Identification of mycobacterial Thymidylate kinase inhibitors: a comprehensive pharmacophore, machine learning, molecular docking, and molecular dynamics simulation studies.

Thymidylate kinase (TMK) is a pivotal enzyme in Mycobacterium tuberculosis (Mtb), crucial for phosphorylating thymidine monophosphate (dTMP) to thymidine diphosphate (dTDP), thereby playing a critical role in DNA biosynthesis. Dysregulation or inhibition of TMK activity disrupts DNA replication and cell division, making it an attractive target for anti-tuberculosis drug development. In this study, the statistically validated pharmacophore mode was developed from a set of known TMK inhibitors.