Incorporating the dynamic nature of biomolecules in the modeling of their complexes is a challenge, especially when the extent and direction of the conformational changes taking place upon binding is unknown. Estimating whether the binding of a biomolecule to its partner(s) occurs in a conformational state accessible to its unbound form ("conformational selection") and/or the binding process induces conformational changes ("induced-fit") is another challenge. We propose here a method combining conformational sampling using ClustENM-an elastic network-based modeling procedure-with docking using HADDOCK, in a framework that incorporates conformational selection and induced-fit effects upon binding. The extent of the applied deformation is estimated from its energetical costs, inspired from mechanical tensile testing on materials. We applied our pre- and post-docking sampling of conformational changes to the flexible multidomain protein-protein docking benchmark and a subset of the protein-DNA docking benchmark. Our ClustENM-HADDOCK approach produced acceptable to medium quality models in 7/11 and 5/6 cases for the protein-protein and protein-DNA complexes, respectively. The conformational selection (sampling prior to docking) has the highest impact on the quality of the docked models for the protein-protein complexes. The induced-fit stage of the pipeline (post-sampling), however, improved the quality of the final models for the protein-DNA complexes. Compared to previously described strategies to handle conformational changes, ClustENM-HADDOCK performs better than two-body docking in protein-protein cases but worse than a flexible multidomain docking approach. However, it does show a better or similar performance compared to previous protein-DNA docking approaches, which makes it a suitable alternative.

中文翻译：

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使用ClustENM和HADDOCK对蛋白-蛋白和蛋白-DNA系统进行构象变化的对接前和对接后采样。

将生物分子的动力学性质纳入其复合物的建模是一个挑战，特别是当未知结合时发生构象变化的程度和方向时。估计生物分子与其伴侣的结合是否以其未结合形式可接近的构象状态发生（“构象选择”）和/或结合过程诱导构象变化（“诱导适合”）是另一挑战。我们在这里提出一种在结合了构象选择和结合后诱导效应的框架中，结合使用基于ClustENM（基于弹性网络的建模过程）与使用HADDOCK进行对接的构象采样的方法。变形的程度是根据其高昂的成本估算出来的，该成本是受材料的机械拉伸试验启发而来的。我们将构象变化的对接前和对接后采样应用于灵活的多域蛋白质-蛋白质对接基准以及蛋白质-DNA对接基准的子集。我们的ClustENM-HADDOCK方法分别针对蛋白质/蛋白质和蛋白质-DNA复合物产生了7/11和5/6情况下的中等质量模型。构象选择（对接之前进行采样）对蛋白质-蛋白质复合物对接模型的质量影响最大。但是，管道的诱导拟合阶段（后采样）提高了蛋白质-DNA复合物最终模型的质量。与先前描述的处理构象变化的策略相比，ClustENM-HADDOCK在蛋白质-蛋白质情况下的性能优于两体对接，但比灵活的多域对接方法要差。然而，