Fragment molecular orbital study of the binding energy of ligands
to the estrogen receptor
K. Fukuzawa, K. Kitaura, K. Nakata, T. 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 a-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.
*Report from a SCOPE/IUPAC project: Implication of
Endocrine Active Substances for Human and Wildlife (J. Miyamoto and
J.Burger, editors). Other reports are published in this issue,
pp. 1617-2615.
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