RECOGNITION OF DAMAGED DNA

我们正在检查DNA损伤的两个目标(1)与特定的 具有生物活性的病变；以及，(2)更好地了解 蛋白质与DNA的相互作用。具体地说，我们的重点是 化学诱变机制与DNA分子生物学 修理。我们建立了基于核磁共振的FPG锌指-DNA复合体的模型 和X-射线晶体结构。FPG的锌指部分是 基于XFIN的核磁共振结构。利用分子动力学和 螺旋面择优模式的组合库数据 链与DNA结合，我们评估了几种复杂的蛋白质-DNA 复合体。几百皮秒的分子动力学 包括溶剂和反离子，以完善我们的模型。 关键的氢键已经确定，我们正在测试我们的 使用定点突变的假说。

We are examining DNA damage for two goals (1) relating specific lesions with biological activity; and, (2) gain better understanding of protein-DNA interactions. Specifically, we are focusing on mechanisms of chemical mutagenesis and the molecular biology of DNA repair. We have modeled the FPG zinc finger-DNA complex based on NMR and X-ray crystallographic structures. The FPG zinc-finger moiety was based on the NMR structure of XFIN. Using molecular dynamics and combinatorial library data for preferential patterns of helix side chains binding to DNA, we evaluated several complex protein-DNA complexes. Several hundred picoseconds of molecular dynamics including solvent and counter-ions was performed to refine our model. Critical hydrogen bonds have been identified and we are testing our hypotheses using site specific mutagenesis.