V3I1P79

Computational Investigation of Structural Stability and Binding Affinity of Ligand 1D45 toward HIV-1 Protease

Dr. Devidutta Maurya^1*

Abstract

The emergence of drug resistance in Human Immunodeficiency Virus type-1 (HIV-1) necessitates continuous exploration of potent protease inhibitors with improved structural stability and binding efficiency. In this study, a computational investigation was carried out to elucidate the structural stability and binding affinity of ligand 1D45 toward HIV-1 protease using an integrated in silico approach. The three-dimensional structure of the protein–ligand complex was obtained from the Protein Data Bank and prepared for computational analysis. Molecular docking simulations were performed to evaluate the binding orientation, interaction pattern, and binding energy of ligand 1D45 within the active site of HIV-1 protease. The docking results revealed a favorable binding affinity, with ligand 1D45 occupying the catalytic pocket and forming key hydrogen bond interactions with the conserved active-site residues, particularly the catalytic aspartates, along with stabilizing hydrophobic contacts. Structural stability of the complex was assessed through conformational analysis, indicating minimal steric clashes and a well-accommodated ligand geometry within the binding cavity. The interaction profile suggests that the hydroxyethylamine core of ligand 1D45 plays a crucial role in mimicking the transition state of peptide cleavage, thereby enhancing inhibitory potential. Overall, the computational findings provide molecular-level insights into the binding mechanism and stability of the HIV-1 protease–1D45 complex, highlighting ligand 1D45 as a promising scaffold for the rational design and optimization of next-generation HIV-1 protease inhibitors.

Keywords:

HIV-1 protease; protease inhibitors; molecular docking; binding affinity; in silico analysis