Local intersection volume: a new 3D descriptor applied to develop a 3D-QSAR pharmacophore model for benzodiazepine receptor ligands.
In this work, we have developed a new descriptor, named local intersection volume (LIV), in order to compose a 3D-QSAR pharmacophore model for benzodiazepine receptor ligands. The LIV can be classified as a 3D local shape descriptor in contraposition to the global shape descriptors. We have selected from the literature 49 non-benzodiazepine compounds as a training data set and the model was obtained and evaluated by genetic algorithms (GA) and partial least-squares (PLS) methods using LIVs as descriptors. The LIV 3D-QSAR model has a good predictive capacity according the cross-validation test by "leave-one-out" procedure (Q(2)=0.72). The developed model was compared to a comprehensive and extensive SAR pharmacophore model, recently proposed by Cook and co-workers, for benzodiazepine receptor ligands [J. Med. Chem. 43 (2000) 71]. It showed a relevant correlation with the pharmacophore groups pointed out in that work. Our LIV 3D-QSAR model was also able to predict affinity values for a series of nine compounds (test data set) that was not included into the training data set.
Verli
Hugo
H
Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Departamento de Fármacos, Faculdade de Farmácia, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, CP 68006, Rio de Janeiro, RJ 21944-970, Brazil.
Albuquerque
Magaly Girão
MG
Bicca de Alencastro
Ricardo
R
Barreiro
Eliezer J
EJ
D000465:Algorithms; D001665:Binding Sites; D003198:Computer Simulation; D020128:Inhibitory Concentration 50; D016018:Least-Squares Analysis; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D021281:Quantitative Structure-Activity Relationship; D011963:Receptors, GABA-A / Q000737:chemistry* / Q000378:metabolism*; D012984:Software; D055672:Static Electricity; D005680:gamma-Aminobutyric Acid / Q000737:chemistry* / Q000378:metabolism*
D008024:Ligands; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid