Specific interactions between 2-trans enoyl-acyl carrier protein reductase and its ligand: Protein-ligand docking and ab initio fragment molecular orbital calculations

Publication date: Available online 25 February 2019Source: Journal of Molecular Graphics and ModellingAuthor(s): Naruedon Phusi, Riku Sato, Takuya Ezawa, Shogo Tomioka, Chayanin Hanwarinroj, Bandit Khamsri, Pharit Kamsri, Auradee Punkvang, Pornpan Pungpo, Noriyuki KuritaAbstract2-trans enoyl-acyl carrier protein reductase (InhA) has been identified as a promising target for the development of novel chemotherapy for tuberculosis. In the present study, a series of heteroaryl benzamide derivatives were selected as potent inhibitors against InhA, and their binding properties with InhA were investigated at atomic and electronic levels by ab initio molecular simulations based on protein-ligand docking, classical molecular mechanics optimizations and ab initio fragment molecular orbital (FMO) calculations. The results evaluated by FMO highlight some key interactions between InhA and the derivatives, indicating that the most potent derivative has strong hydrogen bonds with the Met98 side chain of InhA and strong electrostatic interactions with the nicotinamide adenine dinucleotide cofactor. These findings provide informative structural concepts for designing novel heteroaryl benzamide derivatives with higher binding affinity to InhA.Graphical abstractInteracting structures between the InhA residues and the derivative A4/B4. Red, blue and black lines indicate hydrogen bonding, electrostatic and π-π interactions, respectively.

Source: Journal of Molecular Graphics and Modelling - February 25, 2019 Category: Molecular Biology Source Type: research