title: QSAR modeling of globulin binding affinity of corticosteroids using AM1 calculations.
abstract: A quantitative structure-activity analysis of binding affinity of a series of 30 steroids for corticosteroid-binding globulin was performed using Wang-Ford charges of the non-hydrogen common atoms obtained from molecular electrostatic potential surface of AM1 optimized energy-minimized geometries of the compounds. Attempts were made to include lipophilicity (logP) and molar refractivity (MR) values of the whole molecules in the multivariate relations. The final relations were subjected to 'leave-one-out' cross-validation to check their predictive potential. It was found from the study that the charges of different atoms of the steroid nucleus [atoms 3, 4, 5 (ring A), 8, 9 (fusion points of rings B and C) and 16 (ring D)] contribute significantly to the binding affinity. This suggests the importance of these atoms/sites for the globulin binding affinity, which is also supported by previous reports on structure-activity relations of corticosteroids. Further, molar refractivity shows parabolic relation with the binding affinity, which indicates the possibility of dispersion interactions. The statistical qualities of the final equations generated in the present study (predicted variance 77-82%; explained variance 83-87%) are better than those of some of the previously reported models.
authors.affiliation: Drug Theoretics and Cheminformatics Lab, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Calcutta 700 032, India.
authors.forename: Kakali
authors.initials: K
authors.lastname: De
authors.forename: Chandana
authors.initials: C
authors.lastname: Sengupta
authors.forename: Kunal
authors.initials: K
authors.lastname: Roy
mesh_terms: D000305:Adrenal Cortex Hormones / Q000737:chemistry* / Q000494:pharmacology*; D005916:Globulins / Q000737:chemistry* / Q000378:metabolism; D008968:Molecular Conformation; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000305:Adrenal Cortex Hormones; D005916:Globulins