Charles Matthews

Rational Construction of Stochastic Numerical Methods for Molecular Sampling

In this article, we focus on the sampling of the configurational Gibbs-Boltzmann distribution, that is, the calculation of averages of functions of the position coordinates of a molecular

The computation of averages from equilibrium and nonequilibrium Langevin molecular dynamics

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Robust and efficient configurational molecular sampling via Langevin dynamics.

-body system modelled at constant temperature. We show how a formal series expansion of the invariant measure of a Langevin dynamics numerical method can be obtained in a straightforward way using the Baker-Campbell-Hausdorff lemma. We then compare Langevin dynamics integrators in terms of their invariant distributions and demonstrate a superconvergence property (4th order accuracy where only 2nd order would be expected) of one method in the high friction limit; this method, moreover, can be reduced to a simple modification of the Euler-Maruyama method for Brownian dynamics involving a non-Markovian (coloured noise) random process. In the Brownian dynamics case, 2nd order accuracy of the invariant density is achieved. All methods considered are efficient for molecular applications (requiring one force evaluation per timestep) and of a simple form. In fully resolved (long run) molecular dynamics simulations, for our favoured method, we observe up to two orders of magnitude improvement in configurational sampling accuracy for given stepsize with no evident reduction in the size of the largest usable timestep compared to common alternative methods.

Molecular Dynamics: With Deterministic and Stochastic Numerical Methods

a la Talay-Tubaro on the invariant distribution for small stepsize, and compare the sampling bias obtained for various choices of splitting method. We further investigate the overdamped limit and apply the methods in the context of driven systems where the goal is sampling with respect to a non-equilibrium steady state. Our analyses are illustrated by numerical experiments.

Efficient molecular dynamics using geodesic integration and solvent-solute splitting.

A wide variety of numerical methods are evaluated and compared for solving the stochastic differential equations encountered in molecular dynamics. The methods are based on the application of deterministic impulses, drifts, and Brownian motions in some combination. The Baker-Campbell-Hausdorff expansion is used to study sampling accuracy following recent work by the authors, which allows determination of the stepsize-dependent bias in configurational averaging. For harmonic oscillators, configurational averaging is exact for certain schemes, which may result in improved performance in the modelling of biomolecules where bond stretches play a prominent role. For general systems, an optimal method can be identified that has very low bias compared to alternatives. In simulations of the alanine dipeptide reported here (both solvated and unsolvated), higher accuracy is obtained without loss of computational efficiency, while allowing large timestep, and with no impairment of the conformational exploration rate (the effective diffusion rate observed in simulation). The optimal scheme is a uniformly better performing algorithm for molecular sampling, with overall efficiency improvements of 25% or more in practical timestep size achievable in vacuum, and with reductions in the error of configurational averages of a factor of ten or more attainable in solvated simulations at large timestep.

On the long-time integration of stochastic gradient systems

1.Introduction.- 2.Numerical Integrators.- 3.Analyzing Geometric Integrators.- 4.The Stability Threshold.- 5.Phase Space Distributions and Microcanonical Averages.- 6. The Canonical Distribution and Stochastic Differential Equations.- 7. Numerical Methods for Stochastic Molecular Dynamics.- 8. Extended Variable Methods.- References.- Index.

Ensemble preconditioning for Markov chain Monte Carlo simulation

We present an approach to Langevin dynamics in the presence of holonomic constraints based on decomposition of the system into components representing geodesic flow, constrained impulse and constrained diffusion. We show that a particular ordering of the components results in an integrator that is an order of magnitude more accurate for configurational averages than existing alternatives. Moreover, by combining the geodesic integration method with a solvent–solute force splitting, we demonstrate that stepsizes of at least 8 fs can be used for solvated biomolecules with high sampling accuracy and without substantially altering diffusion rates, approximately increasing by a factor of two the efficiency of molecular dynamics sampling for such systems. The methods described in this article are easily implemented using the standard apparatus of modern simulation codes.

Numerical Methods for Stochastic Molecular Dynamics

This article addresses the weak convergence of numerical methods for Brownian dynamics. Typical analyses of numerical methods for stochastic differential equations focus on properties such as the weak order which estimates the asymptotic (stepsize h→0) convergence behaviour of the error of finite-time averages. Recently, it has been demonstrated, by study of Fokker–Planck operators, that a non-Markovian numerical method generates approximations in the long-time limit with higher accuracy order (second order) than would be expected from its weak convergence analysis (finite-time averages are first-order accurate). In this article, we describe the transition from the transient to the steady-state regime of this numerical method by estimating the time-dependency of the coefficients in an asymptotic expansion for the weak error, demonstrating that the convergence to second order is exponentially rapid in time. Moreover, we provide numerical tests of the theory, including comparisons of the efficiencies of the Euler–Maruyama method, the popular second-order Heun method, and the non-Markovian method.

Umbrella sampling: a powerful method to sample tails of distributions

We describe parallel Markov chain Monte Carlo methods that propagate a collective ensemble of paths, with local covariance information calculated from neighbouring replicas. The use of collective dynamics eliminates multiplicative noise and stabilizes the dynamics, thus providing a practical approach to difficult anisotropic sampling problems in high dimensions. Numerical experiments with model problems demonstrate that dramatic potential speedups, compared to various alternative schemes, are attainable.

The Canonical Distribution and Stochastic Differential Equations

In this chapter, we discuss principles for the design of algorithms for canonical sampling, based on the numerical discretization of stochastic dynamics models (such as Langevin dynamics) introduced in the previous chapter. Before we begin our discussion, let us consider the motivation for computing stationary averages using molecular dynamics.