期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 1, 页码 237-242出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1302823110
关键词
electron number density; refinement against perturbed input data; protein dynamics; molecular motions; Ringer
资金
- National Science Foundation
- National Science and Engineering Research Council of Canada
- National Institutes of Health [R01 48958, DP5OD009180, GM073210, GM082250, GM094625]
- US Department of Energy at Lawrence Berkeley National Laboratory [DE-AC02-05CH11231]
To increase the power of X-ray crystallography to determine not only the structures but also the motions of biomolecules, we developed methods to address two classic crystallographic problems: putting electron density maps on the absolute scale of e(-)/angstrom(3) and calculating the noise at every point in the map. We find that noise varies with position and is often six to eight times lower than thresholds currently used in model building. Analyzing the rescaled electron density maps from 485 representative proteins revealed unmodeled conformations above the estimated noise for 45% of side chains and a previously hidden, low-occupancy inhibitor of HIV capsid protein. Comparing the electron density maps in the free and nucleotide-bound structures of three human protein kinases suggested that substrate binding perturbs distinct intrinsic allosteric networks that link the active site to surfaces that recognize regulatory proteins. These results illustrate general approaches to identify and analyze alternative conformations, low-occupancy small molecules, solvent distributions, communication pathways, and protein motions.
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