Refining Multi-Scale Enhanced Sampling for Simulating Disordered Protein Conformations

Abstract

In the recently developed multiscale enhanced sampling (MSES) technique, topology-based coarse-grained (CG) models are coupled to atomistic protein force field to enhance the sampling of atomistic conformational space (Zhang and Chen, J. Chem Theory Comput, 2014). Here, we further refine the MSES protocol by designing more sophisticated Hamiltonian/temperature replica exchange schemes to more carefully control how the conformations are coupled between the atomistic and CG models, with a specific focus on optimizing the protocol for simulating disordered protein conformations. Preliminary results show that the new MSES protocols are effective in achieving better convergence in simulation of so-called intrinsically disordered proteins.