In silico identification of novel ligand molecules for rabies nucleoprotein using structure-based method.

Abstract:

Background: Rabies is a life-threatening condition which much privileged in Asia and Africa causes high mortality annually. It has to be treated before showing of any clinical signs. Presently vaccination is the lone accessible medication. Several research are taking place around worldwide for production of epitope based and DNA vaccines. Rabies Nucleoprotein plays a decisive role in transcription and replication process in rabies virus. In this study 2 ligand molecules were identified to prevent transcription and replication of rabies virus. Methods: Three dimensional structure of nucleoprotein model was modeled using Phyre2 server. The protein structure validation was carried out in Ramachandran plot by RAMPAGE. Energy minimization was performed for molecular dynamics study which was proceeded using Gromacs 5.1. Structure based pharmacophore method was employed to identify the ligand molecules against nucleoprotein by Ligand Scout. Molecular docking studies was executed in Auto Dock tools. Loop docking scheme has done for validation of binding energy. Results: 12 molecules were presenting reasonable binding energy interaction with nucleoprotein. Two ligand compounds ZINC10530604 and ZINC10530605 were exhibit virtuous binding energy -8.0 and -7.3 respectively. Conclusion: The identified ligands can be potential drug compound against rabies nucleoprotein by either preventing or inhibiting of transcriptional and translational activity.

Key words: Nucleoprotein, Homology modeling, Energy minimization and Simulation, Structure-based pharmacophore, Molecular docking.