Abstract
Accurate crystal structures of macromolecules are of high importance in the biological and biomedical fields. Models of crystal structures in the Protein Data Bank (PDB) are in general of very high quality as deposited. However, methods for obtaining the best model of a macromolecular structure from a given set of experimental X-ray data continue to progress at a rapid pace, making it possible to improve most PDB entries after their deposition by re-analyzing the original deposited data with more recent software. This possibility represents a very significant departure from the situation that prevailed when the PDB was created, when it was envisioned as a cumulative repository of static contents. A radical paradigm shift for the PDB is therefore proposed, away from the static archive model towards a much more dynamic body of continuously improving results in symbiosis with continuously improving methods and software. These simultaneous improvements in methods and final results are made possible by the current deposition of processed crystallographic data (structure-factor amplitudes) and will be supported further by the deposition of raw data (diffraction images). It is argued that it is both desirable and feasible to carry out small-scale and large-scale efforts to make this paradigm shift a reality. Small-scale efforts would focus on optimizing structures that are of interest to specific investigators. Large-scale efforts would undertake a systematic re-optimization of all of the structures in the PDB, or alternatively the redetermination of groups of structures that are either related to or focused on specific questions. All of the resulting structures should be made generally available, along with the precursor entries, with various views of the structures being made available depending on the types of questions that users are interested in answering.
Highlights
Several technical advances have reduced the prevalence of model bias, but its ever-present risk needs to be borne in mind at all times. These errors and limitations decrease markedly if the X-ray data extend to high resolution, while they can be very severe for crystal structures determined with X-ray data extending to only low resolution (e.g. 3.5 Aor poorer; see, for example, Hunt & Deisenhofer, 2003)
We suggest that despite the technical challenges that the task is bound to present, the structural biology community can and should undertake systematically to improve the tens of thousands of models in the Protein Data Bank (PDB) that represent macromolecular crystal structures and make them available within the PDB itself
We propose that the PDB should maintain both original interpretations and reinterpretations of macromolecular structural data as integral and widely accessible elements of its repository
Summary
The three-dimensional structures of biological macromolecules such as proteins, DNA and RNA are of high importance in many areas of biology and biotechnology. The typical procedure followed in the determination of a crystal structure is for a single person or group to collect X-ray diffraction data, obtain information on phases, create electron-density maps, interpret these maps in terms of an atomic model and refine the model to optimize its agreement with the diffraction data while maintaining conformity with the relevant a priori knowledge of macromolecular geometry. Once this procedure has been carried out, the resulting model and X-ray diffraction intensities are deposited as an ‘entry’ in the PDB and become available to anyone who wishes to use them. This remediation was primarily aimed at achieving consistency in nomenclature and formatting of the data, some errors were corrected as well
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