Computational Modeling of
DNA Binding Molecules
Charles Brian Kelly
Department of Chemistry and Biochemistry
University of North Carolina Wilmington
Wilmington, NC 28403
Me-Lex: A DNA damaging agent
 Me-Lex binds in the minor groove
of DNA
 Me-Lex causes specific DNA
damage resulting in the death of
the cell without any mutations
 Me-Lex has potential application in
cancer chemotherapy
Molecules being prepared in our laboratory
Objectives
 Develop Computational Method of Analysis
 Identify Linkers which are favorable for DNA
Binding
 Identify Linkers which do not favor DNA Binding
 Identify what compounds are good candidates for
synthesis in the laboratory
Methods
 Import structure from
protein data bank into
computational program
(Insight II)
 Modify structure to
represent compounds
for project
Crystal structure imported from
Brookhaven protein data bank
Methods (cont.)
 Subject modified structure to
molecular dynamics calculations
(AMBER)
 Calculations indicate whether
new structure energetically
favorable or not
 Calculations are being
conducted in collaboration with
Dr. Lee Bartolotti (ECU) using
SGI Origin 350 High
Performance Computer
Me-Lex with attached linker and glucose
ring (modified in INSIGHT II)
Preliminary Work
 14 different modified structures have been
created using INSIGHTII
 Parameters have been defined for Me-Lex
 Molecular dynamics calculations have been
initiated on one compound
ACKNOWLEDGEMENTS:
 Dr. Sridhar Varadarajan
 Dr. Libero Bartolotti ( East Carolina
University)
 Dr. Ned Martin
 Heather Hill
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