Computational Structural Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India.
Sci Rep. 2018 Jul 12;8(1):10546. doi: 10.1038/s41598-018-28373-2.
Protein-RNA recognition often induces conformational changes in binding partners. Consequently, the solvent accessible surface area (SASA) buried in contact estimated from the co-crystal structures may differ from that calculated using their unbound forms. To evaluate the change in accessibility upon binding, we compare SASA of 126 protein-RNA complexes between bound and unbound forms. We observe, in majority of cases the interface of both the binding partners gain accessibility upon binding, which is often associated with either large domain movements or secondary structural transitions in RNA-binding proteins (RBPs), and binding-induced conformational changes in RNAs. At the non-interface region, majority of RNAs lose accessibility upon binding, however, no such preference is observed for RBPs. Side chains of RBPs have major contribution in change in accessibility. In case of flexible binding, we find a moderate correlation between the binding free energy and change in accessibility at the interface. Finally, we introduce a parameter, the ratio of gain to loss of accessibility upon binding, which can be used to identify the native solution among the flexible docking models. Our findings provide fundamental insights into the relationship between flexibility and solvent accessibility, and advance our understanding on binding induced folding in protein-RNA recognition.
蛋白质与 RNA 的相互作用通常会引起结合配偶体构象的变化。因此，根据共晶结构估算的结合伴侣的溶剂可及表面积（SASA）可能与根据其非结合形式计算的表面积不同。为了评估结合前后的可及性变化，我们比较了 126 个蛋白质-RNA 复合物在结合和非结合形式下的 SASA。我们观察到，在大多数情况下，两个结合伴侣的界面在结合后都具有可及性，这通常与 RNA 结合蛋白（RBPs）的大结构域运动或二级结构转变以及 RNA 的结合诱导构象变化有关。在非界面区域，大多数 RNA 在结合后丧失了可及性，然而，RBPs 则没有这种趋势。RBPs 的侧链在可及性变化中起主要作用。对于灵活的结合，我们发现结合自由能与界面处可及性变化之间存在中等相关性。最后，我们引入了一个参数，即结合前后可及性增加与减少的比率，该参数可用于从灵活对接模型中识别天然溶液。我们的研究结果为理解灵活性和溶剂可及性之间的关系提供了基础，并深入了解了蛋白质-RNA 识别中的结合诱导折叠。
