SciTheory has a post, complete with links to the relevant articles in Science, etc., on a recent batch of trouble in structural biology. Geoffrey Chang and his group at Scripps have been working on the structures of transporter proteins, which sit in the cell membrane and actively move nonpermeable molecules in and out. There are a heap of these things, since (as any medicinal chemist will tell you) a lot of reasonable-looking molecules just won't get into cells without help. It's even tougher at a physiological level, because (from a chemist's perspective) many of the things that need to be shuttled around aren't very reasonable-looking at all - they're too small and polar or too large and greasy.
Many of these transportersm especially in bacteria, fall into a large group known as the ABC transporters, which have an ATP binding site in them for fuel. (For the non-scientists in the audience, ATP is the molecule used for energy storage in everything living on Earth. Thinking of an ATP-binding site as a NiCad battery pack gets you remarkably close to the real situation). Chang solved the structure of one of these, the bacterial protein MsbA, by X-ray crystallography back in 2001, and it was quite an accomplishment. Getting good X-ray diffraction data on proteins which spend their lives stuck in the cell membrane is rather a black art.
How dark an art is now apparent - here's the original paper's abstract in PubMed, but if you look just above the abstract, you'll see a retraction notice, and it's not alone. Five papers on various structures have been withdrawn. As SciTheory says, anyone who doubted the original MsbA structure had some real food for thought last year when another bacterial transporter was solved at the ETH in Zurich. These two should have looked more similar than they did, to most ways of thinking, but they were quite divergent.
And now we know why. Chang's group was done in by some homebrew software which swapped two columns of data. In a structure this large and complicated, you can have such disruptive things happen and still be able to settle down on a final protein picture - it's just that it'll be completely wrong. And so it was. The same software seems to have undermined the other determinations, too.
This is important (as well as sad and painful) on several levels. For one thing, transporters are essential to understanding resistance to antibiotics and cancer therapies, and they're vital parts of a lot of poorly understood processes in normal cells. We're not going to be able to get a handle on the often-inscrutable distribution of drug candidates in living systems until we know more about these proteins, but now some of what we thought we knew has evaporated on us.
Another point that people shouldn't miss is the trouble with relying too much on computational methods. There's really no alternative to them in protein crystallography, of course, but there always has to be a final "Does that make sense?" test. The difficulty is that many perfectly valid protein structures show up with odd and surprising features. Alternately, it's unnerving that the data for these things can be so thoroughly hosed and still give you a valid-looking structure, but that just serves to underline how careful you have to be.
And we're talking about X-ray data, which (done properly) is considered to be pretty solid stuff. So what does this say about basing research programs on the higher levels of abstraction found in molecular modeling and docking progams?