title: Molecular Modeling on Berberine Derivatives toward BuChE: An Integrated Study with Quantitative Structure-Activity Relationships Models, Molecular Docking, and Molecular Dynamics Simulations.
abstract: A dataset of 67 berberine derivatives for the inhibition of butyrylcholinesterase (BuChE) was studied based on the combination of quantitative structure-activity relationships models, molecular docking, and molecular dynamics methods. First, a series of berberine derivatives were reported, and their inhibitory activities toward butyrylcholinesterase (BuChE) were evaluated. By 2D- quantitative structure-activity relationships studies, the best model built by partial least-square had a conventional correlation coefficient of the training set (R(2)) of 0.883, a cross-validation correlation coefficient (Qcv2) of 0.777, and a conventional correlation coefficient of the test set (Rpred2) of 0.775. The model was also confirmed by Y-randomization examination. In addition, the molecular docking and molecular dynamics simulation were performed to better elucidate the inhibitory mechanism of three typical berberine derivatives (berberine, C2, and C55) toward BuChE. The predicted binding free energy results were consistent with the experimental data and showed that the van der Waals energy term (ΔEvdw) difference played the most important role in differentiating the activity among the three inhibitors (berberine, C2, and C55). The developed quantitative structure-activity relationships models provide details on the fine relationship linking structure and activity and offer clues for structural modifications, and the molecular simulation helps to understand the inhibitory mechanism of the three typical inhibitors. In conclusion, the results of this study provide useful clues for new drug design and discovery of BuChE inhibitors from berberine derivatives.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.|Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510006, China.
authors.forename: Jiansong
authors.initials: J
authors.lastname: Fang
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Xiaocong
authors.initials: X
authors.lastname: Pang
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yan
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Lian
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510006, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.|Beijing Key Laboratory of Drug Target and Screening Research, Beijing, 100050, China.|State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China.
authors.forename: Ai-lin
authors.initials: AL
authors.lastname: Liu
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.|Beijing Key Laboratory of Drug Target and Screening Research, Beijing, 100050, China.|State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China.
authors.forename: Guan-hua
authors.initials: GH
authors.lastname: Du
mesh_terms: D001599:Berberine / Q000737:chemistry*; D002091:Butyrylcholinesterase / Q000737:chemistry*; D000069550:Machine Learning; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D013329:Structure-Activity Relationship
chemical_list: D001599:Berberine; D002091:Butyrylcholinesterase
keywords: berberine derivatives; butyrylcholinesterase; molecular dynamics simulation; quantitative structure-activity relationships models