Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Structure. 2011 Apr 13;19(4):555-65. doi: 10.1016/j.str.2011.01.014.
Binding-induced backbone and large-scale conformational changes represent one of the major challenges in the modeling of biomolecular complexes by docking. To address this challenge, we have developed a flexible multidomain docking protocol that follows a "divide-and-conquer" approach to model both large-scale domain motions and small- to medium-scale interfacial rearrangements: the flexible binding partner is treated as an assembly of subparts/domains that are docked simultaneously making use of HADDOCK's multidomain docking ability. For this, the flexible molecules are cut at hinge regions predicted using an elastic network model. The performance of this approach is demonstrated on a benchmark covering an unprecedented range of conformational changes of 1.5 to 19.5 Å. We show from a statistical survey of known complexes that the cumulative sum of eigenvalues obtained from the elastic network has some predictive power to indicate the extent of the conformational change to be expected.
结合诱导的骨架和大规模构象变化是通过对接对生物分子复合物进行建模的主要挑战之一。为了解决这个挑战，我们开发了一种灵活的多域对接协议，该协议采用“分而治之”的方法来模拟大规模的结构域运动和小到中等规模的界面重排：将柔性结合配偶体视为亚部分/结构域的组装，这些亚部分/结构域同时进行对接，利用 HADDOCK 的多域对接能力。为此，使用弹性网络模型预测的铰链区域对柔性分子进行切割。该方法的性能在一个基准测试中得到了验证，该基准测试涵盖了前所未有的 1.5 到 19.5 Å 的构象变化范围。我们从对已知复合物的统计调查中表明，从弹性网络中获得的特征值总和具有一定的预测能力，可以指示预期的构象变化程度。
