A topological selection of folding pathways from native states of knotted proteins

arXiv2104.10530MaRDI QIDQ6365810FDOQ6365810

Naya Yerolemou, Pawel Dabrowski-Tumanski, Dimos Goundaroulis, Oliver Vipond, Barbara I. Mahler, Agnese Barbensi

Publication date: 21 April 2021

Abstract: Understanding the biological function of knots in proteins and their folding process is an open and challenging question in biology. Recent studies classify the topology and geometry of knotted proteins by analysing the distribution of a protein's planar projections using topological objects called knotoids. We approach the analysis of proteins with the same topology by introducing a topologically inspired statistical metric between their knotoid distributions. We detect geometric differences between trefoil proteins by characterising their entanglement and we recover a clustering by sequence similarity. By looking directly at the geometry and topology of their native states, we are able to probe different folding pathways for proteins forming open-ended trefoil knots. Interestingly, our pipeline reveals that the folding pathway of shallow knotted Carbonic Anhydrases involves the creation of a double-looped structure, differently from what was previously observed for deeply knotted trefoil proteins. We validate this with Molecular Dynamics simulations.

Has companion code repository: https://github.com/nyerolemou/proteins-knotoEMD

Mathematics Subject Classification ID

Computational methods for problems pertaining to biology (92-08) General biology and biomathematics (92B05) Knot theory (57K10) Generalized knots (virtual knots, welded knots, quandles, etc.) (57K12)

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