Conformational sampling of metastable states: Tq-REM as a novel replica exchange method.

ABSTRACT

Although the replica exchange methods (REMs) were developed as efficient conformational sampling methods for bio-molecular simulations, their application to very large bio-systems is somewhat limited. We propose a new replica exchange scheme (Tq-REM) created by combining the conventional temperature-REM (T-REM) and one of the Hamiltonian-REMs, q-REM, using the effective potential with reduced barriers. In the proposed Tq-REM scheme, high temperature replicas in T-REM are substituted with q-replicas. This combined scheme is expected to exploit advantages of the T-REM and q-REM resulting in improved sampling efficiency while minimizing the drawbacks of both approaches. We investigated the performance of Tq-REM compared with T-REM by performing all-atom MD simulations on Met-enkephalin, (AAQAA)3, and Trpzip2. It was found that convergence of the free energy surfaces was improved by Tq-REM over the conventional T-REM. In particular, the trajectories of Tq-REM were able to sample the relevant conformations for all of the metastable folding intermediates, while some of the local minimum structures are poorly represented by T-REM. The results of the present study suggest that Tq-REM can provide useful tools to investigate systems where metastable states play important roles.