Title: In silico virtual screening of PubChem compounds against phosphotransacetylase, a putative drug target for Staphylococcus aureus
Authors: P. Bharath Siva Varma; Yesu Babu Adimulam; K. Subrahmanyam
Addresses: Department of Computer Science & Engineering, SRKR Engineering College, Bhimavaram, 534201, India ' Department of Computer Science & Engineering, Sir C.R. Reddy College of Engineering, Eluru, Andhra Pradesh, 534007, India ' Department of Computer Science and Engineering, K L University, Vijayawada, 522502, India
Abstract: Reports on in silico based detection of putative drug candidates in the metabolic pathway of S. aureus resulted in non-homologous target genes with no close human analogue. Therefore, Phosphotransacetylase (PTA) was evaluated as promising drug target against S. aureus. An in silico virtual screening of PubChem compounds with enhanced binding energies when compared with reference ligand, acetyl phosphate (DB02897) was presented. 4E4R was selected as protein target and screening of 238 PubChem compounds with phosphotransacetylase was performed. Docking analysis resulted in binding energies ranging from −58.13 kcal/mol to −191.515 kcal/mol. Based on the interaction energies of ligands, top five compounds are reported and it was observed that compound 1 (ID: 10096390) displayed better inhibitory activities than the remaining. Interestingly, of all five compounds, except compound 1, all other molecules violated Lipinski rule and therefore, we report compound 1, with dock score −191.515 kcal/mol as the best inhibitor against phosphotransacetylase.
Keywords: phosphotransacetylase; PTA; Staphylococcus aureus; docking analysis; MRSA; in silico virtual screening; PubChem compounds; drug targets; metabolic pathways; S. aureus; binding energies; ligands; inhibitors.
International Journal of Computational Biology and Drug Design, 2017 Vol.10 No.1, pp.39 - 48
Received: 01 Feb 2016
Accepted: 12 Apr 2016
Published online: 07 Mar 2017 *