Molecular dynamics simulations of the orientation of netropsin-DNA binding

BIOL 136

Ya-Yin Fang, yfang@howard.edu, Department of Biochemistry & Molecular Biology, Howard University College of Medicine, 520 W Street NW, Washington, DC 20059, Eric C. Long, long@chem.iupui.edu, Department of Chemistry & Chemical Biology, Indiana University-Purdue University Indianapolis, 402 North Blackford Street, Indianapolis, IN 46202, Vernon R. Morris, vmorris@howard.edu, Department of Chemistry, Howard University, 525 College Street NW, Washington, DC 20059, and William M. Southerland, wsoutherland@howard.edu, Department of Biochemistry and Molecular Biology, Howard University College of Medicine, 520 W Street, NW, Washington, DC 20059.
A great deal of experimental research has focused on the origins of the sequence selectivity of netropsin-DNA binding. In the work described herein, we employed molecular dynamics simulations to investigate the dynamic behavior and factors controlling the preferred binding orientations of netropsin to a 16 base pair oligonucleotide, d(CTTAATTCGAATTAAG)2. This oligonucleotide contains two A/T-rich netropsin binding sites in an asymmetric flanking sequence context and was co-crystallized recently with netropsin. We observe that netropsin is oriented distinctly in the available AATT binding sites with the guanidinium end adjacent to the dyad axis of the oligonucleotide. The implications of this work on the molecular recognition of DNA by netropsin and other minor groove binding agents will be discussed.
 

Chemistry and Metabolism
4:30 PM-6:30 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster

Division of Biological Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006