Aggregation kinetics of short peptides: All-atom and coarse-grained molecular dynamics study.

Peptides can aggregate into ordered structures with different morphologies. The aggregation mechanism and evolving structures are the subject of intense research. In this paper we have used molecular dynamics to examine the sequence-dependence of aggregation kinetics for three short peptides: octaalanine (Ala8), octaasparagine (Asn8), and the heptapeptide GNNQQNY (abbreviated as GNN). First, we compared the aggregation of 20 randomly distributed peptides using the coarse-grained MARTINI force field and the atomistic OPLS-AA force field. We found that the MARTINI and OPLS-AA aggregation kinetics are similar for Ala8, Asn8, and GNN. Second, we used the MARTINI force field to study the early stages of aggregation kinetics for a larger system with 72 peptides. In the initial stage of aggregation small clusters grow by monomer addition. In the second stage, when the free monomers are depleted, the dominant cluster growth path is cluster-cluster coalescence. We quantified the aggregation kinetics in terms of rate equations. Our study shows that the initial aggregation kinetics are similar for Ala8, Asn8, and GNN but the molecular details can be different, especially for MARTINI Ala8. We hypothesize that peptide aggregation proceed in two steps. In the first step amorphous aggregates are formed, and then, in the second step, they reorganize into ordered structures. We conclude that sequence-specific differences show up in the second step of aggregation.