Ashek, A Cho, SJ 2024-01-21T03:33:01Z 2024-01-21T03:33:01Z 2022-01-10 2006-03-01 0968-0896 https://pubs.kist.re.kr/handle/201004/135662 The enzyme FabH catalyzes the initial step of fatty acid biosynthesis via a type II fatty acid synthase. The pivotal role of this essential enzyme combined with its unique structural features and ubiquitous occurrence in bacteria has made it an attractive new target for the development of antibacterial and antiparasitic compounds. Three-dimensional quantitative structure-activity relationship (3D QSAR) studies such as comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) and docking simulations were conducted on a series of potent benzoylaminobenzoic acids. Docking studies were employed to position the inhibitors into the FabH active site to determine the probable binding conformation. A reasonable correlation between the predicated binding free energy and the inhibitory activity was found. CoMFA and CoMSIA were performed based on the docking conformations, giving q(2) of 0.637 and 0.697 for CoMFA and CoMSIA models, respectively. The predictive ability of the models was validated using a set of compounds that were not included in the training set and progressive scrambling test. Mapping the 3D QSAR models to the active site of FabH related that some important amino acid residues are responsible for protein-inhibitor interaction. These results should be applicable to the prediction of the activities of new FabH inhibitors, as well as providing structural understanding. (c) 2005 Elsevier Ltd. All rights reserved. English PERGAMON-ELSEVIER SCIENCE LTD INCREMENTAL CONSTRUCTION ALGORITHM FATTY-ACID SYNTHASE MYCOBACTERIUM-TUBERCULOSIS FIELD CLONING DESIGN TARGET A combined approach of docking and 3D QSAR study of beta-ketoacyl-acyl carrier protein synthase III (FabH) inhibitors Article 10.1016/j.bmc.2005.10.001 1 BIOORGANIC & MEDICINAL CHEMISTRY, v.14, no.5, pp.1474 - 1482 BIOORGANIC & MEDICINAL CHEMISTRY 14 5 1474 1482 scie scopus 000235244400019 2-s2.0-31044451279 Biochemistry & Molecular Biology Chemistry, Medicinal Chemistry, Organic Biochemistry & Molecular Biology Pharmacology & Pharmacy Chemistry Article INCREMENTAL CONSTRUCTION ALGORITHM FATTY-ACID SYNTHASE MYCOBACTERIUM-TUBERCULOSIS FIELD CLONING DESIGN TARGET docking CoMFA CoMSIA FabH antibiotic