Cresset unveils breakthrough in SARS-CoV-2 inhibitor identification
Leveraging Flare FEP for precise binding predictions
21 Aug 2023Product news
Cresset has introduced a pioneering approach to identifying potential inhibitors of SARS-CoV-2 Mpro cysteine protease. Leveraging the power of Flare™ free energy perturbation (FEP), a robust tool for binding affinity predictions, the study focuses on clarifying the binding affinity of compounds against Mpro and deciphering the crucial interactions that underpin potency.
The innovation centers on a hybrid DFT//GFN2-xTB approach, intertwining Density Functional Theory (DFT) and the extended semiempirical tight-binding model (GFN2-xTB) to tailor force field parameters for ligands. This amalgamation empowers the generation of customized parameters, elevating phase space sampling and redefining accuracy in molecular simulations.
By harnessing the relative free energies of binding (ΔΔG) via Flare FEP, the study effectively gauged the binding affinity of compounds to Mpro. This approach allowed Cresset Discovery to pinpoint 36 analogues with known activity against Mpro of SARS-CoV-2, and the subsequent FEP production run predicted 13 compounds to be substantially more potent than the starting point.
Cresset's success demonstrates the potential of synergy between Cresset tools and expert free energy methods in accelerating drug discovery. This approach holds promise in uncovering new drugs and revolutionizing the pace of research.