CrossRef enabled

PAC Archives

Archive →

Pure Appl. Chem., 2003, Vol. 75, No. 11-12, pp. 2405-2410

Fragment molecular orbital study of the binding energy of ligands to the estrogen receptor

Kaori Fukuzawa, Kazuo Kitaura, K. Nakata, Tsuguchika Kaminuma and T. Nakano

Fuji Research Institute Corporation, 2-3 Kanda Nishiki-cho, Chiyoda-ku, Tokyo 101-8443, Japan; National Institute of Advanced Industrial Science and Technology, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan; National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan; Chem-Bio Informatics Society, 4-3-16 Yoga #301, Setagaya-ku, Tokyo 158-0097, Japan

Abstract: We examined the published data for the binding affinity of typical ligands to the α-subtype of the human estrogen receptor with use of an approximate molecular orbital method applicable to interacting molecular clusters. An ab initio procedure for "molecular fragments" proposed recently to deal with such macromolecules as proteins was applied to the molecular orbital calculations. The receptor protein was primarily modeled using 50 amino acid residues surrounding the ligand. For a few ligand-receptor complexes, the binding energy was also calculated with use of 241 amino acid residues contained in the entire binding domain. No significant difference was found in the calculated binding energy between the complex modeled with ligand-surrounding 50 amino acids and that with residues of the entire domain. The calculated binding energy was correlated very well with the published relative binding affinity for typical ligands.