Conformational transition pathway and free energy analyses of proteins by parallel cascade selection molecular dynamics (PaCS-MD)

Abstract

Parallel Cascade Selection Molecular Dynamics (PaCS-MD) was recently proposed to generate conformational transition pathways of proteins under the condition that a certain target quantity to be reached is introduced (R. Harada and A. Kitao, J. Chem. Phys., 139, 035103 2013). In PaCS-MD, the cycle of short multiple independent molecular dynamics simulations and selection of the structures close to the target quantity for the next cycle are repeated until the simulated structures move sufficiently close to the target. Conformational sampling efficiency is demonstrated in the cases of mini-protein folding/unfolding and protein large conformational transitions. The result of PaCS-MD was further utilized to calculate free energy landscape by the combination with weighted-histogram analysis method or Markov state model.