Self-organizing molecular field analysis on human β-secretase nonpeptide inhibitors: 5, 5-disubstituted aminohydantoins

► 3D-QSAR SOMFA model of 5, 5-disubstituted aminohydantoin derivatives for BACE-1 nonpeptide inhibitors was constructed. ► The statistical results have good non-cross-validated r2 (0.842), cross-validated q2 (0.792), F-test value (254.75) and satisfied predictive ability r2pred (0.721). ► Four different alignments and two charge-assigning methods were investigated. Among the four alignment method, superposition of docked conformations give the best results. Further alignment of docked conformation by aminohydantoin scaffold may slightly degenerate the SOMFA model. ► If the active ligand conformation was available, construction of other derivatives by using the ligand as template is more appropriate.