Removing Thermostat Distortions of Protein Dynamics in Constant-Temperature Molecular Dynamics Simulations.

Molecular dynamics simulations are widely used to determine equilibrium and dynamic properties of proteins. Nearly all simulations, currently, are carried out at constant temperature, with a Langevin thermostat among the most widely used. Thermostats distort protein dynamics, but whether or how such distortions can be corrected has long been an open question. Here, we show that constant-temperature simulations with a Langevin thermostat dilate protein dynamics and present a correction scheme to remove the dynamic distortions. Specifically, ns-scale time constants for overall rotation are dilated significantly but sub-ns time constants for internal motions are dilated modestly, while all motional amplitudes are unaffected. The correction scheme involves contraction of the time constants, with the contraction factor a linear function of the time constant to be corrected. The corrected dynamics of eight proteins are validated by NMR data for rotational diffusion and for backbone amide and side-chain methyl relaxation. The present work demonstrates that even for complex systems like proteins with dynamics spanning multiple timescales, one can predict how thermostats distort protein dynamics and remove such distortions. The correction scheme will have wide applications, facilitating force-field parameterization and propelling simulations to be on par with NMR and other experimental techniques in determining dynamic properties of proteins.