Adaptive time stepping in biomolecular dynamics.

Abstract

We present an adaptive time stepping scheme based on the extrapolative method of Barth and Schlick [LN, J. Chem. Phys. 109, 1633 (1998)] to numerically integrate the Langevin equation with a molecular-dynamics potential. This approach allows us to use (on average) a time step for the strong nonbonded force integration corresponding to half the period of the fastest bond oscillation, without compromising the slow degrees of freedom in the problem. We show with simple examples how the dynamic step size stabilizes integration operators, and discuss some of the limitations of such stability. The method introduced uses a slightly more accurate inner integrator than LN to accommodate the larger steps. The adaptive time step approach reproduces temporal features of the bovine pancreatic trypsin inhibitor (BPTI) test system (similar to the one used in the original introduction of LN) compared to short-time integrators, but with energies that are shifted with respect to both LN, and traditional stochastic versions of Verlet. Although the introduction of longer steps has the effect of systematically heating the bonded components of the potential, the temporal fluctuations of the slow degrees of freedom are reproduced accurately. The purpose of this paper is to display a mechanism by which the resonance traditionally associated with using time steps corresponding to half the period of oscillations in molecular dynamics can be avoided. This has theoretical utility in terms of designing numerical integration schemes--the key point is that by factoring a propagator so that time steps are not constant one can recover stability with an overall (average) time step at a resonance frequency. There are, of course, limitations to this approach associated with the complicated, nonlinear nature of the molecular-dynamics (MD) potential (i.e., it is not as straightforward as the linear test problem we use to motivate the method). While the basic notion remains in the full Newtonian problem, it is easier to see the effects when damping is considered to be physical--that is, we do not view our method as a perturbation of Newtonian dynamics, we associate the damping with the environment, for example, a water bath (with gamma approximately 90 ps(-1)) [Zagrovic and Pande, J. Comp. Chem. 24, 1432 (2003)]. All stochastic approaches to MD are stabilized by large physical damping, but here, we are really using it only to show that the resonance frequency can be obtained. Another simplifying assumption used in this paper is "heavy" hydrogen (we take the hydrogen mass to be 10 amu)--the view here is that we are interested primarily in the slowest degrees of freedom, and this approach has effects similar to bond freezing and united atom treatments of hydrogen. So from the point of view of biomolecular applications, the method described here is best suited to studies in which water is not explicit (so that damping in the problem can really be viewed as environmental interaction), and the interest is in slow dynamics where the effects of hydrogen are neglectable. There are a number of parameters in the LN method and the one derived here, and we cannot in a short paper address all adjustments, so our primary goal as a first pass is to show that stability can be recovered for a set of numerically forced (and hence artificial) bond oscillations, and compare stability to fixed-step methods.