Identification of novel scaffolds to inhibit Mycobacterium tuberculosis PimA protein—A computational approach

Abstract Phosphatidyl‐myo‐inositol mannosyltransferase (Pim) is a subset of the Glycosyl transferase type family that has been synthesized from 1D‐myo‐inositol and GDP‐α‐ d ‐mannose reaction in the presence of PimA protein as a catalyst, which PimA protein is identified as a high‐confidence therapeutic target. In‐silico technique such as homology modeling is the most efficient approach for discovering a new framework to study the modulations of protein function. Using In‐silico approaches, therapeutic compounds with high affinity, specificity, activity, low harmfulness, and no side effects can be found. Applying the Modeller software and molecular dynamics simulations, a stable three‐dimensional (3D) model of the PimA protein is produced. The modeled PimA protein consists of 20 helices and 27 twists in its 3D structure. Lead compounds that inhibit the PimA protein are found by applying the Schrodinger suite and the PyRx virtual screening tools. The amino acid residues PRO14 and ASP253 are identified as active residues involved in binding with the ligands. High‐potential lead compounds are discovered as ligand scaffolds against PimA protein with satisfactory ADME capabilities.