Frequency adaptive metadynamics for the calculation of rare-event kinetics

Abstract

The ability to predict accurate thermodynamic and kinetic properties in biomolecular systems is of both scientific and practical utility. While both remain very difficult, predictions of kinetics are particularly difficult because rates, in contrast to free energies, depend on the route taken and are thus not amenable to all enhanced sampling methods. It has recently been demonstrated that it is possible to recover kinetics through so called `infrequent metadynamics' simulations, where the simulations are biased in a way that minimally corrupts the dynamics of moving between metastable states. This method, however, requires the bias to be added slowly, thus hampering applications to processes with only modest separations of timescales. Here we present a frequency-adaptive strategy which bridges normal and infrequent metadynamics. We show that this strategy can improve the precision and accuracy of rate calculations at fixed computational cost, and should be able to extend rate calculations for much slower kinetic processes.

arXiv comment15 pages, 2 figures, 2 tables

References in corpus (7)

• Escaping free-energy minima
• PLUMED 2: New feathers for an old bird
• Well-Tempered Metadynamics: A Smoothly Converging and Tunable Free-Energy Method
• From Metadynamics to Dynamics
• The role of water and steric constraints in the kinetics of cavity-ligand unbinding
• Variationally Optimized Free Energy Flooding for Rate Calculation
• Efficient estimation of rare-event kinetics

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