PDB_REDO: automated re-refinement of X-ray structure models in the PDB.

Robbie P Joosten,Marco Pagni,Ian J Tickle,Jean Salzemann,Andreas Gisel,Gert Vriend,Vincent Breton,Matthieu Reichstadt,Heinz Stockinger,Volker Flegel,Eija Korpelainen,Kimmo Mattila,Vinod Kasam,Christophe Combet,Vanessa Bloch ,Anna Luisa Costa ,R Fabbretti ,Erik Bongcam‐Rudloff ,M Diarena ,G Fettahi ,Gilbert Deléage ,Clément E Blanchet ,Asta Berglund ,Tuomas Kervinen

doi:10.1107/s0021889809008784

Abstract

Structural biology, homology modelling and rational drug design require accurate three-dimensional macromolecular coordinates. However, the coordinates in the Protein Data Bank (PDB) have not all been obtained using the latest experimental and computational methods. In this study a method is presented for automated re-refinement of existing structure models in the PDB. A large-scale benchmark with 16 807 PDB entries showed that they can be improved in terms of fit to the deposited experimental X-ray data as well as in terms of geometric quality. The re-refinement protocol uses TLS models to describe concerted atom movement. The resulting structure models are made available through the PDB_REDO databank (http://www.cmbi.ru.nl/pdb_redo/). Grid computing techniques were used to overcome the computational requirements of this endeavour.

Highlights

The availability of three-dimensional macromolecular coordinates is a prerequisite for many types of studies, such as engineering protein function and stability, understanding the molecular origin of genetic disorders, and studying intermolecular interactions
With our grid and cluster computing approach more than 90% of the total calculation was finished in only two months – this shows the clear time advantage arising from the usage of modern computing technology
We have presented and thoroughly tested a re-refinement protocol for X-ray structure models that works over a wide resolution range

Summary

Introduction

The availability of three-dimensional macromolecular coordinates is a prerequisite for many types of studies, such as engineering protein function and stability, understanding the molecular origin of genetic disorders, and studying intermolecular interactions. For some research fields the accuracy of the coordinates is more important than for others. To understand whether a single nucleotide polymorphism causes an effect that leads to a disease, one often only needs to know its location in the protein, while the precise rotameric state of the amino acid side chain is of lesser importance. On the other hand, even small inaccuracies in atomic coordinates can have detrimental effects on predictions of intermolecular contacts. Many methods in macromolecular structural bioinformatics are parameterized on the basis of known protein structures. Macromolecular crystallography methods have improved a lot

Methods

Results

Conclusion