skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Ensemble Refinement of Protein Crystal Structures: Validation and Application

Abstract

X-ray crystallography typically uses a single set of coordinates and B factors to describe macromolecular conformations. Refinement of multiple copies of the entire structure has been previously used in specific cases as an alternative means of representing structural flexibility. Here, we systematically validate this method by using simulated diffraction data, and we find that ensemble refinement produces better representations of the distributions of atomic positions in the simulated structures than single-conformer refinements. Comparison of principal components calculated from the refined ensembles and simulations shows that concerted motions are captured locally, but that correlations dissipate over long distances. Ensemble refinement is also used on 50 experimental structures of varying resolution and leads to decreases in Rfree values, implying that improvements in the representation of flexibility observed for the simulated structures may apply to real structures. These gains are essentially independent of resolution or data-to-parameter ratio, suggesting that even structures at moderate resolution can benefit from ensemble refinement.

Authors:
; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
959564
Report Number(s):
BNL-82550-2009-JA
Journal ID: ISSN 0092-8674; CELLB5; TRN: US201016%%708
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cell; Journal Volume: 15
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; DIFFRACTION; FLEXIBILITY; PROTEINS; RESOLUTION; VALIDATION; national synchrotron light source

Citation Formats

Levin,E., Kondrashov, D., Wesenberg, G., and Philips, Jr., G. Ensemble Refinement of Protein Crystal Structures: Validation and Application. United States: N. p., 2007. Web. doi:10.1016/j.str.2007.06.019.
Levin,E., Kondrashov, D., Wesenberg, G., & Philips, Jr., G. Ensemble Refinement of Protein Crystal Structures: Validation and Application. United States. doi:10.1016/j.str.2007.06.019.
Levin,E., Kondrashov, D., Wesenberg, G., and Philips, Jr., G. Mon . "Ensemble Refinement of Protein Crystal Structures: Validation and Application". United States. doi:10.1016/j.str.2007.06.019.
@article{osti_959564,
title = {Ensemble Refinement of Protein Crystal Structures: Validation and Application},
author = {Levin,E. and Kondrashov, D. and Wesenberg, G. and Philips, Jr., G.},
abstractNote = {X-ray crystallography typically uses a single set of coordinates and B factors to describe macromolecular conformations. Refinement of multiple copies of the entire structure has been previously used in specific cases as an alternative means of representing structural flexibility. Here, we systematically validate this method by using simulated diffraction data, and we find that ensemble refinement produces better representations of the distributions of atomic positions in the simulated structures than single-conformer refinements. Comparison of principal components calculated from the refined ensembles and simulations shows that concerted motions are captured locally, but that correlations dissipate over long distances. Ensemble refinement is also used on 50 experimental structures of varying resolution and leads to decreases in Rfree values, implying that improvements in the representation of flexibility observed for the simulated structures may apply to real structures. These gains are essentially independent of resolution or data-to-parameter ratio, suggesting that even structures at moderate resolution can benefit from ensemble refinement.},
doi = {10.1016/j.str.2007.06.019},
journal = {Cell},
number = ,
volume = 15,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}