1.Free energy perturbation (FEP)-guided scaffold hopping.
Deyan WU ; Xuehua ZHENG ; Runduo LIU ; Zhe LI ; Zan JIANG ; Qian ZHOU ; Yue HUANG ; Xu-Nian WU ; Chen ZHANG ; Yi-You HUANG ; Hai-Bin LUO
Acta Pharmaceutica Sinica B 2022;12(3):1351-1362
Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies ΔG FEP between ligands and their target, which were more consistent with the experimental binding potencies ΔG EXP (the mean absolute deviations
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