Identification of Potent Bioactive Molecules Against NMDA Receptor and Tau Protein by Molecular Docking Approach

Introduction: N-methyl-d-aspartate receptor (NMDAR) and tau protein play an important role in neuronal death due to cerebral ischemia or ischemic stroke. Unfortunately, no drug has been discovered except tissue plasminogen activator (tPA) to fight against ischemic stroke. Virtual high throughput screening to find out possibilities of bioactive molecules to target NMDAR and tau protein to treat ischemic stroke may be an option for drug discovery. Objective: The current study aimed to assess the molecular interaction of some bioactive molecules with NMDAR and tau protein in silico to incriminate ischemic stroke. Methods: A computational method based on ligand-protein interaction technique has been used in the present study to identify the therapeutic potential of some bioactive molecules for the possible treatment of ischemic stroke. For this purpose, 50 bioactive molecules were screened and docking analysis was performed for two target proteins, NMDAR and tau protein. In this study, for each protein target, the best poses were identified based on binding energy and inhibition constant. Different pharmacological properties of selected bioactive molecules were also analyzed to determine their absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties in silico. All were found in the acceptable range and followed Lipinski’s rule. Results: In the present study of the 50 screened bioactive molecules, top 10 molecules have been identified, of which best two bioactive molecules such as gossypin, viniferin have been predicted to be potential neuroprotective agents against cerebral ischemia induced alteration of NMDAR and tau protein functional integrities. Conclusion: Gossypin’ was the best bioactive compound interacting with NMDAR and tau protein.