TCB Publications - Abstract

Justin Gullingsrud, Rosemary Braun, and Klaus Schulten. Reconstructing potentials of mean force through time series analysis of steered molecular dynamics simulations. Journal of Computational Physics, 151:190-211, 1999.

GULL99 Atomic force microscopy (AFM) experiments and Steered Molecular Dynamics (SMD) simulations have revealed much about the dynamics of protein-ligand binding and unbinding. Both techniques induce ligand unbinding by applying external mechanical forces to the ligand. However, comparing results from these two techniques, such as the magnitude of forces required to unbind ligands, has remained a challenge since SMD simulations proceed six to nine orders of magnitude faster due to limitations in computational resources. One way results of simulations and experiments can be compared is through a potential of mean force (PMF). We describe and implement three time series analysis techniques for reconstructing the PMF from position and applied force data gathered from SMD trajectories. One method, based on the WHAM theory, views the unbinding as a quasi-equilibrium process; the other two, one based on van Kampen's $\Omega$-expansion, the second on a least squares minimization of the Onsager-Machlup action with respect to the choice of PMF, assume a Langevin description of the dynamics in order to account for the nonequilibrium character of SMD data. The van Kampen and least squares methods are applied to SMD data taken from a simulation of the extraction of a lipid from a phospholipid membrane monolayer.

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