computational modeling of dna binding molecules
DESCRIPTION
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 - PowerPoint PPT PresentationTRANSCRIPT
Computational Modeling of DNA Binding Molecules
Charles Brian Kelly
Department of Chemistry and BiochemistryUniversity of North Carolina Wilmington
Wilmington, NC 28403
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
Me-Lex: A DNA damaging agent
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.)
Me-Lex with attached linker and glucose ring (modified in INSIGHT II)
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
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 VaradarajanDr. Sridhar Varadarajan
Dr. Libero Bartolotti ( East Carolina Dr. Libero Bartolotti ( East Carolina University)University)
Dr. Ned MartinDr. Ned Martin
Heather HillHeather Hill
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