A restrained locally enhanced sampling method (RLES) for finding free energy minima in complex systems

Victor Ovchinnikov, Simone Conti, and Martin Karplus

The Journal of Chemical Physics, 2020, 153, pp 121103.
DOI:10.1063/5.0018026 | Find on RG

Abstract:

We present an extension of the locally enhanced sampling method. A restraint potential is introduced to drive the many-replica system to the canonical ensemble corresponding to the physical, single-replica system. Convergence properties are demonstrated using a model rugged two-dimensional potential, for which sampling by conventional equilibrium molecular dynamics is inefficient. Restrained locally enhanced sampling (RLES) is found to explore the space of configurations with an efficiency comparable to that of temperature replica exchange. To demonstrate the potential of RLES for realistic applications, the method is used to fold the 12-residue tryptophan zipper miniprotein in explicit solvent. The RLES algorithm can be incorporated into existing LES implementations with minor code modifications.