Thermodynamics and kinetics of large-time-step molecular dynamics

Molecular dynamics (MD) simulations provide essential information about the thermodynamics and kinetics of proteins. Technological advances in both hardware and algorithms have seen this method accessing timescales that used to be unreachable only few years ago. The quest to simulate slow, biologically relevant macromolecular conformational changes, is still open. Here, we present an approximate approach to increase the speed of MD simulations by a factor of similar to 4.5. This is achieved by using a large integration time step of 7 fs, in combination with frozen covalent bonds and look-up tables for nonbonded interactions of the solvent. Extensive atomistic MD simulations for a flexible peptide in water show that the approach reproduces the peptide's equilibrium conformational changes, preserving the essential properties of both thermodynamics and kinetics. Comparison of this approximate method with state-of-the-art implicit solvation simulations indicates that the former provides a better description of the underlying free-energy surface. Finally, simulations of a 33-residue peptide show that these fast MD settings are readily applicable to investigate biologically relevant systems. (c) 2011 Wiley Periodicals, Inc.