IMASL   20939
INSTITUTO DE MATEMATICA APLICADA DE SAN LUIS "PROF. EZIO MARCHI"
Unidad Ejecutora - UE
artículos
Título:
Physics-based method to validate and repair flaws in protein structures
Autor/es:
MARTIN, OSVALDO A.; ARNAUTOVA, YELENA A.; ICAZATTI, ALEJANDRO; SCHERAGA, HAROLD A.; VILA, JORGE A.
Revista:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Editorial:
NATL ACAD SCIENCES
Referencias:
Lugar: Washington DC, USA; Año: 2013 vol. 110 p. 16826 - 16831
ISSN:
0027-8424
Resumen:
A method that makes use of information provided by thecombination of 13Cα and 13Cβ chemical shifts, computed at thedensity functional level of theory, enables one to (i) validate, atthe residue level, conformations of proteins and detect backboneor side-chain flaws by taking into account an ensemble average ofchemical shifts over all of the conformations used to representa protein, with a sensitivity of ∼90%; and (ii) provide a set of(χ1/χ2) torsional angles that leads to optimal agreement betweenthe observed and computed 13Cα and 13Cβ chemical shifts. Themethod has been incorporated into the CheShift-2 protein valida-tion Web server. To test the reliability of the provided set of (χ1/χ2) torsional angles, the side chains of all reported conformationsof five NMR-determined protein models were refined by a simpleroutine, without using NOE-based distance restraints. The refine-ment of each of these five proteins leads to optimal agreementbetween the observed and computed 13Cα and 13Cβ chemical shiftsfor ∼94% of the flaws, on average, without introducing a signifi-cantly large number of violations of the NOE-based distancerestraints for a distance range ≤ 0.5 Å, in which the largest numberof distance violations occurs. The results of this work suggest thatuse of the provided set of (χ1/χ2) torsional angles together withother observables, such as NOEs, should lead to a fast and accuraterefinement of the side-chain conformations of protein models.