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Research and Reviews : Journal of Computational Biology Original Research

Computational Investigation of Phytochemicals Targeting AKT1 for Major Depressive Disorder: A Molecular Docking and ADMET Study

  1. Chakresh Kumar Jain Department of Biotechnology, Jaypee Institute of Information Technology, Noida
  2. Abhimanyu Chauhan Department of Biotechnology, Jaypee Institute of Information Technology, Noida

Abstract

Major depressive disorder (MDD) is a prevalent neuropsychiatric condition affecting approximately 280 million individuals worldwide, with women exhibiting a 50% higher likelihood of diagnosis than men. Despite significant advancements in treatment, MDD remains a chronic and relapsing disorder, necessitating the exploration of novel therapeutic interventions. This study focuses on the AKT1 gene, a key player in neuropsychiatric disorders, and investigates its interactions with natural phytochemicals as potential alternatives to conventional antidepressants. Molecular docking analysis was conducted using the AKT1 protein structure (PDB ID: 3O96) to evaluate the binding affinities of FDA-approved antidepressants and selected phytochemicals derived from Ayurvedic medicinal plants. Active site prediction using CASTpFold identified a binding pocket with a surface area of 1665.060 Ų and a volume of 1365.991 ų. Docking studies revealed that Cannflavin A and Betulinic Acid exhibited superior binding affinities (-10.6 and -10.3 kcal/mol, respectively) compared to Paroxetine (-10.2 kcal/mol) and Sertraline (-9.7 kcal/mol). Interaction analysis highlighted stronger hydrogen bonding, hydrophobic interactions, and van der Waals forces in Cannflavin A compared to Paroxetine, suggesting enhanced binding stability. Furthermore, ADMET analysis confirmed favorable pharmacokinetic properties for Cannflavin A, reinforcing its potential as a natural therapeutic agent for MDD. These findings underscore the promise of phytochemicals in modulating AKT1 activity and provide a foundation for future preclinical and clinical investigations into their antidepressant potential

Keywords

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