Homology Modeling and Molecular Docking Studies of Bacillomycin and Iturin Synthetases with Novel Ligands for the Production of Therapeutic Lipopeptides

摘要

Background: Lipopeptide synthetases play an important role in the productionof lipopeptides. Lipopeptides are molecules made up of peptides and fatty acid moietiesand have shown to have a broad range of antimicrobial activity. As infectious diseaseshave caused severe health problems mainly resulting from the development of antibioticresistant strains of disease causing microorganisms there is a need of alternatives to antibiotics.The lipopeptide synthetase of the corresponding lipopeptides can be used as templateto design these as drugs using computational techniques.Objective: The objective of this study was homology modeling and molecular dockingof two lipopeptide synthetases, bacillomycin D synthetase and iturin A synthetase,with their ligands as a means of drug design.Method: Schr?dinger software was used for homology modeling and molecular docking.Results: After the identification of ligands, molecular docking of these ligands withthe lipopeptide (bacillomycin and iturin) synthetases was performed. The dockingwas tested on the parameters of docking score and glide energy. 5 out of 21 ligandswere found to dock with bacillomycin D synthetase whereas 8 out of 20 ligandsdocked with the iturin A synthetase.Conclusion: The knowledge of the docking sites and docking characteristics of thelipopeptide synthetases mentioned in the paper with the ligands can provide advantages ofhigh speed and reliability, reduced costs on chemicals and experiments and the ethical issuesconcerned with the use of animal models for screening of drug toxicity.