Targeting allosteric binding site in methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) to identify natural product inhibitors via structure-based computational approach.

ABSTRACT: Cancer has been viewed as one of the deadliest diseases worldwide. Among various types of cancer, breast cancer is the most common type of cancer in women. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a promising druggable target and is overexpressed in cancerous cells, like, breast cancer. We conducted structure-based modeling on the allosteric site of the enzyme. Targeting the allosteric site avoids the problem of drug resistance. Pharmacophore modeling, molecular docking, HYDE assessment, drug-likeness, ADMET predictions, simulations, and free-energy calculations were performed. The RMSD, RMSF, RoG, SASA, and Hydrogen-bonding studies showed that seven candidates displayed stable behaviour. As per the literature, average superimposed simulated structures revealed a similar prote

SUBMITTER: Rana N 

PROVIDER: S-EPMC10593809 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature