Backbone hydration determines the folding signature of amino acid residues.


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.

DOI: 10.1021/jacs.5b00660

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@article{Bignucolo2015BackboneHD, title={Backbone hydration determines the folding signature of amino acid residues.}, author={Olivier Bignucolo and Hoi Tik Alvin Leung and Stephan Grzesiek and Simon Bern{\`e}che}, journal={Journal of the American Chemical Society}, year={2015}, volume={137 13}, pages={4300-3} }