the characteristic states was developed, and the rate constants for the essential transitions were estimated. During the folding process the system dwells in the bifurcation basin for a relatively short time before it proceeds to the native or latent state. We suggest that such a bifurcation may occur generally for proteins in which native and latent states have a sizable part of their structures in common. Moreover, there is the possibility of introducing changes in the system (e.g., mutations), which guide the system toward the native or misfolded state.