Identification of possible drug target for NMDA receptor and tau protein by insilico method

Abstract

Background: Stroke is the most prevalent form of neurological disorder one of the leading causes of death worldwide. The molecular mechanism that underlies is not well understood. NMDA (N-methyl-d-aspartate) receptor (NMDAR) and tau protein are involved in the progression of stroke. Thrombolytic drug, recombinant tissue plasminogen activator is commonly used for the treatment of stroke but still potent pharmacological treatments are not developed. Insilico drug discovery process provides a new approach for ischemic stroke. Objective: The objective of the current study to screening potent bioactive molecules and to understand their interaction with on the molecular interaction with NMDAR and tau protein by using molecular docking approach Result: A protein-ligand docking method was employed for the present study. Ligand library is created by screening the phytochemical database. Approximately 50 bioactive molecules were screened from and docking analysis was performed on two target proteins (NMDAR and tau protein). Through docking analysis best poses were identified for each protein. The analysis is performed on the basis of binding energy and inhibition constant. Different pharmacological properties of selected drug molecules were also analyzed to determine the in silico ADME properties of these drugs and all were found in the acceptable range and follows Lipinski's rule. Conclusion: The present study has identified the potential bioactive molecules such as gossypin, viniferinetc may act as possible neuroprotective agents against any cerebral ischemia induces alteration of NMDAR and tau protein functional integrities. Further among the selected 10 molecules 'gossypin' was found to be the best bioactive compound interacting with NMDAR and tau protein.