Open AccessMolecular docking of modified ipalbidine ligands into human cyclooxygenase-2 protein crystal structures
Author(s) -
Bernhard Egwolf,
Jeidrick Maxy A. Gumawid
Publication year - 2020
Publication title -
journal of physics. conference series
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.21
H-Index - 85
eISSN - 1742-6596
pISSN - 1742-6588
DOI - 10.1088/1742-6596/1529/3/032060
Subject(s) - docking (animal) , chemistry , hydrogen bond , autodock , binding site , stereochemistry , ligand (biochemistry) , active site , chirality (physics) , drug , selectivity , affinities , plasma protein binding , pharmacology , biochemistry , enzyme , medicine , receptor , catalysis , molecule , organic chemistry , gene , nursing , chiral symmetry breaking , physics , quantum mechanics , nambu–jona lasinio model , in silico , quark
With many negative side-effects of nonsteroidal anti-inflammatory drugs such as gastrointestinal problems and the withdrawal of most selective COX-2 inhibitors from the market due to its increased risk of heart disease, there is a demand for an alternative analgesic (pain reliever) with less adverse side-effects. Nowadays, molecular docking is a major computational tool for drug development and drug design. This study focuses on the modification of potential analgesic ipalbidine in order to optimize its binding affinity to seven human COX-2 structures using Autodock Vina as a docking tool. Two different modified ligands were successfully enclosed in the COX-2 protein structure and were able to bind to the binding site. Based on the obtained binding affinities, it was found that by increasing the amount of hydrogen atoms on the ligand by converting the carbon double bond into a single bond, the binding affinity was reduced due to the hydrophobicity of the binding site liners. The second change was ipalbidine with inverted chirality. Inverted chirality showed higher binding affinities across the board, implying improved efficacy and bond strength. However, a change in the chirality of a drug may alter the selectivity or effect of the drug as a whole, and therefore clinical trials may be required to identify possible side-effects that may arise.