Multi-dimensional virtual system introduced to enhance canonical sampling

J Chem Phys. 2017 Oct 7;147(13):134102. doi: 10.1063/1.4986129.


When an important process of a molecular system occurs via a combination of two or more rare events, which occur almost independently to one another, computational sampling for the important process is difficult. Here, to sample such a process effectively, we developed a new method, named the "multi-dimensional Virtual-system coupled Monte Carlo (multi-dimensional-VcMC)" method, where the system interacts with a virtual system expressed by two or more virtual coordinates. Each virtual coordinate controls sampling along a reaction coordinate. By setting multiple reaction coordinates to be related to the corresponding rare events, sampling of the important process can be enhanced. An advantage of multi-dimensional-VcMC is its simplicity: Namely, the conformation moves widely in the multi-dimensional reaction coordinate space without knowledge of canonical distribution functions of the system. To examine the effectiveness of the algorithm, we introduced a toy model where two molecules (receptor and its ligand) bind and unbind to each other. The receptor has a deep binding pocket, to which the ligand enters for binding. Furthermore, a gate is set at the entrance of the pocket, and the gate is usually closed. Thus, the molecular binding takes place via the two events: ligand approach to the pocket and gate opening. In two-dimensional (2D)-VcMC, the two molecules exhibited repeated binding and unbinding, and an equilibrated distribution was obtained as expected. A conventional canonical simulation, which was 200 times longer than 2D-VcMC, failed in sampling the binding/unbinding effectively. The current method is applicable to various biological systems.