The function of protein, RNA, and DNA is modulated by fast, dynamic exchanges between three‐dimensional conformations. Conformational sampling of biomolecules with exact and nullspace inverse kinematics, using rotatable bonds as revolute joints and noncovalent interactions as holonomic constraints, can accurately characterize these native ensembles. However, sampling biomolecules remains challenging owing to their ultra‐high dimensional configuration spaces, and the requirement to avoid (self‐) collisions, which results in low acceptance rates. Here, we present two novel mechanisms to overcome these limitations. First, we introduce temporary constraints between near‐colliding links. The resulting constraint varieties instantaneously redirect the search for collision‐free conformations, and couple motions between distant parts of the linkage. Second, we adapt a randomized Poisson‐disk motion planner, which prevents local oversampling and widens the search, to ultra‐high dimensions. Tests on several model systems show that the sampling acceptance rate can increase from 16% to 70%, and that the conformational coverage in loop modeling measured as average closeness to existing loop conformations doubled. Correlated protein motions identified with our algorithm agree with those from MD simulations. © 2018 Wiley Periodicals, Inc.

中文翻译：

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超高维分子构象空间中的无碰撞泊松运动规划

蛋白质、RNA 和 DNA 的功能由三维构象之间的快速、动态交换调节。具有精确和零空间逆运动学的生物分子构象采样，使用可旋转键作为旋转关节，使用非共价相互作用作为完整约束，可以准确地表征这些原生集合。然而，由于其超高维配置空间以及避免（自）碰撞的要求，对生物分子进行采样仍然具有挑战性，这导致了低接受率。在这里，我们提出了两种新的机制来克服这些限制。首先，我们在接近碰撞的链接之间引入临时约束。由此产生的约束变化会立即重定向对无碰撞构象的搜索，并在链接的远距离部分之间耦合运动。其次，我们采用随机泊松盘运动规划器，防止局部过采样并扩大搜索范围，以达到超高维度。对几个模型系统的测试表明，采样接受率可以从 16% 增加到 70%，并且在测量为与现有环构象的平均接近度时环建模中的构象覆盖率增加了一倍。用我们的算法确定的相关蛋白质运动与 MD 模拟的一致。© 2018 Wiley Periodicals, Inc. 用我们的算法确定的相关蛋白质运动与 MD 模拟的一致。© 2018 Wiley Periodicals, Inc. 用我们的算法确定的相关蛋白质运动与 MD 模拟的一致。© 2018 Wiley Periodicals, Inc.