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

Abstract

2-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.

• Authors: Naruedon Phusi, Riku Sato, Takuya Ezawa, Shogo Tomioka, Chayanin Hanwarinroj, Bandit Khamsri, Pharit Kamsri, Auradee Punkvang, Pornpan Pungpo, Noriyuki Kurita
• Journal: Journal of molecular graphics & modelling (J Mol Graph Model) Vol. 88 Pg. 299-308 (05 2019) ISSN: 1873-4243 [Electronic] United States
• PMID: 30826710 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Acyl Carrier Protein
• Amino Acids
• Ligands
• Water
• Oxidoreductases

Topics

• Acyl Carrier Protein (chemistry, metabolism)
• Amino Acids (chemistry)
• Ligands
• Molecular Docking Simulation
• Molecular Dynamics Simulation
• Molecular Structure
• Oxidoreductases (chemistry, metabolism)
• Protein Conformation
• Structure-Activity Relationship
• Water (chemistry)