The multicanonical weighted histogram analysis method for the free-energy landscape along structural transition paths

A new algorithm for revealing the free-energy barrier among stable states was developed by combining the multicanonical ensemble with the weighted histogram analysis method (WHAM). The method, called multicanonical WHAM, was applied to the cis/trans-imide isomerization of a blocked peptide dimer, –Ala–Pro–. Many conformations around the transition states with high potential energies were sampled. From the reweighted canonical ensemble at 300 K, the landscape of the potential of mean force covering the transition states and the two stable cis- and trans-isomer states was observed. The structural transition paths between the cis- and trans-isomer states are discussed.