Dissociation aided and side chain sampling enhanced Hamiltonian replica exchange

A new application of Hamiltonian replica exchange method is suggested: The potential energy function is adjusted in such a way that repulsive forces between atoms of solute are reinforced. This dissociation action helps the system to escape from the local minima on the free energy landscape. Compared with other Hamiltonian replica exchange methods in which the potential energy between solute atoms and between solute and solvent atoms was reduced, and compared with the temperature replica exchange method, the new scheme displays superior ability to overcome large free energy barrier in a model system. For protein simulation, the side chain conformation sampling turns out to be an issue and an enhancement method is introduced. Combining the dissociation aided method with the specific side chain sampling technique is proven to be a help to explore the complex energy landscape of protein, which is demonstrated by three independent ab initio folding simulations on the trpzip2 peptide. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3120483]