Repeated-annealing sampling combined with multicanonical algorithm for conformational sampling of bio-molecules

A novel conformational sampling method (repeated-annealing sampling method) is proposed to execute an efficient conformational sampling at a reasonable computational cost. In the method, a molecular dynamics simulation is done with repeating an elemental process. An elemental process consists of four subprocesses: high-temperature run, annealing, room-temperature run, and fast heating. The sampling is done automatically according to a temperature-control schedule. The room-temperature run is treated with the multicanonical algorithm, and the other subprocesses are done with the conventional molecular dynamics algorithm. The method, differing from the generalized ensemble methods recently developed, is not warrantable to give the canonical ensemble because of the nonphysical process in the annealing. However, we observed that the slower the annealing and the longer the high-temperature run, the closer the sampled conformations to those of the canonical ensemble. A test was performed with tri-N-acetyl-D-glucosamine in vacuo, and the results were compared with those from the conventional multicanonical simulation. Not only the reweighted canonical distribution function but also the energy landscape were in good agreement with those from the conventional multicanonical simulation. The potential of mean force also showed a fairly good agreement with that from the conventional multicanonical simulation in the room-temperature region. (C) 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1098-1106, 2001.