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

By Nigel W. Moriarty, D. Tronrud, Paul D. Adams, Paul Karplus. 2014

37 citations recorded by the source corpus.

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 use today have been designed on the assumption that each type of bond or angle has a single ideal value that is independent of context. However, recent work has shown that the ideal values are, in fact, sensitive to local conformation, and, as a first step towards 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, 1316–1325]. 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 CDL 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, use 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 modeling accuracy.

Subfields: Materials Chemistry, Molecular Biology, Spectroscopy

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Materials Chemistry

In Molecular Biology

In Spectroscopy

Citations in the corpus

Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix (2019, methodology): “Recent additions to the restraints used in Phenix include the conformation-dependent library (Berkholz et al., 2009; Moriarty et al., 2014, 2016), which restrains the protein main chain as a function of the backbone dihedral values.”
A new default restraint library for the protein backbone in Phenix: a conformation-dependent geometry goes mainstream (2016, background): “…that conventional restraints have shortcomings, it has previously been documented that using backbone restraints that depend on the protein backbone conformation helps to address these shortcomings and improves the performance of refinements [Moriarty et al. (2014), FEBS J. 281, 4061–4071].”
An editor for the generation and customization of geometry restraints (2017, background): “…are becoming standard practice in structure refinement: single-value restraints have been shown to be inadequate for the protein backbone, and the Conformation Dependent Library (CDL; Berkholz et al., 2009) has recently been made the default in phenix.refine (Moriarty et al., 2014, 2016).”