Session Y45: Focus Session: Physics of Cancer II
8:00 AM–11:00 AM, Friday, March 22, 2013
Hilton Baltimore Room: Holiday Ballroom 4
Sponsoring Unit:
DBIO
Chair: Larry Nagahara, National Institutes of Health
Abstract ID: BAPS.2013.MAR.Y45.8
Abstract: Y45.00008 : Non-covalent interactions of the carcinogen (+)-anti-BPDE with exon 1 of the human K-ras proto-oncogene
9:48 AM–10:00 AM
Preview Abstract
MathJax On | Off 
Abstract 
Authors:
Jorge H. Rodriguez
(Department of Physics, Purdue University)
Christos Deligkaris
(Department of Physics, Purdue University)
Investigating the complementary, but different, effects of physical (non-covalent) and chemical (covalent) mutagen-DNA and carcinogen-DNA interactions is important for understanding possible mechanisms of development and prevention of mutagenesis and carcinogenesis. A highly mutagenic and carcinogenic metabolite of the polycyclic aromatic hydrocarbon benzo[$\alpha$]pyrene, namely (+)-anti-BPDE, is known to undergo both physical and chemical complexation with DNA. The major covalent adduct, a promutagenic, is known to be an external (+)-trans-anti-BPDE-N$^2$-dGuanosine configuration whose origins are not fully understood. Thus, it is desirable to study the mechanisms of external non-covalent BPDE-DNA binding and their possible relationships to external covalent trans adduct formation. We present a detailed codon-by-codon computational study of the non-covalent interactions of (+)-anti-BPDE with DNA which explains and correctly predicts preferential (+)-anti-BPDE binding at minor groove guanosines. Due to its relevance to carcinogenesis, the interaction of (+)-anti-BPDE with exon 1 of the human K-ras gene has been studied in detail.
To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2013.MAR.Y45.8