Protein conformational fluctuations are highly complex and exhibit long-term correlations. Here, molecular dynamics simulations of small proteins demonstrate that these directly affect the protein's instantaneous diffusivity $D_I$. We find radius gyration $R_g$ exhibits $1/f$ fluctuations, synchronous with Our analysis demonstrates validity local Stokes-Einstein type relation $D_I\propto1/(R_g + R_0)$, where $R_0\sim0.3$ nm is assumed to be a hydration layer around protein. From different...

We apply moving root-mean-square deviation (mRMSD), which does not require a reference structure, as method for analyzing protein dynamics. This can be used to calculate the (RMSD) of structure between two specified time points and analyze dynamics behavior through series analysis. applied this Trp-cage trajectory calculated by Anton supercomputer found that it shows regions stable states well conventional RMSD. In addition, we extracted characteristic in side chains Asp1 Arg16 form hydrogen...

The replica-exchange multicanonical algorithm and the method for molecular dynamics simulations have recently been developed. In former weight factor is determined from a short simulation with multiple-histogram reweighting techniques. A long production run high statistics then performed this factor. method, process of determining faster simpler than that in usual iterative determination. further extension first which small number replicas. paper, we give formulations these two methods Monte...

We give general formulations of the multidimensional multicanonical algorithm, simulated tempering, and replica-exchange method. generalize original potential energy function E0 by adding any physical quantity V interest as a new term. These generalized-ensemble algorithms then perform random walk not only in space but also space. Among three algorithms, method is easiest to because weight factor just product regular Boltzmann-like factors, while factors for algorithm tempering are priori...

This article reports the first attempt to apply relaxation mode analysis method a simulation of biomolecular system. In systems, principal component is well-known for analyzing static properties fluctuations structures obtained by and classifying into some groups. On other hand, has been used analyze dynamic homopolymer systems. this article, long Monte Carlo Met-enkephalin in gas phase performed. The results are analyzed methods. We compare both methods show effectiveness analysis.

In Paper I of this series the formulations replica-exchange multicanonical algorithm and method for Monte Carlo versions have been presented. The effectiveness these algorithms were then tested with system a penta peptide, Met-enkephalin, in gas phase. article detailed comparisons performances together regular are made, taking more complex 17-residue helical peptide. It is shown that two new efficient than method.

In this paper we consider combinations of two well-known generalized-ensemble algorithms, namely, simulated tempering and replica-exchange method. We discuss examples such combinations. One is the other former method, a short simulation first performed weight factor obtained by multiple-histogram reweighting techniques. This process determination faster simpler than that in usual iterative process. A long production run then with factor. The latter method further extension which small number...

We discuss multidimensional generalizations of multicanonical algorithm, simulated tempering, and replica-exchange method. generalize the original potential-energy function ${E}_{0}$ by adding any physical quantity $V$ interest as a new energy term with coupling constant $\ensuremath{\lambda}$. then perform simulation where random walk in spaces is realized. can alternately simulated-tempering temperature $T$ parameter $\ensuremath{\lambda}$ The results simulations be used to determine...

It is important to extract reaction coordinates or order parameters from protein simulations in investigate the local minimum-energy states and transitions between them. The most popular method obtain such data principal component analysis, which extracts modes of large conformational fluctuations around an average structure. We recently applied relaxation mode analysis for systems, approximately estimates slow times a simulation enables investigations dynamic properties underlying...

The three-dimensional reference interaction site model (3D-RISM) theory, which is one of the most applicable integral equation theories for molecular liquids, overestimates absolute values solvation-free-energy (SFE) large solute molecules in water. To improve free-energy density functional SFE molecules, we propose a reference-modified theory (RMDFT) that general theoretical approach to construct systematically. In RMDFT formulation, hard-sphere (HS) fluids are introduced as system instead...

