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

To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work. This is the publisher’s final pdf. The article is copyrighted by FEBS and published by John Wiley & Sons Ltd. It can be found at: http://onlinelibrary.wiley.com/journal/10.1111/%28ISSN%291742-4658.Ideal values of bond angles and lengths used as external restraints are crucial for the successful\ud refinement of protein crystal structures at all but the highest of resolutions. The restraints in\ud common usage today have been designed based on the assumption that each type of bond or\ud angle has a single ideal value independent of context. However, recent work has shown that the\ud ideal values are, in fact, sensitive to local conformation, and as a first step toward using such\ud information to build more accurate models, ultra-high resolution protein crystal structures have\ud been used to derive a conformation-dependent library (CDL) of restraints for the protein\ud backbone (Berkholz et al. 2009. Structure. 17, 1316). Here, we report the introduction of this\ud CDL into the Phenix package and the results of test refinements of thousands of structures across\ud a wide range of resolutions. These tests show that use of the conformation dependent library\ud yields models that have substantially better agreement with ideal main-chain bond angles and\ud lengths and, on average, a slightly enhanced fit to the X-ray data. No disadvantages of using the\ud backbone CDL are apparent. In Phenix usage of the CDL can be selected by simply specifying\ud the cdl=True option. This successful implementation paves the way for further aspects of the\ud context-dependence of ideal geometry to be characterized and applied to improve experimental\ud and predictive modelling accuracy