Chemistry Department, Lomonosov Moscow State University, 119991 Moscow, Russia.
Molecules. 2019 Apr 11;24(7):1443. doi: 10.3390/molecules24071443.
Many nucleic acid-protein structures have been resolved, though quantitative structure-activity relationship remains unclear in many cases. Thrombin complexes with G-quadruplex aptamers are striking examples of a lack of any correlation between affinity, interface organization, and other common parameters. Here, we tested the hypothesis that affinity of the aptamer-protein complex is determined with the capacity of the interface to dissipate energy of binding. Description and detailed analysis of 63 nucleic acid-protein structures discriminated peculiarities of high-affinity nucleic acid-protein complexes. The size of the amino acid sidechain in the interface was demonstrated to be the most significant parameter that correlates with affinity of aptamers. This observation could be explained in terms of need of efficient energy transfer from interacting residues. Application of energy dissipation theory provided an illustrative tool for estimation of efficiency of aptamer-protein complexes. These results are of great importance for a design of efficient aptamers.
许多核酸-蛋白质结构已经得到解析，但在许多情况下，定量结构-活性关系仍不清楚。凝血酶与 G-四链体适体的复合物就是一个缺乏亲和力、界面组织和其他常见参数之间任何相关性的显著例子。在这里，我们测试了这样一个假设，即适体-蛋白质复合物的亲和力是由界面耗散结合能的能力决定的。对 63 个核酸-蛋白质结构的描述和详细分析，区分了高亲和力核酸-蛋白质复合物的特点。界面中氨基酸侧链的大小被证明是与适体亲和力最相关的重要参数。这一观察结果可以用需要从相互作用的残基中有效传递能量来解释。能量耗散理论的应用提供了一种估计适体-蛋白质复合物效率的说明性工具。这些结果对于设计高效适体具有重要意义。
