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1. Long-lived metastable knots in polyampholyte chains

   https://doi.org/10.1371/journal.pone.0287200  

   Ozmaian, Masoumeh; Makarov, Dmitrii E. (June 2023, PLOS ONE)

   Yong, Xin (Ed.)

   Knots in proteins and DNA are known to have significant effect on their equilibrium and dynamic properties as well as on their function. While knot dynamics and thermodynamics in electrically neutral and uniformly charged polymer chains are relatively well understood, proteins are generally polyampholytes, with varied charge distributions along their backbones. Here we use simulations of knotted polymer chains to show that variation in the charge distribution on a polyampholyte chain with zero net charge leads to significant variation in the resulting knot dynamics, with some charge distributions resulting in long-lived metastable knots that escape the (open-ended) chain on a timescale that is much longer than that for knots in electrically neutral chains. The knot dynamics in such systems can be described, quantitatively, using a simple one-dimensional model where the knot undergoes biased Brownian motion along a “reaction coordinate”, equal to the knot size, in the presence of a potential of mean force. In this picture, long-lived knots result from charge sequences that create large electrostatic barriers to knot escape. This model allows us to predict knot lifetimes even when those times are not directly accessible by simulations. 

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2. The second Vassiliev measure of uniform random walks and polygons in confined space

   https://doi.org/10.1088/1751-8121/ac4abf  

   Smith, Philip; Panagiotou, Eleni (February 2022, Journal of Physics A: Mathematical and Theoretical)

   Abstract Biopolymers, like chromatin, are often confined in small volumes. Confinement has a great effect on polymer conformations, including polymer entanglement. Polymer chains and other filamentous structures can be represented by polygonal curves in three-space. In this manuscript, we examine the topological complexity of polygonal chains in three-space and in confinement as a function of their length. We model polygonal chains by equilateral random walks in three-space and by uniform random walks (URWs) in confinement. For the topological characterization, we use the second Vassiliev measure. This is an integer topological invariant for polygons and a continuous functions over the real numbers, as a function of the chain coordinates for open polygonal chains. For URWs in confined space, we prove that the average value of the Vassiliev measure in the space of configurations increases as O ( n 2 ) with the length of the walks or polygons. We verify this result numerically and our numerical results also show that the mean value of the second Vassiliev measure of equilateral random walks in three-space increases as O ( n ). These results reveal the rate at which knotting of open curves and not simply entanglement are affected by confinement. 

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3. The protein folding rate and the geometry and topology of the native state

   https://doi.org/10.1038/s41598-022-09924-0  

   Wang, Jason; Panagiotou, Eleni (April 2022, Scientific Reports)

   Abstract Proteins fold in 3-dimensional conformations which are important for their function. Characterizing the global conformation of proteins rigorously and separating secondary structure effects from topological effects is a challenge. New developments in applied knot theory allow to characterize the topological characteristics of proteins (knotted or not). By analyzing a small set of two-state and multi-state proteins with no knots or slipknots, our results show that 95.4% of the analyzed proteins have non-trivial topological characteristics, as reflected by the second Vassiliev measure, and that the logarithm of the experimental protein folding rate depends on both the local geometry and the topology of the protein’s native state. 

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4. A Topological Selection of Folding Pathways from Native States of Knotted Proteins

   https://doi.org/10.3390/sym13091670  

   Barbensi, Agnese; Yerolemou, Naya; Vipond, Oliver; Mahler, Barbara I.; Dabrowski-Tumanski, Pawel; Goundaroulis, Dimos (September 2021, Symmetry)

   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. 

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5. A first proof of knot localization for polymers in a nanochannel

   https://doi.org/10.1088/1751-8121/ad6c01  

   Beaton, Nicholas R; Ishihara, Kai; Atapour, Mahshid; Eng, Jeremy W; Vazquez, Mariel; Shimokawa, Koya; Soteros, Christine E (August 2024, Journal of Physics A: Mathematical and Theoretical)

   Abstract Based on polymer scaling theory and numerical evidence, Orlandini, Tesi, Janse van Rensburg and Whittington conjectured in 1996 that the limiting entropy of knot-typeKlattice polygons is the same as that for unknot polygons, and that the entropic critical exponent increases by one for each prime knot in the knot decomposition ofK. This Knot Entropy (KE) conjecture is consistent with the idea that for unconfined polymers, knots occur in a localized way (the knotted part is relatively small compared to polymer length). For full confinement (to a sphere or box), numerical evidence suggests that knots are much less localized. Numerical evidence for nanochannel or tube confinement is mixed, depending on how the size of a knot is measured. Here we outline the proof that the KE conjecture holds for polygons in the $\mathrm{\infty }\times 2\times 1$lattice tube and show that knotting is localized when a connected-sum measure of knot size is used. Similar results are established for linked polygons. This is the first model for which the knot entropy conjecture has been proved. 

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