Computational Cross-Aggregation Study of Dengue Virus NS1, Capsid Anchor and 2k Peptides With Human Amylin, Aβ42 and α-Synuclein Peptides

Abstract

Dengue virus, an arbovirus, is the causal factor of thousands of deaths around the globe, although the long-term consequences of the same have not been elucidated in great detail. The virus encodes for a polyprotein, which is later cleaved to form multiple proteins, of which NS1 protein oligomerization domain, 2k, and capsid anchor are three aggregation-prone peptides, as have been previously seen. A relatively under-studied angle of these peptides is the role of these peptides in cross-aggregation with certain human aggregation-prone proteins. Here, we have tried to shed light on this cross-aggregation perspective of these three peptides in combination with human amylin, α-synuclein, and Aβ42 peptides, making use of extensive all-atom MD simulations to study the cross-aggregation behavior of the peptides in atomistic detail. The intricacies of peptide aggregation have been studied based on the aggregate size calculation and the solvent accessible surface area method, giving a direct estimate of the aggregation seed development process. The importance of the different peptide residues in both self and cross-aggregation has been elucidated. This study may shed light on the cross-aggregation potential of these three peptides and help to explain the viral pathogenesis pathway in greater detail.