All-Atom Molecular Dynamics Simulation Methods for the Aggregation of Protein and Peptides: Replica Exchange/Permutation and Nonequilibrium Simulations

Protein aggregates are associated with more than 40 serious human diseases. To understand the formation mechanism of protein aggregates at atomic level, all-atom molecular dynamics (MD) simulation is a powerful computational tool. In this chapter, we review the all-atom MD simulation methods that are useful for study on the protein aggregation. We first explain conventional MD simulation methods in physical statistical ensembles, such as the canonical and isothermal-isobaric ensembles. We then describe the generalized-ensemble algorithms such as replica-exchange and replica-permutation MD methods. These methods can overcome a difficulty, in which simulations tend to get trapped in local-minimum free-energy states. Finally we explain the nonequilibrium MD method. Some simulation results based on these methods are also presented.