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Abstract：
Among the long-standing efforts to elucidate the physical mechanisms of protein-ligand catch bonding, particular attention has been directed at the family of selectin proteins. Selectins exhibit slip, catch-slip, and slip-catch-slip bonding, with minor structural modifications causing major changes in selectins\' response to force. How can a single structural mechanism allow interconversion between these various behaviors? We present a unifying theory of selectin-ligand catch bonding, using a structurally motivated free energy landscape to show how the topology of force-induced deformations of the molecular system produces the full range of observed behaviors. We find that the pathway of bond rupture deforms in non-trivial ways, such that unbinding dynamics depend sensitively on force. This implies a severe breakdown of Bell\'s theory-a paradigmatic theory used widely in catch bond modeling-raising questions about the suitability of Bell\'s theory in modeling other catch bonds. Our approach can be applied broadly to other protein-ligand systems.
摘要：
在阐明蛋白质-配体捕获键的物理机制的长期努力中，特别关注的是选择蛋白家族。选择器表现出滑移，卡滑,和滑移-卡滞-滑移粘合，具有较小的结构修改，导致选择素对力的反应发生重大变化。单个结构机制如何允许这些不同行为之间的相互转换？我们提出了选择素-配体捕获键的统一理论，使用结构动机的自由能景观来显示分子系统的力引起的变形的拓扑结构如何产生全方位的观察到的行为。我们发现键断裂的途径以不平凡的方式变形，因此，解除束缚动力学敏感地依赖于力。这意味着贝尔理论的严重崩溃。贝尔理论是一种广泛用于捕捞债券建模的范式理论，引发了有关贝尔理论在其他捕捞债券建模中的适用性的问题。我们的方法可以广泛应用于其他蛋白质-配体系统。
