In accelerated molecular dynamics (aMD), a bias potential is applied to the original Hamiltonian to increase conformational sampling. Equilibrium properties of the original free energy landscape can be retrieved after correcting for the bias. Similarly, original kinetics can be obtained by reweighting time, provided transition state regions are not modified upon adding the bias. However, for biomolecular systems with multi-dimensional landscape, this condition is almost never met, resulting in inaccurate estimation of kinetics. We show that by carrying out aMD in explicit solvent at a couple of different levels and using Kramers' theory in the high friction regime, we can circumvent the parameter-dependent time-reweighting problem. Employing this approach in combination with the revised omega torsional AMBER parameters, we can obtain normal cis-trans isomerization rates in protein-like peptides that closely agree to experimental estimates. Our approach is highly amenable for studying kinetics of activated processes occurring on the very slow minutes-timescale.

Parameter optimization and extraction of realistic kinetics for peptide bond isomerization

243rd National Meeting (2012)

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