000168221 001__ 168221
000168221 005__ 20260219141450.0
000168221 0247_ $$2doi$$a10.1007/s11030-025-11448-4
000168221 0248_ $$2sideral$$a147731
000168221 037__ $$aART-2026-147731
000168221 041__ $$aeng
000168221 100__ $$aLuong, Manh-Tu
000168221 245__ $$aFRAIL: fragment-based reinforcement learning for molecular design and benchmarking on fatty acid amide hydrolase 1 (FAAH-1)
000168221 260__ $$c2026
000168221 5203_ $$aWe propose FRAIL (Fragment-based Reinforcement Learning for Inhibitors), a generative AI framework that integrates fragment-based molecular design, multi- objective reinforcement learning, and molecular modeling to accelerate inhibitor discovery. Several deep generative models were fine-tuned on FAAH-1 (Fatty Acid Amide Hydrolase 1)–specific dataset and systematically benchmarked, with the best-performing model incorporated into FRAIL. The framework employs a customized reward function that jointly optimizes physicochemical properties and predicted bioactivity (pIC50) to guide molecular generation toward FAAH- favorable chemotypes. FRAIL generated structurally novel, fragment-grown compounds exhibiting high predicted binding affinity, desirable drug-likeness, and synthetic accessibility. These findings demonstrate FRAIL’s capability to enhance rational drug design and provide a reproducible pipeline for the discovery of experimentally viable FAAH inhibitors.
000168221 540__ $$9info:eu-repo/semantics/closedAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000168221 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000168221 700__ $$aPham, Khanh Huyen Thi
000168221 700__ $$aNguyen, Nhat-Hai
000168221 700__ $$aLe, Van-Tuan
000168221 700__ $$aPham, Phu Tran Vinh
000168221 700__ $$aNguyen, Tan Khanh
000168221 700__ $$aNguyen, Thi-Thu$$uUniversidad de Zaragoza
000168221 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000168221 773__ $$pMol. divers.$$tMOLECULAR DIVERSITY$$x1381-1991
000168221 8564_ $$s2476429$$uhttps://zaguan.unizar.es/record/168221/files/texto_completo.pdf$$yVersión publicada
000168221 8564_ $$s2263659$$uhttps://zaguan.unizar.es/record/168221/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000168221 909CO $$ooai:zaguan.unizar.es:168221$$particulos$$pdriver
000168221 951__ $$a2026-02-19-14:14:15
000168221 980__ $$aARTICLE