In-silico comparative modeling and interaction studies of PRSV proteins - Accelerated towards dissection of structure based evolutionary divergence and functional interaction of virus within the host

Function based structure analysis of viral proteins reinforce their distinctive and unanticipated role within the host. The interaction dynamics of virus protein and host which is prerequisite for complete infectivity as well as systemic spread of invading virus demands to explore viral proteins in framework of their interacting partners. Papaya ringspot virus strain from Pakistan (PRSV-PK) spreading as atypical variant and causes drastic reduction in papaya production. The in-depth knowledge of the virus variant and effective management is obligatory. The desired objective is achievable once the evolutionary dynamics, molecular characterization and physicochemical structural properties conceived from the 3D protein structures are comprehended. Although the diversity studies on PRSV-PK strain been established but still there is a niche regarding structural based evolutionary dynamics of virus proteins and their probable interaction mode inside the host. The present investigations provided insights into the in-silico analysis of the functionally significant genes Coat protein (CP), Helper component proteinase (HC-Pro) and Nuclear Inclusion b protein (NIb) of PRSV-PK. The protein structure has been modeled using Phyre2, Swiss-Model and i-TASSER. Phyre2 built model showed 100% confidence for 67%, 63% and 20% sequence identity residues for PRSV CP, HC-Pro and NIb proteins respectively. The Swiss model showed identity values of 63.40%, 62.42% and 16.49% for CP, HC-Pro and NIb protein. whereas, i-TASSER server exhibited identity values of 67%, 63% and 19% for CP, HC-Pro and NIb proteins respectively. These structures provided a base line for functional analysis of experimentally derived crystal structures. The predicted models were validated using protein structure checking tools PROCHECK. Further the PRSV-PK-CP structures were compared with the PRSV-CP structures of representative isolates from different geographical regions. Nevertheless, the comparative modeling provides the insight into the evolutionary characteristics and proposed genetic diversity of PRSV based on protein structures. In addition, the conserved functional motifs have been mapped on aligned protein sequences of CP, HC-Pro and NIb, and their critical function within the host has been highlighted. Eventually, the interaction of papaya protein with the invading PRSV-CP has been predicted through in-silico protein-protein docking to elucidate their possible role in virus inhibition. The established structural-functional relation provided a basis to propose probable host-virus interactions in terms of virus infectivity, resultant host adaptability, and host defense response activation to counteract the virus invasion.