Overcoming the Rare Event Sampling Problem in Biological Systems with Infinite Swapping.

Infinite swapping (INS) is a recently developed method to address the rare event sampling problem. For INS, an expanded computational ensemble composed of a number of replicas at different temperatures is used, similar to the widely used parallel tempering (PT) method. While the basic concept of PT is to sample various replicas of the system at different temperatures and exchange information between the replicas occasionally, INS uses the symmetrized distribution of configurations in temperature space, which corresponds to the infinite swapping limit of PT. The effect of this symmetrization and the enhanced information exchange between replicas is evaluated for three different biological systems representing different sampling problems in biology: (1) blocked alanine dipeptide, which is a small system and therefore optimal to evaluate sampling efficiency quantitatively, (2) Villin headpiece, which is used as a test case for the protein folding process, and (3) neuroglobin, which is used to evaluate the effects of enhanced information exchange between replicas for sampling the substate space of a folded protein. For these three test systems, PINS is compared to PT, and it is found that in all cases the sampling with PINS is substantially more efficient.