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Updated: Apr 21, 2026
Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Molecular dynamics approach to probe PKCβII-ligand interactions and influence of crystal water molecules on these
Baljinder K Grewal1, Jyotsna Bhat, Masilamani Elizabeth Sobhia
1National Institute of Pharmaceutical Education and Research (NIPER), Department of Pharmacoinformatics , Sector 67, S.A.S. Nagar, Punjab 160062 , India +91 172 2211343 ; +91 172 2214692 ; mesophia@niper.ac.in.
Objective:
PKCβII is a potential target for therapeutic intervention against pandemic diabetic complications. Present study probes the molecular interactions of PKCβII with its clinically important ligands, viz. ruboxistaurin, enzastaurin and co-crystallized ligand, 2-methyl-1H-indol-3-yl-BIM-1.
Research Design And Methods:
The essentials of PKCβII-ligand interaction, crystal water-induced alterations in these interactions and key interacting flexible residues are analyzed. Computational methodologies, viz. molecular docking and molecular simulation coupled with molecular mechanics-Poisson-Boltzmann surface area and generalized born surface area (MM-PB[GB]SA) are employed.
Results:
The structural changes in the presence and absence of crystal water molecules in PKCβII ATP binding site residues, and its interaction with bound ligand, are identified. Difference in interaction of selective and nonselective ligand with ATP binding site residues of PKCβII is reported.
Conclusions:
The study showed that the nonbonding interactions contribute significantly in PKCβII-ligand binding and presence of crystal water molecules affects the interactions. The findings of present work may integrate the new aspects in the drug design process of PKCβII inhibitors.
