Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA.
Campus Chemical Instrument Center, The Ohio State University, Columbus, OH, USA.
Bioinformatics. 2017 Jun 15;33(12):1814-1819. doi: 10.1093/bioinformatics/btx070.
Protein loops show rich conformational dynamics properties on a wide range of timescales as they play an essential role for many cellular functions during protein-protein interactions and recognition processes. However, little is known about the detail behavior of loops upon protein binding including allostery.
We report the loop motions and their dominant timescales for a library of 230 proteins that form protein-protein complexes using the ToeLoop predictor of loop dynamics. We applied the analysis to proteins in both their complex and free state and relate specific loop properties to their role in protein recognition. We observe a strong tendency of loops that move on relatively slow timescales of tens of ns to sub-μs to be directly involved in binding and recognition processes. Complex formation leads to a significant reduction in loop flexibility at the binding interface, but in a number of cases it can also trigger increased flexibility in distal loops in response to allosteric conformational changes. The importance of loop dynamics and allostery is highlighted by a case study of an antibody-antigen complex. Furthermore, we explored the relationship between loop dynamics and experimental binding affinities and found that a prevalence of high loop rigidity at the binding interface is an indicator of increased binding strength.
http://spin.ccic.ohio-state.edu/index.php/toeloopppi.
Supplementary data are available at Bioinformatics online.
蛋白质环在广泛的时间尺度上表现出丰富的构象动力学特性，因为它们在蛋白质-蛋白质相互作用和识别过程中发挥着许多细胞功能的重要作用。然而，对于环在蛋白质结合（包括变构）过程中的细节行为知之甚少。
我们使用 ToeLoop 环动力学预测器报告了 230 个形成蛋白质-蛋白质复合物的蛋白质库中所有环的运动及其主要时间尺度。我们将分析应用于蛋白质的复合物和自由状态，并将特定环的性质与其在蛋白质识别中的作用联系起来。我们观察到一个强烈的趋势，即那些在数十纳秒到亚微秒的相对较慢时间尺度上运动的环直接参与结合和识别过程。复合物的形成导致结合界面处环的柔韧性显著降低，但在许多情况下，它也可以触发远端环的柔韧性增加，以响应变构构象变化。环动力学和变构的重要性通过一个抗体-抗原复合物的案例研究得到了强调。此外，我们还探讨了环动力学与实验结合亲和力之间的关系，发现结合界面处高环刚性的普遍存在是结合强度增加的一个指标。
http://spin.ccic.ohio-state.edu/index.php/toeloopppi。
补充数据可在 Bioinformatics 在线获取。
