Three-dimensional models of non-steroidal ligands: a comparative molecular field analysis.
The estrogen receptor, ER, is an important biological target whose inhibition is known to be therapeutically relevant in the treatment of postmenopausal osteoporosis. In the present study, two prediction methods (CoMFA and GRIND (Almond)) were used to describe the binding modes of a set of estrogen receptor ligands. The critical alignment step presented in CoMFA was solved by using the information of the molecular descriptors space generated by grid-independent descriptors (GRIND). Then, it was possible to build robust and high predictive models based on the alignment-independent model. Since the structure of estrogen receptor is solved, the results of the present 3D QSAR models, given by the PLS maps based on molecular interaction fields (MIF) were compared to ligand-binding ER domains and showed good agreement.
Menezes
Irwin R A
IR
Núcleo de Estudos em Química Medicinal-NEQUIM, Departamento de Química, Universidade Federal de Minas Gerais, Av. Pres. Antonio Carlos 6627, 31270-901 Belo Horizonte-MG, Brazil.
Leitão
Andrei
A
Montanari
Carlos A
CA
D001665:Binding Sites; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D003198:Computer Simulation; D004967:Estrogens / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D020849:Raloxifene Hydrochloride / Q000737:chemistry / Q000378:metabolism; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000378:metabolism*; D015203:Reproducibility of Results; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry* / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism
D004967:Estrogens; D008024:Ligands; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C016601:afimoxifene; D020849:Raloxifene Hydrochloride