Tom Connor Bishop, Dorina Kosztin, and Klaus Schulten.
How hormone receptor-DNA binding affects nucleosomal DNA: The
role of symmetry.
Biophysical Journal, 72:2056-2067, 1997.
(PMC: 1184400)
BISH97
Molecular dynamics simulations have been employed to determine the optimal conformation of an estrogen receptor DNA binding domain dimer bound to a consensus response element, ds(AGGTCACAGTGACCT), and to a non-consensus response element, ds(AGAACACAGTGACCT). The structures simulated were derived from a crystallographic structure and solvated by a sphere (45Åradius) of explicit water and counterions. Long range electrostatic interactions were accounted for during 100 ps simulations by means of a fast multipole expansion algorithm combined with a multiple time step scheme in the molecular dynamics package NAMD. The simulations demonstrate that the dimer induces a bent and underwound (10.7 bp/turn) conformation in the DNA. The bending reflects the dyad symmetry of the receptor dimer and can be described as an ``S"-shaped curve in the helical axis DNA when projected into a plane. A similar bent and underwound conformation is observed for nucleosomal DNA near the nucleosome's dyad axis that reflects the symmetry of the histone octamer. We propose that when a receptor dimer binds to a nucleosome the most favorable dimer-DNA and histone-DNA interactions are achieved if the respective symmetry axes are aligned. Such positioning of a receptor dimer over the dyad of nucleosome B in the mouse mammary tumor virus promoter is in agreement with experiment.
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