Matches in SemOpenAlex for { <https://semopenalex.org/work/W3204827479> ?p ?o ?g. }
- W3204827479 endingPage "1362" @default.
- W3204827479 startingPage "1351" @default.
- W3204827479 abstract "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 ΔGFEP between ligands and their target, which were more consistent with the experimental binding potencies ΔGEXP (the mean absolute deviations |ΔGFEP−ΔGEXP| < 2 kcal/mol) than those ΔGMM-PBSA or ΔGMM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC50 of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery." @default.
- W3204827479 created "2021-10-11" @default.
- W3204827479 creator A5014015813 @default.
- W3204827479 creator A5023826377 @default.
- W3204827479 creator A5024894629 @default.
- W3204827479 creator A5034855502 @default.
- W3204827479 creator A5034916466 @default.
- W3204827479 creator A5050378982 @default.
- W3204827479 creator A5055339874 @default.
- W3204827479 creator A5056326026 @default.
- W3204827479 creator A5063091077 @default.
- W3204827479 creator A5074235217 @default.
- W3204827479 creator A5080915850 @default.
- W3204827479 date "2022-03-01" @default.
- W3204827479 modified "2023-10-16" @default.
- W3204827479 title "Free energy perturbation (FEP)-guided scaffold hopping" @default.
- W3204827479 cites W1549357029 @default.
- W3204827479 cites W1894396595 @default.
- W3204827479 cites W1968984443 @default.
- W3204827479 cites W1972561485 @default.
- W3204827479 cites W1976499671 @default.
- W3204827479 cites W1976874178 @default.
- W3204827479 cites W1985588649 @default.
- W3204827479 cites W2000456051 @default.
- W3204827479 cites W2000613080 @default.
- W3204827479 cites W2009423060 @default.
- W3204827479 cites W2009519688 @default.
- W3204827479 cites W2015612733 @default.
- W3204827479 cites W2017300875 @default.
- W3204827479 cites W2017829285 @default.
- W3204827479 cites W2018621056 @default.
- W3204827479 cites W2024762727 @default.
- W3204827479 cites W2028930776 @default.
- W3204827479 cites W2031372687 @default.
- W3204827479 cites W2035687084 @default.
- W3204827479 cites W2039562363 @default.
- W3204827479 cites W2056881083 @default.
- W3204827479 cites W2063831812 @default.
- W3204827479 cites W2067300585 @default.
- W3204827479 cites W2072604508 @default.
- W3204827479 cites W2075186867 @default.
- W3204827479 cites W2083961230 @default.
- W3204827479 cites W2086420082 @default.
- W3204827479 cites W2105103540 @default.
- W3204827479 cites W2107572441 @default.
- W3204827479 cites W2118233996 @default.
- W3204827479 cites W2121476216 @default.
- W3204827479 cites W2128572087 @default.
- W3204827479 cites W2140151763 @default.
- W3204827479 cites W2147993766 @default.
- W3204827479 cites W2159498044 @default.
- W3204827479 cites W2162106505 @default.
- W3204827479 cites W2164270482 @default.
- W3204827479 cites W2320513108 @default.
- W3204827479 cites W2552522590 @default.
- W3204827479 cites W2562257444 @default.
- W3204827479 cites W2567443601 @default.
- W3204827479 cites W2571178759 @default.
- W3204827479 cites W2613820968 @default.
- W3204827479 cites W2620296850 @default.
- W3204827479 cites W2729936595 @default.
- W3204827479 cites W2914266147 @default.
- W3204827479 cites W2926049480 @default.
- W3204827479 cites W2951690173 @default.
- W3204827479 cites W2952490839 @default.
- W3204827479 cites W2954094311 @default.
- W3204827479 cites W2959398146 @default.
- W3204827479 cites W3049717759 @default.
- W3204827479 cites W3092297806 @default.
- W3204827479 cites W3168417902 @default.
- W3204827479 cites W4230274588 @default.
- W3204827479 cites W4241743140 @default.
- W3204827479 doi "https://doi.org/10.1016/j.apsb.2021.09.027" @default.
- W3204827479 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35530128" @default.
- W3204827479 hasPublicationYear "2022" @default.
- W3204827479 type Work @default.
- W3204827479 sameAs 3204827479 @default.
- W3204827479 citedByCount "9" @default.
- W3204827479 countsByYear W32048274792023 @default.
- W3204827479 crossrefType "journal-article" @default.
- W3204827479 hasAuthorship W3204827479A5014015813 @default.
- W3204827479 hasAuthorship W3204827479A5023826377 @default.
- W3204827479 hasAuthorship W3204827479A5024894629 @default.
- W3204827479 hasAuthorship W3204827479A5034855502 @default.
- W3204827479 hasAuthorship W3204827479A5034916466 @default.
- W3204827479 hasAuthorship W3204827479A5050378982 @default.
- W3204827479 hasAuthorship W3204827479A5055339874 @default.
- W3204827479 hasAuthorship W3204827479A5056326026 @default.
- W3204827479 hasAuthorship W3204827479A5063091077 @default.
- W3204827479 hasAuthorship W3204827479A5074235217 @default.
- W3204827479 hasAuthorship W3204827479A5080915850 @default.
- W3204827479 hasBestOaLocation W32048274792 @default.
- W3204827479 hasConcept C136229726 @default.
- W3204827479 hasConcept C185592680 @default.
- W3204827479 hasConcept C21951064 @default.
- W3204827479 hasConcept C53645450 @default.
- W3204827479 hasConcept C55493867 @default.
- W3204827479 hasConcept C62478195 @default.