Structure Insights and Fibrinogen Peptides Molecular Recognition by Bothrombin, A Snake Venom Serine Protease from Bothropus jararaca

Abstract

Bothrombin is a snake venom serine protease from Bothropus jararaca, which aggregates platelets in the presence of fibrinogen. In this context, the 3D model of Bothrombin was design for molecular modeling studies by modeller9v5 using as template the protein C Activator (PDB ID 2AIP). Energy minimized Bothrombin model was validated by methods such as PROCHECK, PROSA, ERRAT, WHAT-IF and VERITY 3D. After confirming all suggested evidences, such as geometric quality of the backbone conformation, residue interaction, energy profile etc., the interaction study based on docking was further calculated with ClusPro server. This protocol was designed in order to assess the dependence of bothrombin model from its template and how it compares to thrombin. Crystal structure of fibrinopeptides of PDB ID: 1DM4 and 1YCP were selected for docking studies. These fibrinopeptide also docked with thrombin and protein C Activator. All docked complexes were then further analysed by means of interaction energy between subunits and their corresponding binding energy estimates. The present study gain insight into protein structure-function relationships among serine proteinases, and its importance in biomedical applications.