Backbone hydration determines the folding signature of amino acid residues.
J Am Chem Soc
; 137(13): 4300-3, 2015 Apr 08.
Article
en En
| MEDLINE
| ID: mdl-25794270
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Agua
/
Pliegue de Proteína
/
Aminoácidos
Idioma:
En
Revista:
J Am Chem Soc
Año:
2015
Tipo del documento:
Article
País de afiliación:
Suiza