182 research outputs found
An efficient Monte Carlo method for calculating ab initio transition state theory reaction rates in solution
In this article, we propose an efficient method for sampling the relevant
state space in condensed phase reactions. In the present method, the reaction
is described by solving the electronic Schr\"{o}dinger equation for the solute
atoms in the presence of explicit solvent molecules. The sampling algorithm
uses a molecular mechanics guiding potential in combination with simulated
tempering ideas and allows thorough exploration of the solvent state space in
the context of an ab initio calculation even when the dielectric relaxation
time of the solvent is long. The method is applied to the study of the double
proton transfer reaction that takes place between a molecule of acetic acid and
a molecule of methanol in tetrahydrofuran. It is demonstrated that calculations
of rates of chemical transformations occurring in solvents of medium polarity
can be performed with an increase in the cpu time of factors ranging from 4 to
15 with respect to gas-phase calculations.Comment: 15 pages, 9 figures. To appear in J. Chem. Phy
Configurational entropy, transition rates, and optimal interactions for rapid folding in coarse-grained model proteins
Under certain conditions, the dynamics of coarse-grained models of solvated
proteins can be described using a Markov state model, which tracks the
evolution of populations of configurations. The transition rates among states
that appear in the Markov model can be determined by computing the relative
entropy of states and their mean first passage times. In this paper, we present
an adaptive method to evaluate the configurational entropy and the mean first
passage times for linear chain models with discontinuous potentials. The
approach is based on event-driven dynamical sampling in a massively parallel
architecture. Using the fact that the transition rate matrix can be calculated
for any choice of interaction energies at any temperature, it is demonstrated
how each state's energy can be chosen such that the average time to transition
between any two states is minimized. The methods are used to analyze the
optimization of the folding process of two protein systems: the crambin
protein, and a model with frustration and misfolding. It is shown that the
folding pathways for both systems are comprised of two regimes: first, the
rapid establishment of local bonds, followed by the subsequent formation of
more distant contacts. The state energies that lead to the most rapid folding
encourage multiple pathways, and either penalize folding pathways through
kinetic traps by raising the energies of trapping states, or establish an
escape route from the trapping states by lowering free energy barriers to other
states that rapidly reach the native state
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