New Molecular Simulation Methods to Study Rare Events―Simulation Studies for Understanding Amyloidogenesis―

Abstract

It is difficult to obtain sufficient sampling in the conformational space for biomolecules. This is because biomolecular systems usually have many free-energy local-minimum states, and in conventional canonical-ensemble simulations, the system gets trapped in such local-minimum states. To solve this problem, we recently proposed the replica-permutation method and the Hamiltonian replica-permutation method. Moreover, we applied the Hamiltonian replica-permutation method to fragments of amyloid-β peptides to investigate their dimerization process. The amyloid-β peptide tends to form amyloid fibrils, which are associated with the Alzheimer's disease. The dimerization process corresponds to the early stage of the amyloid fibril formation process. It is necessary to clarify the dimerization process in order to find a remedy for Alzheimer's disease.