Stabilization of the native protein structure in nanoscale confinement is important both for in vivo processes, such as chaperonin-assisted folding, and for bioengineering applications. To understand kinetic requirements for folding of multi-domain proteins in confinement, we perform coarse-grained Langevin dynamics simulations of actin within single-walled carbon nanotubes. Actin comprises two non-contiguous domains and its folding is strictly dependent on the eukaryotic chaperonin CCT. Our bulk folding simulations show that the difficulty in forming long-distance native contacts precludes actin from folding spontaneously. By contrast, weak confinement promotes folding and enhances the overall stability of the native structure of actin, while moderate confinement does not lead to enhancement of the native yield. Folding of quasi-native actin structures in nanopores, which reproduces conditions relevant for chaperonin-assisted folding of this protein, is found to be optimal in the moderate confinement regime, while strong confinement results in a decrease of the native yield.

Computational studies of actin folding within cylindrical nanopores

244th National Meeting (2012)

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