We devise a new computational approach to compute solid-liquid phase equilibria of confined fluids. Specifically, we extend the multibaric-multithermal ensemble method with an anisotropic pressure control achieve equilibrium for water inside slit nanopores (with width h ranging from 5.4 Å 7.2 Å). A unique feature this is that freezing points can be determined heat-capacity peaks. The has been applied point two monolayer ices, namely, high-density flat rhombic ice (HD-fRMI) and puckered...

Liquid-solid and solid-solid phase transitions of a monolayer water confined between two parallel hydrophobic surfaces are studied by molecular dynamics simulations. The solid considered is the high-density rhombic ice. Based on computed free energy surface, it found that at certain width slit nanopore, exhibits not only high freezing point but also low barrier to crystallization. Moreover, through analyzing oxygen-hydrogen-oxygen angle distribution oxygen-hydrogen radial distribution, ice...

Helix-coil transitions of homo-oligomers in aqueous solution are studied by multicanonical Monte Carlo simulations. The solvation effects represented the sum terms that proportional to solvent-accessible surface area atomic groups. Homo-oligomers length 10 considered for three characteristic amino acids, alanine, valine, and glycine, which helix former, indifferent, breaker, respectively. We calculated as a function temperature distributions backbone dihedral angles, average values total...

In this article, the general formulation of multidimensional simulated-tempering replica-exchange method is described. previous works, one-dimensional and methods were developed. For former method, weight factor simulated tempering determined by a short simulation multiple-histogram reweighing techniques. latter production run with few replicas not in canonical ensembles but which cover wide ranges temperature. Recently, was presented. extension for version given. As an example applications...

Protein stability is determined by the characteristics of protein itself as well surrounding solvent. Herein, we discuss folded and unfolded structures proteins obtained from Anton's long simulations (Lindorff-Larsen, K.; Piana, S.; Dror, R. O.; Shaw, D.E. Science, 2011, 334, 517-520). Specifically, stabilities CLN025, WW domain variant GTT, triple mutant redesigned G NuG2, de novo-designed three-helix bundle are investigated. The solvation free energy calculated using three-dimensional...

We simulate the nonequilibrium ensemble dynamics of a biomolecule using weighted method, which was introduced in molecular simulations by Huber and Kim further developed Zuckerman co-workers. As order parameters to characterize its conformational change, we here use coordinates derived from diffusion map (DM) one manifold learning techniques. concrete example, study kinetic properties small peptide, chignolin explicit water, calculate change between folded misfolded states way. find that...

A new relaxation mode analysis method, which is referred to as the principal component has been proposed handle a large number of degrees freedom protein systems. In this carried out first and then applied small components with fluctuations. To reduce contribution fast modes in these efficiently, we have also method using multiple evolution times. The two times an all-atom molecular dynamics simulation human lysozyme aqueous solution. Slow corresponding appropriately estimated, demonstrating...

This article reports the first attempt to combine replica-exchange Monte Carlo method and reference interaction site model (RISM) theory for simulating a peptide molecule in aqueous solution. The energy function is sum of conformational solvation free energy. fixed conformation calculated using RISM theory. modified so that dependence on temperature can be incorporated. effectiveness combined approach demonstrated Met-enkephalin water. It argued number replicas required immersed water...

We investigate melting behavior of water clusters (H2O)N (N = 7, 8, 11, and 12) by using multicanonical-ensemble molecular dynamics simulations. Our simulations show that the is highly size dependent. Based on computed canonical average potential energy heat capacity CV, we conclude (H2O)8 (H2O)12 exhibit first-order-like phase change, while (H2O)7 (H2O)11 continuous-like change. The temperature range for can be defined based peak position CV(T) dCV(T)/dT (where T temperature). Moreover,...

We discuss the stability of an entire protein and influence main chains side individual amino acids to investigate protein-folding mechanism. For this purpose, we calculated solvation free-energy contribution atoms using three-dimensional reference interaction site model with atomic decomposition method. generated structures chignolin miniprotein by a molecular dynamics simulation classified them into six types: native 1, 2, misfolded intermediate, unfolded states. The total energies (−171.1...