Molecular dynamics of second-shell interactions in zinc finger binding sites

COMP 245

Megan L. Peach,, Basic Research Program, SAIC Frederick, Inc, National Cancer Institute, 376 Boyles Street, Frederick, MD 21702 and Marc C. Nicklaus,, Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Frederick, MD 21702.
Zinc finger domains bind zinc with a tetrahedral motif consisting of cysteine and histidine residues. These zinc binding sites are generally believed to have either a solely structural function, or to be redox-regulated. The solvent accessibility of the thiolate atoms in the zinc-binding cysteines, among other factors, influences their vulnerability to oxidation into disulfides, with concomitant release of zinc and domain unfolding. Second-shell interactions with positively charged residues surrounding the zinc binding site are important for stabilizing and shielding the negatively charged thiolate atoms. However, in a survey of NMR structures of the p300 transcription factor we have found significant differences in these second-shell interactions between different structures in the NMR ensemble. Here we present a series of molecular dynamics simulations of several different zinc fingers of various types. We explore the dynamics of the second shell interactions, and whether significant differences between structural zinc fingers and redox-regulated ones can be observed.

Poster Session
6:00 PM-8:00 PM, Tuesday, August 18, 2009 Walter E. Washington Convention Center -- Ballroom A, Poster

Division of Computers in Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009