title: An exhaustive yet simple virtual screening campaign against Sortase A from multiple drug resistant Staphylococcus aureus.
abstract: Methicillin resistant Staphylococcus aureus (MRSA) is one of the challenging bacterial pathogen due to its acquired resistance to the β lactam antibiotics. The Sortase A is an enzyme of Gram-positive bacteria including S. aureus to anchor surface proteins to the cell wall. Sortase A is well studied enzyme and considered as the drug target against MRSA. Sortase A plays active role in anchoring the virulence proteins on the cell wall of the Gram-positive bacteria. The inhibition of Sortase A activity results in the separation of S. aureus from the host cells and ultimately alleviation of the infection. Here, we adapted a structure-based virtual screening protocol which helped in identification of novel potential inhibitors of Sortase A. The protocol involved the docking of a chemical library of druglike compounds with the Sortase A binding site represented by multiple crystal structures. The compounds were ranked by multiple scoring functions and shortlisted for future experimental screening. The method resulted in shortlisting of three compounds as potential novel inhibitors of Sortase A out of a large chemical library. The high rankings of shortlisted compounds estimated by multiple scoring functions showed their binding potential with Sortase A. The results are proved to be a simple yet efficient choice of structure-based virtual screening. The identified compounds are druglike and show high rankings among all set protocols of the virtual screening. We hope that the study would eventually help to expedite the discovery of novel drug candidates against MRSA.
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan, mriazuddin@iccs.edu.
authors.forename: Reaz
authors.initials: R
authors.lastname: Uddin
authors.forename: Kiran
authors.initials: K
authors.lastname: Saeed
mesh_terms: D000595:Amino Acid Sequence; D019881:Aminoacyltransferases / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000201:enzymology*; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment; D054852:Small Molecule Libraries / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D054852:Small Molecule Libraries; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases