A Topological Selection of Folding Pathways from Native States of Knotted Proteins
A Topological Selection of Folding Pathways from Native States of Knotted Proteins
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DOI：
10.3390/sym13091670
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发表时间：
2021-09-01
期刊：
影响因子：
2.7
通讯作者：
Goundaroulis, Dimos
中科院分区：
文献类型：
--
作者：
Barbensi, Agnese;Yerolemou, Naya;Goundaroulis, Dimos
了解结蛋白如何折叠在生物学上是一个具有挑战性的问题。基于理论、模拟和实验，研究人员已经为它们的折叠路径提出了几个模型。具有相同结类型的蛋白质的几何形状可以有很大的不同，最近的模拟揭示了深结和浅结蛋白质的不同折叠行为。我们通过引入一种拓扑启发的统计度量来测量它们的纠缠来分析形成开放式三叶草结的蛋白质。通过直接观察其天然状态的几何和拓扑结构，我们能够探测这些蛋白质的不同折叠途径。特别是，浅结型碳酸酐酶的折叠途径涉及双环结构的产生，与其他结型三叶草蛋白相反。我们用分子动力学模拟验证了这一点。通过利用几何和局部对称性的打结蛋白的天然状态，我们提供了三叶草蛋白双环折叠机制的第一个数值证据。
Understanding how knotted proteins fold is a challenging problem in biology. Researchers have proposed several models for their folding pathways, based on theory, simulations and experiments. The geometry of proteins with the same knot type can vary substantially and recent simulations reveal different folding behaviour for deeply and shallow knotted proteins. We analyse proteins forming open-ended trefoil knots by introducing a topologically inspired statistical metric that measures their entanglement. By looking directly at the geometry and topology of their native states, we are able to probe different folding pathways for such proteins. In particular, the folding pathway of shallow knotted carbonic anhydrases involves the creation of a double-looped structure, contrary to what has been observed for other knotted trefoil proteins. We validate this with Molecular Dynamics simulations. By leveraging the geometry and local symmetries of knotted proteins' native states, we provide the first numerical evidence of a double-loop folding mechanism in trefoil proteins.