Structural modeling of viral protein 2 of bluetongue virus And in silico mechanistic elucidation for memberane Penetration and its implications for vaccine development

Abstract

Bluetongue disease currently noticeable to the World Organization for Animal newlineHealth (OIE); causes enormous economic losses due to rapid deteriorate trade newlineassociated with bluetongue outbreaks and high mortality and morbidity. The newlinecapsid coat protein of Bluetongue Virus (BTV), Viral Protein 2 (VP2) is responsible newlinefor BTV transmission by the Culicoides vector to vertebrate hosts during blood newlinefeeding. Seven polypeptides have been found to be present in the capsid of the newlineBTV, four of which are major and three are minor components. Besides, VP2 is newlineresponsible for BTV entry into permissive cells and hence plays a major role in newlinedisease progression. However, its mechanism of action is not known till date. The newlinepresent investigation aimed to predict the 3D structure of VP2 of BTV followed by newlineStructure validation, Molecular Dynamics Simulation and active site prediction. newlineThe In silico approach provides a platform for determining the structure of the VP2 newlineprotein. The 3D structure of VP2 protein was built using a Python-based newlineComputational algorithm. The templates were identified using Smith Waterman s newlinev newlineLocal alignment. The VP2 protein structure was validated using PROCHECK and newlinepresented using Ramachandran plots. Molecular Dynamics Simulation studies newlinewere performed using an academic software Desmond, Schrodinger dynamics for newlinedetermining the stability of model protein. The Ligand-Binding site was predicted newlineby a homology searching by structure comparison and protein-protein in networks newlineanalysis, to reveals their stability and inhibition mechanism followed by active site newlineidentification. The secondary structure of the model concluded that the model newlinecontains 220 Alpha Helix atoms, 40310Helix, 151 Beta sheets, 134 coils and 424 newlineturns. The 3D structure of VP 2 of BTV was found to have 15774 total atoms in the newlinestructure.961 amino acids were found the final model. A novel application of MD newlinefollowing with the dynamical cross-correlation matrix (DCCM) analysis tool was newlineused to identify putative protein domains to confirm the stability o