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Dryad

Folding-unfolding asymmetry and a RetroFold computational algorithm

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Dec 19, 2022 version files 5.64 KB

Abstract

We treat protein folding as the molecular self-assembly, while unfolding is viewed as disassembly. Self-assembly and disassembly (fracture) are two opposite non-equilibrium dynamic processes; however, they cannot be converted to each other by a simple time variable reversal. Fracture is typically a much faster process than self-assembly. Self-assembly is often an exponentially decaying process, since energy relaxes due to dissipation, while fracture may be a constant rate process as the driving force is opposed by damping. Typically, protein folding takes two orders of magnitude longer time than unfolding, and it consumes a lot of computational resources to model folding. Based on energy dissipation rates, we suggest a mathematical transformation of variables, which makes it possible to view self-assembly as time-reversed disassembly, thus folding can be studied as reversed unfolding. We investigate the molecular dynamics modeling of folding and unfolding of the short Trp-cage protein. Folding time constitutes about 800 ns while unfolding (denaturation) takes only about 5.0 ns, and therefore, fewer computational resources are needed for its simulation. This “RetroFold” approach can be used for the design of a novel computation algorithm, which, while approximate, is less time-consuming than traditional folding algorithms.