Lipopeptides as Therapeutics: Molecular Docking and Drug Design

Abstract

The rise of antibiotic-resistant pathogens has led to an urgent requirement of potent and safe antimicrobial compounds. Lipopeptides produced as secondary metabolites by some organisms have shown a broad range of anti-pathogenic activities, while some have anti-cancerous properties as well. Among all the lipopeptides, daptomycin has gained popularity as biopharmaceutical. In order for the lipopeptides to be used as drugs, in silico drug designing of these compounds should be performed which enables the identification of the presence of binding sites in lipopeptides for their corresponding ligands. In this study, molecular docking of daptomycin with its ligands was performed as a method of designing novel drug. After the identification of ligands, namely, D-alanine, decanoic acid, D-asparagine, D-serine, (2S)-2-amino-4-(2-aminophenyl)-4-oxobutanoic acid, and (2S,3R)-2-azanyl-3-methyl-pentanedioic acid, using RSCB, Schrödinger software was used to dock daptomycin with their corresponding ligands. After the identification of ligands, they were made to dock with daptomycin. The parameters for docking were docking score and glide energy. Out of the six identified ligands of daptomycin, only three were found to dock with it with docking scores of −3.229 (for D-alanine), − (for D-asparagine), and −4.216 (for D-serine). Their respective glide energies were −13.678 kcal/mol (D-alanine), −22.56 kcal/mol (D-asparagine), and −12.042 kcal/mol (D-serine).