期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2013
卷号：110
期号：42
页码：16826-16831
DOI：10.1073/pnas.1315525110
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：A method that makes use of information provided by the combination of 13C and 13C{beta} chemical shifts, computed at the density functional level of theory, enables one to (i) validate, at the residue level, conformations of proteins and detect backbone or side-chain flaws by taking into account an ensemble average of chemical shifts over all of the conformations used to represent a protein, with a sensitivity of [~]90%; and (ii) provide a set of ({chi}1/{chi}2) torsional angles that leads to optimal agreement between the observed and computed 13C and 13C{beta} chemical shifts. The method has been incorporated into the CheShift-2 protein validation Web server. To test the reliability of the provided set of ({chi}1/{chi}2) torsional angles, the side chains of all reported conformations of five NMR-determined protein models were refined by a simple routine, without using NOE-based distance restraints. The refinement of each of these five proteins leads to optimal agreement between the observed and computed 13C and 13C{beta} chemical shifts for [~]94% of the flaws, on average, without introducing a significantly large number of violations of the NOE-based distance restraints for a distance range [≤] 0.5 [A], in which the largest number of distance violations occurs. The results of this work suggest that use of the provided set of ({chi}1/{chi}2) torsional angles together with other observables, such as NOEs, should lead to a fast and accurate refinement of the side-chain conformations of protein models.
