Self-assembly of a model supramolecular polymer studied by replica exchange with solute tempering

Abstract: Conventional molecular-dynamics (cMD) simulation has a well-known limitation in accessible time and length scales, and thus various enhanced sampling techniques have been proposed to alleviate the problem. In this paper we explore the utility of replica exchange with solute tempering (REST) (i.e., a variant of Hamiltonian replica exchange methods) to simulate the self-assembly of a supramolecular polymer in explicit solvent, and compare the performance with temperature-based replica exchange MD (T-REMD) as well as cMD. As a test system, we consider a relatively simple all-atom model of supramolecular polymerization (namely, benzene-1,3,5-tricarboxamides in methylcyclohexane solvent). Our results show that both REST and T-REMD are able to predict highly ordered polymer structures with helical H-bonding patterns, in contrast to cMD which completely fails to obtain such a structure for the present model. At the same time, we have also experienced some technical challenge (i.e., aggregation-dispersion transition and the resulting bottleneck for replica traversal), which is illustrated numerically. Since the computational cost of REST scales more moderately than T-REMD, we expect that REST will be useful for studying the self-assembly of larger systems in solution with enhanced rearrangement of monomers.