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.

An eco‐efficient new path of mortar pestle grinding approach for the construction of methanol and ethylthio substituted pyridines with in silico studies

“…The major elements of Mycobacterium TB' cell wall include mycolic acids [49]. Numerous studies suggest that the pathogenesis and durability of mycolic acids depend on the functional groups in their acyl chains [50].…”

Ligand-Based Virtual Screening for Discovery of Indole Derivatives as Potent DNA Gyrase ATPase Inhibitors Active against Mycobacterium tuberculosis and Hit Validation by Biological Assays

“…However, optimization of a lead compound, involving selection of structural modifications followed by synthesis and biological assay, can be both time-consuming and budget-intensive. In contrast, virtual screening can be a cost-effective and time-saving technique for discovery of new compounds. − This approach has been successfully used to identify multiple candidate anti-tuberculosis agents including inhibitors of PknB, PknG, DprE1, MurB, RpfB, DXPS, PimA, and CtpF. − Based on these promising previous findings, the indole derivative G24 was utilized as the starting template for structural similarity searches, constituting the initial step in the virtual screening approach used in the present work. These identified multiple candidate ATPase inhibitors from the compound library of the Specs database (www.specs.net).…”