title: Backbone hydration determines the folding signature of amino acid residues.
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.
authors: †SIB Swiss Institute of Bioinformatics and ‡Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
authors: Olivier
authors: O
authors: Bignucolo
authors: †SIB Swiss Institute of Bioinformatics and ‡Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
authors: Hoi Tik Alvin
authors: HT
authors: Leung
authors: †SIB Swiss Institute of Bioinformatics and ‡Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
authors: Stephan
authors: S
authors: Grzesiek
authors: †SIB Swiss Institute of Bioinformatics and ‡Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
authors: Simon
authors: S
authors: Bernèche
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D014867:Water / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D009842:Oligopeptides; D014867:Water