Computational Approaches to Identify Molecules Binding to Mycobacterium tuberculosis KasA.

ABSTRACT: Tuberculosis is caused by Mycobacterium tuberculosis (Mtb) and is a deadly disease resulting in the deaths of approximately 1.5 million people with 10 million infections reported in 2018. Recently, a key condensation step in the synthesis of mycolic acids was shown to require β-ketoacyl-ACP synthase (KasA). A crystal structure of KasA with the small molecule DG167 was recently described, which provided a starting point for using computational structure-based approaches to identify additional molecules binding to this protein. We now describe structure-based pharmacophores, docking and machine learning studies with Assay Central as a computational tool for the identification of small molecules targeting KasA. We then tested these compounds using nanoscale differential scanning fluori

SUBMITTER: Puhl AC 

PROVIDER: S-EPMC7689923 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature