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MINERALS |
3MT INTEGRATIVE GRADUATE EDUCATION AND RESEARCH TRAINING PROGRAM |
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METALS |
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METALLOIDS |
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TOXICITY |
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IGERT Trainees |
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Research Interests: A Computational Approach to DNA Damager and Repair My research interest concerns endogenous oxidative damage to DNA, specifically the 8-oxo-7,8,-dihydroguanine (8-oxoG) damaged base, and its repair by the Formamidopyrimidine-DNA glycosylase (Fpg) in the E. coli system. Reactive oxygen species cause 8-oxoguanine damage by oxidation of a normal guanine base, and these reactive species can be metal ions. Fpg is able to selectively recognize and excise this damage, by everting the 8-oxoguanine base from the helix into the enzyme’s active site, and cleaving it by nucleophilic substitution and subsequent beta and delta eliminations. However, x-ray crystallography can not show the eversion of the base or the subsequent excision, due to the low populated high-energy states of these pathways, thus requiring molecular dynamics to give a comprehensive picture of the Fpg mechanism. The characterization of this damage repair pathway, and its carcinogenic and mutagenic effects, has long been studied, and by applying molecular dynamics to this problem, we will better understand the way in which this enzyme efficiently repairs damage and conserves DNA sequence.
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