Identification of novel inhibitors for Prp protein of Mycobacterium tuberculosis by structure based drug design, and molecular dynamics simulations

In this study, we assess the effective inhibition of a series of thiazolidine derivatives (1a-1q) were adopting structure-based drug design. Thiazolidine is a five-membered ring structure with thioether and amino groups at positions 1 and 3. Although, thiazolidine may bind to a wide range of protein targets, it is a major heterocyclic core in medicinal chemistry. Different scoring utilities including AutoDock Vina, Glide, and MM/GBSA analysis were performed to commensurate the improvement of screening progress. The evaluated binding affinities were validated by molecular dynamics simulations over a period of 20 ns for the interactions between the Mycobacterium tuberculosis protein PrpR with three novel scaffolds (1b, 1j, and 1k). All the scaffolds exhibited distinct stable interactions with the significant residues like Arg169, Arg197, Tyr248, Arg308, and Gly311 respectively. Further, the inhibitory activities of scaffolds were predicted and evaluated by machine learning based algorithm to rank the above proposed compounds. This study reveals the potential of 1k and 1j as effective inhibitor candidates for the treatment of tuberculosis.