DNA and estrogen receptor interaction revealed by fragment molecular orbital calculations

Toshio Watanabe, Yuichi Inadomi, Kaori Fukuzawa, Tatsuya Nakano, Shigenori Tanaka, Lennart Nilsson, Umpei Nagashima

研究成果: Article査読

38 被引用数 (Scopus)


Molecular orbital calculations of the complex between DNA-ERE (estrogen response element) and ER (estrogen receptor) - DBD (DNA-binding domain) were performed using the fragment molecular orbital (FMO) method, which enables large-scale MO (molecular orbital) calculations by reducing the computational cost and by significantly increasing efficiency for parallel computation. Such a large system, which contains 3354 atoms, is impractical via conventional MO methods due to the immense computational cost. Details of the interaction between DNA-ERE and ER-DBD were revealed in this study as follows by using the FMO calculations to analyze the interfragment interaction energies (IFIEs) and the electrostatic potentials (ESPs). An area with a high positive ESP is identified on the DNA-binding side of ER - DBD and is the main driving force behind access to the DNA. The position of the ER-DBD monomer can be fixed on a phosphate group of DNA-ERE by the strong electrostatic interactions, whereas the rotation cannot be fixed. In contrast, both the position and rotation of the ER-DBD dimer can be fixed and can therefore form the stable (ER-DBD) 2⋯DNA - ERE complex. Dimerization of the ER - DBD monomers, each of which have a charge of +5 , is mainly due to large attractive interaction energies of the second Zn fragments. The base pairs in the consensus sequence of DNA-ERE interact only with the recognition helix located in the major groove due to the large shielding effect of the phosphate groups of DNA. The recognition helix has weaker interactions with the base pairs than the electrostatic interactions with the phosphate groups. Thus, the DNA-binding machinery of the ER - DBD dimer, which can secure the recognition helix in the major groove of DNA, is crucial for interactions between the recognition helix and base pairs.

ジャーナルJournal of Physical Chemistry B
出版ステータスPublished - 2007 8 16

ASJC Scopus subject areas

  • 物理化学および理論化学
  • 表面、皮膜および薄膜
  • 材料化学


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