Coarse-Graining Reshapes Knot Dynamics in Polymers and Proteins

<jats:p>Coarse-grained (CG) molecular dynamics (MD) simulations offer an efficient route to explore long-timescale dynamics of knots in proteins and polymers. Despite extensive studies of knots using both atomistic (AA-) and CG-MD simulations, systematic comparisons of how coarse-graining alters knot relaxation mechanisms, intermediates, and timescales—particularly in melts and proteins—remain scarce. Here, we employ AAand CG-MD simulations to investigate the relaxation of tight knots in single polyethylene (PE) chains, PE-polymer melts, and a trefoil-knotted protein. Across all systems, CG models accelerate knot relaxation and enhance global mobility while preserving the dominant topological relaxation mechanism observed in AA-MD simulations. In single chains, CG-MD simulations produce smooth, monotonic unknotting trajectories, whereas AA-MD simulations reveal transient structural intermediates and intermittent shape rearrangements within the knot core. In melts, CG dynamics remain faster and more homogeneous, while AA polymers exhibit kinetically trapped intermediates and sliding-dominated relaxation driven by topological confinement. For the knotted protein, CG-MD simulations enable knot loosening and conformational rearrangements inaccessible on standard AA-MD timescales due to kinetic trapping. Collectively, these findings establish that coarse graining systematically accelerates topological relaxation by smoothing the effective energy landscape and suppressing short-lived metastable knot conformations, while the dominant relaxation pathway is preserved.</jats:p>