(168f) On-the-Fly Free-Energy Parameterization Using Temperature-Accelerated MD

We discuss a method for parametric calculation of free energy functions in arbitrary collective variables using molecular simulations.  The method, termed “on-the-fly paramterization (OTFP)” fits the framework of the heterogeneous multiscale method and uses a variant of temperature accelerated molecular dynamics (TAMD [1]) to evolve the parameters of any free energy function to optimum values by minimization of a cumulative gradient error.  We first illustrate how the method performs using simple examples that prove the underlying assumptions of TAMD, most importantly that it accurately reports free-energy gradients while exploring collective variable space.  As practical examples, we show how OTFP can be used to derive coarse-grained pairwise effective potentials for systematic coarse-graining.  In particular we compare effective potentials derived for coarse-grained water with those derived using force-matching [2] and minimization of relative entropy [3].  OTFP may be slightly advantageous because the acceleration afforded by TAMD can provide statistics more efficiently than the thermal ensemble-averaging approaches used by the other methods.

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2.            Izvekov, S. and G.A. Voth, A multiscale coarse-graining method for biomolecular systems. Journal of Physical Chemistry B, 2005. 109(7): p. 2469-2473.

3.            Chaimovich, A. and M.S. Shell, Anomalous waterlike behavior in spherically-symmetric water models optimized with the relative entropy. Physical Chemistry Chemical Physics, 2009. 11(12): p. 1901-1915.