Discovering Innovative Treatments: Molecular Docking in the Fight Against Drug Resistance with Tetrahydroquinoline Derivatives and hGSTP1-1

Abstract

The molecular docking methodology investigates the behavior of small molecules within the binding sites of target proteins. As an increasing number of protein structures are elucidated through experimental techniques such as X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, molecular docking has gained prominence as an essential tool in drug discovery. It also facilitates docking against homology-modeled targets for proteins with unknown structures. Through various docking strategies, it is possible to calculate the druggability of compounds along with their specificity to particular targets, thereby aiding in lead optimization processes. Molecular docking programs employ search algorithms that recursively evaluate ligand conformations until convergence is achieved at the minimum energy state. Ultimately, an affinity scoring function, denoted as ΔG [U total in kcal/mol], ranks candidate poses based on the summation of electrostatic and van der Waals energies. The driving forces behind these specific interactions in biological systems center on the complementarities between the geometries and electrostatics of the binding site surfaces and the ligand or substrate.