Pastor N, Weinstein H, Jamison E, Brenowitz M
Facultad de Ciencias, UAEM, Av. Universidad 1001, Col. Chamilpa, Cuernavaca, Morelos, 62210, México.
J Mol Biol. 2000 Nov 17;304(1):55-68. doi: 10.1006/jmbi.2000.4173.
The hydroxyl radical footprint of the TATA-binding protein (TBP) bound to the high-affinity sequence TATAAAAG of the adenovirus 2 major late promoter has been quantitatively compared to a 2 ns molecular dynamics simulation of the complex in aqueous solution at room temperature using the CHARMM23 potential. The nucleotide-by-nucleotide analysis of the TBP-TATA hydroxyl radical footprint correlates with the solvent-accessible surface calculated from the dynamics simulation. The results suggest that local reactivity towards OH radicals results from the interplay between the local DNA geometry imposed by TBP binding, and the dynamics of the side-chains contacting the sugar hydrogen atoms. Analysis of the dynamics suggests that, over time, TBP forms stable interactions with the sugar-phosphate backbone through multiple contacts to different partners. This mechanism results in an enthalpic advantage to complex formation at a low entropic cost.
已将与腺病毒2主要晚期启动子的高亲和力序列TATAAAAG结合的TATA结合蛋白（TBP）的羟基自由基足迹，与使用CHARMM23势在室温下对该复合物在水溶液中的2纳秒分子动力学模拟进行了定量比较。TBP-TATA羟基自由基足迹的逐个核苷酸分析与动力学模拟计算出的溶剂可及表面相关。结果表明，对OH自由基的局部反应性源于TBP结合所施加的局部DNA几何形状与接触糖氢原子的侧链动力学之间的相互作用。动力学分析表明，随着时间的推移，TBP通过与不同伙伴的多次接触与糖磷酸主链形成稳定的相互作用。这种机制以低熵成本为复合物形成带来了焓优势。
