title: Ligand and Structure-Based Approaches for the Identification of Peptide Deformylase Inhibitors as Antibacterial Drugs.
abstract: Peptide deformylase (PDF) is a metalloprotease catalyzing the removal of a formyl group from newly synthesized proteins, which makes it an important antibacterial drug target. Given the importance of PDF inhibitors like actinonin in antibacterial drug discovery, several reported potent PDF inhibitors were used to develop pharmacophore models using the Galahad module of Sybyl 7.1 software. Generated pharmacophore models were composed of two donor atom centers, four acceptor atom centers and two hydrophobic groups. Model-1 was screened against the Zinc database and several compounds were retrieved as hits. Compounds with Qfit values of more than 60 were employed to perform a molecular docking study with the receptor Escherichia coli PDF, then compounds with docking score values of more than 6 were used to predict the in silico pharmacokinetic and toxicity risk via OSIRIS property explorer. Two known PDF inhibitors were also used to perform a molecular docking study with E. coli PDF as reference molecules. The results of the molecular docking study were validated by reproducing the crystal structure of actinonin. Molecular docking and in silico pharmacokinetic and toxicity prediction studies suggested that ZINC08740166 has a relatively high docking score of 7.44 and a drug score of 0.78.
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China. gaojian@xzhmu.edu.cn.|Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China. gaojian@xzhmu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China. 18852143485@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China. 18151865223@163.com.
authors.forename: Yasheng
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China. neoevens@hotmail.com.
authors.forename: Shengzhi
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China. lswangtao@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China. zhamgling1999@163.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry* / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D006877:Hydroxamic Acids / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011487:Protein Conformation
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D008024:Ligands; D000581:Amidohydrolases; C084507:peptide deformylase; C010531:actinonin
keywords: antibacterial drug; high-throughput virtual screening; molecular docking; peptide deformylase; pharmacophore model