Thermodynamic stability of polypeptides folding within modeled ribosomal exit tunnel: a density functional study.

The mechanism of polypeptide folding, especially for the formation of tertiary structures, within the ribosomal exit tunnel, remains one of the most important unsolved problems in biophysical chemistry and molecular biology. In this work, we use a density functional theory (DFT) to explore the polypeptide folding within a modified nanopore, which mimics the confined environment of ribosomal exit tunnel. Results indicate that too long polypeptides (N>100 cannot fold into a helix state within the nanopore, and the helix polypeptides favor folding into a negative coiled coil rather than a positive one, because the negative coiled coil has a lower grand potential than the positive one, and the polypeptide folding into the negative coiled coil therefore needs less driving force than the positive one. To fold into the positive coiled coil, the helix polypeptides must have a small minor radius or a short chain length, which provides helpful insights into the design of nanodevices for manipulating the positive coiled coil. In the presence of attractive interaction, helices need more driving force to fold into coiled coil. Importantly, we have also proposed a scaling relation to understand the folding behavior. The scaling relation gives a good estimate for the computational results, and provides a reasonable explanation for the folding behavior. In summary, it is expected that the proposed DFT approach and the scaling relation provide alternative means for the investigation of polypeptide folding in confined environment, and these impressive results could give useful insights into nascent polypeptide folding.