We are thrilled to announce Anu Manhas from the Pandit Deendayal Energy University as the winner of the Scientific Challenge Summer 2022!
The project focused on the identification and validation of potential inhibitors against the methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) enzyme, which is a promising target for anticancer drugs. The study explores the allosteric binding site of MTHFD2 and its potential as a target for inhibiting the enzyme’s activity. Computational techniques, such as structure-based in silico methods, pharmacophore modeling, virtual screening, molecular docking, and molecular dynamics simulations, were employed to identify and evaluate hit molecules.
The research began with the collection of MTHFD2 protein-ligand complexes and the generation of pharmacophore models. Virtual screening was performed using natural product database consisting of 236,561 molecules. Molecular docking and HYDE assessment narrowed down the candidates to 72 molecules with good ligand efficiency. Druglikeness, pharmacokinetic, and ADMET studies further reduced the number to 20 molecules, and seven candidates were cherry-picked for subsequent MD simulation studies to investigate their stability and binding affinity. The results demonstrated that the selected natural product candidates stabilized protein conformations compared to the reference apo-protein. The synthesis of these compounds is in progress, and their anticancer potential will be evaluated in future studies.
Overall, the research utilizes computational approaches to identify potential inhibitors against MTHFD2 by targeting the allosteric binding site. The findings contribute to the understanding of the enzyme’s mechanism and hold promise for the development of novel anticancer drugs.
We extend our heartfelt congratulations to Anu Manhas for the outstanding achievements and wish good luck with present and future drug discovery projects supported by BioSolveIT products and applications.
You can read more about the project here.