title: Self-organizing molecular field analysis on human β-secretase nonpeptide inhibitors: 5, 5-disubstituted aminohydantoins.
abstract: 5, 5-disubstituted aminohydantoins have been recently reported as potent and selective human β-secretase (BACE-1) inhibitors. Self-Organizing Molecular Field Analysis (SOMFA) is used to study the correlation between the molecular properties and biological activities of the 5, 5-disubstituted aminohydantoins inhibitors. Four different alignments and two charge-assigning methods were investigated. The model derived from the superposition of docked conformation with AM1 charge showed satisfied predictive ability, which has good non-cross-validated r(2) (0.842), cross-validated q(2) (0.792), F-test value (254.75) and satisfied predictive ability r(2)(pred) (0.721). Analysis of SOMFA model may provide some useful information in the design of BACE-1 inhibitors with better spectrum of activity.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan, PR China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Meng
authors.initials: M
authors.lastname: Zhou
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Ding
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006827:Hydantoins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D021281:Quantitative Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D006827:Hydantoins; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human