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Updated: Apr 2, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Multiple ligand simultaneous docking (MLSD): A novel approach to study the effect of inhibitors on substrate binding
S Raghavendra1, S J Aditya Rao2, Vadlapudi Kumar3
1College of Horticulture, University of Horticulture Sciences, Bagalkot 587102, Karnataka, India.
Abstract:
Multiple ligand simultaneous docking, a computational approach is used to study the concurrent interactions between substrate and the macromolecule binding together in the presence of an inhibitor. The present investigation deals with the study of the effect of different inhibitors on binding of substrate to the protein Polyphenoloxidase (PPO). The protein was isolated from Mucuna pruriens and confirmed as tyrosinases involved in L-DOPA production. The activity was measured using different inhibitors at different concentrations taking catechol as substrate. A high-throughput binding study was conducted to compare the binding orientations of individual ligands and multiple ligands employing Autodock 4.2. The results of single substrate docking showed a better binding of urea with the binding energy of -3.48 kJ mol(-1) and inter molecular energy of -3.48 kJ mol(-1) while the results of MLSD revealed that ascorbic acid combined with the substrate showed better inhibition with a decreased binding energy of -2.37 kJ mol(-1).
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