  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.
