Backbone hydration determines the folding signature of amino acid residues

Journal of the American Chemical Society
Olivier BignucoloSimon Bernèche

Abstract

The relation between the sequence of a protein and its three-dimensional structure remains largely unknown. A lasting dream is to elucidate the side-chain-dependent driving forces that govern the folding process. Different structural data suggest that aromatic amino acids play a particular role in the stabilization of protein structures. To better understand the underlying mechanism, we studied peptides of the sequence EGAAXAASS (X = Gly, Ile, Tyr, Trp) through comparison of molecular dynamics (MD) trajectories and NMR residual dipolar coupling (RDC) measurements. The RDC data for aromatic substitutions provide evidence for a kink in the peptide backbone. Analysis of the MD simulations shows that the formation of internal hydrogen bonds underlying a helical turn is key to reproduce the experimental RDC values. The simulations further reveal that the driving force leading to such helical-turn conformations arises from the lack of hydration of the peptide chain on either side of the bulky aromatic side chain, which can potentially act as a nucleation point initiating the folding process.

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Citations

Nov 3, 2015·Dalton Transactions : an International Journal of Inorganic Chemistry·Ilaria GambaMiguel Vázquez López
Mar 10, 2018·Physical Chemistry Chemical Physics : PCCP·Yeonjoon KimWoo Youn Kim
Nov 7, 2017·Molecular BioSystems·Harshavardhan KhareSuryanarayanarao Ramakumar
Sep 9, 2017·Protein Science : a Publication of the Protein Society·Yang ShenAd Bax
Aug 8, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Luigi Di Costanzo, Silvano Geremia
May 29, 2018·Journal of the American Chemical Society·Nicola SteinkeSylvia E McLain

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