I do not think the small molecule approach proposed by George Sheldrick is sufficient for validation of protein structures, as misrepresentation of experimental statistics/resolution is hard to detect with it, and these factors appear to play crucial role in defining the fate of many hot structures.
The bad statistics hurts publication more than mistakes in a model, and improving the experiment is often too hard. "I know my structure is right. Why should I spend another year growing better crystals only to make the statistics look right?" - sounds as a strong argument for a desperate researcher. Making up an artificial data set overkills the task. There are easier and "less amoral" ways such as rejection of outliers and incorrect assignment of the Rfree test set. Ironically, an undereducated crystallographer may not recognize wrongdoing in such data treatment, which makes it even more likely to occur. Do I sound paranoid? And please do not suggest that I have shared personal experiences. Alex Aleshin On Sat, 18 Aug 2007, George M. Sheldrick wrote: > There are good reasons for preserving frames, but most of all for the > crystals that appeared to diffract but did not lead to a successful > structure solution, publication, and PDB deposition. Maybe in the future > there will be improved data processing software (for example to integrate > non-merohedral twins) that will enable good structures to be obtained from > such data. At the moment most such data is thrown away. However, forcing > everyone to deposit their frames each time they deposit a structure with > the PDB would be a thorough nuisance and major logistic hassle. > > It is also a complete illusion to believe that the reviewers for Nature > etc. would process or even look at frames, even if they could download > them with the manuscript. > > For small molecules, many journals require an 'ORTEP plot' to be submitted > with the paper. As older readers who have experienced Dick Harlow's 'ORTEP > of the year' competition at ACA Meetings will remember, even a viewer > with little experience of small-molecule crystallography can see from the > ORTEP plot within seconds if something is seriously wrong, and many > non-crystallographic referees for e.g. the journal Inorganic Chemistry > can even make a good guess as to what is wrong (e.g wrong element assigned > to an atom). It would be nice if we could find something similar for > macromolecules that the author would have to submit with the paper. One > immediate bonus is that the authors would look at it carefully > themselves before submitting, which could lead to an improvement of the > quality of structures being submitted. My suggestion is that the wwPDB > might provide say a one-page diagnostic summary when they allocate each > PDB ID that could be used for this purpose. > > A good first pass at this would be the output that the MolProbity server > http://molprobity.biochem.duke.edu/ sends when is given a PDB file. It > starts with a few lines of summary in which bad things are marked red > and the structure is assigned to a pecentile: a percentile of 6% means > that 93% of the sturcture in the PDB with a similar resolution are > 'better' and 5% are 'worse'. This summary can be understood with very > little crystallographic background and a similar summary can > of course be produced for NMR structures. The summary is followed by > diagnostics for each residue, normally if the summary looks good it > would not be necessary for the editor or referee to look at the rest. > > Although this server was intended to help us to improve our structures > rather than detect manipulated or fabricated data, I asked it for a > report on 2HR0 to see what it would do (probably many other people were > trying to do exactly the same, the server was slower than usual). > Although the structure got poor marks on most tests, MolProbity > generously assigned it overall to the 6th pecentile, I suppose that > this is about par for structures submitted to Nature (!). However there > was one feature that was unlike anything I have ever seen before > although I have fed the MolProbity server with some pretty ropey PDB > files in the past: EVERY residue, including EVERY WATER molecule, made > either at least one bad contact or was a Ramachandran outlier or was a > rotamer outlier (or more than one of these). This surely would ring > all the alarm bells! > > So I would suggest that the wwPDB could coordinate, with the help of the > validation experts, software to produce a short summary report that > would be automatically provided in the same email that allocates the PDB > ID. This email could make the strong recommendation that the report file > be submitted with the publication, and maybe in the fullness of time > even the Editors of high profile journals would require this report for > the referees (or even read it themselves!). To gain acceptance for such > a procedure the report would have to be short and comprehensible to > non-crystallographers; the MolProbity summary is an excellent first > pass in this respect, but (partially with a view to detecting > manipulation of the data) a couple of tests could be added based on the > data statistics as reported in the PDB file or even better the > reflection data if submitted). Most of the necessary software already > exists, much of it produced by regular readers of this bb, it just needs > to be adapted so that the results can be digested by referees and > editors with little or no crystallographic experience. And most important, > a PDB ID should always be released only in combination with such a > summary. > > George > > Prof. George M. Sheldrick FRS > Dept. Structural Chemistry, > University of Goettingen, > Tammannstr. 4, > D37077 Goettingen, Germany > Tel. +49-551-39-3021 or -3068 > Fax. +49-551-39-2582 >
