Transient knots in intrinsically disordered proteins and neurodegeneration.

We provide a brief overview of the topological features found in structured proteins and of the dynamical processes that involve knots. We then discuss the knotted states that arise in the intrinsically disordered polyglutamine and α-synuclein. We argue that the existence of the knotted conformations stalls degradation by proteases and thus enhances aggregation. This mechanism works if the length of a peptide chain exceeds a threshold, as in the Huntington disease. We also study the cavities that form within the conformations of the disordered proteins. The volume of the cavities varies in time in a way that is different than that of the radius of gyration or the end-to-end distance. In addition, we study the traffic between the conformational basins and identify patterns associated with the deep and shallow knots. The results are obtained by molecular dynamics simulations that use coarse-grained and all-atom models (with and without the explicit solvent).