Computational Insights into the Aggregation Behavior of Dengue Virus NS1 Oligomerization Domain, 2k and Capsid Anchor Peptides

ABSTRACT Dengue virus, an arbovirus and member of Genus Flavivirus leads to thousands of deaths round the globe. The virus encodes for a polyprotein which gets 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 aggregation propensity which has been previously associated with many co‐morbid diseases. Here, we have tried to shed light into this aggregation perspective of these three peptides making use of multiple long length all atom MD simulations to study the aggregation behavior of the peptides in atomistic detail. The aggregation kinetics of peptide aggregation has been studied based on the aggregate size method and the solvent accessible surface area method giving a direct estimate of the the aggregation seed development process. The timescale of aggregation has been studied making use of a Hidden Markov Model based on PCA method. The importance of the different peptide residues has been elucidated using mutational landscape profiling. This study may shed light into the aggregation propensity of these three peptides and help to explain viral pathogenesis pathway in greater detail in foreseeable future.