A new default restraint library for the protein backbone in Phenix: a conformation-dependent geometry goes mainstream.

Nigel W Moriarty,P Andrew Karplus,Dale E Tronrud,Paul D Adams

doi:10.1107/s2059798315022408

Abstract

Chemical restraints are a fundamental part of crystallographic protein structure refinement. In response to mounting evidence 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]. It is important that these improvements be made available to all in the protein crystallography community. Toward this end, a change in the default geometry library used by Phenix is described here. Tests are presented showing that this change will not generate increased numbers of outliers during validation, or deposition in the Protein Data Bank, during the transition period in which some validation tools still use the conventional restraint libraries.

Highlights

From the above results, a formalized empirical conformation-dependent library (CDL) for trans-peptide backbone restraints was developed (Tronrud et al, 2010) and was tested in protein crystallographic refinement using the TNT (Tronrud et al, 1987) and SHELXL (Sheldrick, 2008) refinement programs
This study showed that the greater intrinsic accuracy of the CDL was already observable in structures determined at resolutions better than about 2 A, at which point the backbone bond angles began to agree better with the CDL than with the conventional library against which they were restrained
Details of the implementation of the CDL into Phenix are presented in Moriarty, Tronrud et al (2014), but here we find it useful to briefly note a few things

Summary

Introduction

A formalized empirical conformation-dependent library (CDL) for trans-peptide backbone restraints was developed (Tronrud et al, 2010) and was tested in protein crystallographic refinement using the TNT (Tronrud et al, 1987) and SHELXL (Sheldrick, 2008) refinement programs. The tests revealed the rather striking result for ultrahighresolution structures that even those that had been refined using the conventional restraint library as target values had bond angles that agreed more closely with the CDL.

Results

Conclusion