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Title: Conformation-dependent backbone geometry restraints set a new standard for protein crystallographic refinement

Journal Article · · Federation of European Biochemical Societies (FEBS) Journal
DOI:https://doi.org/10.1111/febs.12860· OSTI ID:1172901
 [1];  [2];  [3];  [2]
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  2. Oregon State Univ., Corvallis, OR (United States). Dept. of Biochemistry and Biophysics
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States). Dept. of Bioengineering

Ideal values of bond angles and lengths used as external restraints are crucial for the successful refinement of protein crystal structures at all but the highest of resolutions. The restraints in common usage today have been designed based on the assumption that each type of bond or angle has a single ideal value independent of context. However, recent work has shown that the ideal values are, in fact, sensitive to local conformation, and as a first step toward using such information to build more accurate models, ultra-high resolution protein crystal structures have been used to derive a conformation-dependent library (CDL) of restraints for the protein backbone (Berkholz et al. 2009. Structure. 17, 1316). Here, we report the introduction of this CDL into the Phenix package and the results of test refinements of thousands of structures across a wide range of resolutions. These tests show that use of the conformation dependent library yields models that have substantially better agreement with ideal main-chain bond angles and lengths and, on average, a slightly enhanced fit to the X-ray data. No disadvantages of using the backbone CDL are apparent. In Phenix usage of the CDL can be selected by simply specifying the cdl=True option. This successful implementation paves the way for further aspects of the context-dependence of ideal geometry to be characterized and applied to improve experimental and predictive modelling accuracy.

Research Organization:
University of California, Berkeley, CA (United States)
Sponsoring Organization:
USDOE
Contributing Organization:
Phenix Industrial Consortium
Grant/Contract Number:
AC02-05CH11231; R01-GM083136; 1P01-GM063210
OSTI ID:
1172901
Journal Information:
Federation of European Biochemical Societies (FEBS) Journal, Vol. 281, Issue 18; ISSN 1742-464X
Publisher:
Federation of European Biochemical SocietiesCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 32 works
Citation information provided by
Web of Science

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Cited By (11)

MolProbity: More and better reference data for improved all-atom structure validation: PROTEIN SCIENCE.ORG journal November 2017
Accurate geometries for “Mountain pass” regions of the Ramachandran plot using quantum chemical calculations journal January 2018
Conformation-dependent restraints for polynucleotides: the sugar moiety journal December 2019
Systematic exploration of protein conformational space using a Distance Geometry approach journal August 2019
An editor for the generation and customization of geometry restraints journal February 2017
Strategies for carbohydrate model building, refinement and validation journal February 2017
Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix. text January 2019
Systematic Exploration of Protein Conformational Space Using a Distance Geometry Approach journal August 2019
Carbohydrate structure: the rocky road to automation journal June 2017
Novel halo- and thermo-tolerant Cohnella sp. A01 L-glutaminase: heterologous expression and biochemical characterization journal December 2019
Conformation-dependent restraints for polynucleotides: I. Clustering of the geometry of the phosphodiester group journal August 2016

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