DNA and estrogen receptor interaction revealed by fragment molecular orbital calculations
Abstract
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…
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