Explicit-Solvent All-Atom Molecular Dynamics of Peptide Aggregation

Recent advances in computational technology have allowed us to sim2 ulate biomolecular processes on timescales that begin to reach the rates of peptide 3 aggregation phenomena.Molecular dynamics simulations have evolved into amature 4 technique to the extent that they can be employed as a highly productive tool to gain 5 meaningful insights into the structure, dynamics and molecular mechanisms of pro6 tein aggregation. In this chapter, we describe the basics of explicit solvent all-atom 7 molecular dynamics simulations and its applications for studying early stages of 8 aggregation processes of two short pentapeptides: KLVFF and FVFLM, related to 9 Alzheimer’s disease and preeclampsia, respectively. We focus on certain important 10 problems in the field of protein aggregation that explicit solvent all-atom molecular 11 dynamics simulation studies could resolve. This includes how fibril formation rates 12 depend on a number of factors such as the presence of short peptides and popula13 tion of fibril-prone conformations. Specific applications of atomistic simulations in 14 explicit solvent to address these two issues are discussed.