Homology-based hydrogen bond information improves crystallographic structures in the PDB

Abstract

Crystallographic structure models in the Protein Data Bank (PDB) are optimized against the crystal diffraction data and geometrical restraints. This process of crystallographic refinement typically ignored hydrogen bond (H-bond) distances as a source of information. However, H-bond restraints can improve structures, especially at low resolution where diffraction data are limited. To improve low-resolution structure refinement, we present methods for deriving H-bond information either globally from well-refined high-resolution structures from the PDB-REDO databank, or specifically from on-the-fly constructed sets of homologous high-resolution structures. Refinement incorporating HOmology DErived Restraints (HODER), improves geometrical quality and the fit to the diffraction data for many low-resolution structures. Using approximately 60 years of CPU-time in massively parallel computing, we constructed a new instance of the PDB-REDO databank, a novel resource to help biologists gain insight on protein families or on specific structures, as we demonstrate with examples.