Artículo
Use of 13Ca chemical shifts for accurate determination of beta-Sheet structures in solution
Fecha de publicación:
02/2008
Editorial:
National Academy of Sciences
Revista:
Proceedings of the National Academy of Sciences of The United States of America
ISSN:
0027-8424
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
A physics-based method, aimed at determining protein structures by using NOE-derived distance constraints together with observed and computed 13Cα chemical shifts, is applied to determine the structure of a 20-residue all-β peptide (BS2). The approach makes use of 13Cα chemical shifts, computed at the density functional level of theory, to derive backbone and side-chain torsional constraints for all of the amino acid residues, without making use of information about residue occupancy in any region of the Ramachandran map. In addition, the torsional constraints are derived dynamically—i.e., they are redefined at each step of the algorithm. It is shown that, starting from randomly generated conformations, the final protein models are more accurate than existing NMR-derived models of the peptide, in terms of the agreement between predicted and observed 13Cβ chemical shifts, and some stereochemical quality indicators. The accumulated evidence indicates that, for a highly flexible BS2 peptide in solution, it may not be possible to determine a single structure (or a small set of structures) that would satisfy all of the constraints exactly and simultaneously because the observed NOEs and 13Cα chemical shifts correspond to a dynamic ensemble of conformations. Analysis of the structural flexibility, carried out by molecular dynamics simulations in explicit water, revealed that the whole peptide can be characterized as having liquid-like behavior, according to the Lindemann criterion. In summary, a β-sheet structure of a highly flexible peptide in solution can be determined by a quantum-chemical-based procedure.
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IMASL)
Articulos de INST. DE MATEMATICA APLICADA DE SAN LUIS
Articulos de INST. DE MATEMATICA APLICADA DE SAN LUIS
Citación
Vila, Jorge Alberto; Arnautova, Yelena A.; Scheraga, Harold A.; Use of 13Ca chemical shifts for accurate determination of beta-Sheet structures in solution; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 105; 6; 2-2008; 1891-1896
Compartir
Altmétricas