Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The atomic scale process by which proteins fold into their functional forms in aqueous solutions is still not well understood. While there is clearly an interplay between the sequence of the protein and the surrounding water solvent that leads to highly specific and reproducible folding in nature, there is still an ongoing debate concerning how water molecules aid in driving the folding process. By using a combination of techniques that provide information at the atomic level-neutron and X-ray diffraction and computer simulations-the mechanism of folding in a series of peptides that only vary with respect to the central side-chain residue has been determined. Specifically, β-turn formation for the KGXGK peptide (where X = P, G, S or L) occurs via a two-step water-driven attraction between specific sites on the peptide backbone. This proposed mechanism suggests that the site-specific hydration of the backbone facilitates the initial stages of protein folding and that this hydration interaction in combination with the presence of proline in the i + 1 position helps to stabilize the folded and intermediate folding state of the peptide in solution, leading to a greater propensity for PG containing sequences to occur in β-turns in proteins.

Original publication

DOI

10.1021/jacs.8b03643

Type

Journal article

Journal

J Am Chem Soc

Publication Date

13/06/2018

Volume

140

Pages

7301 - 7312