Origin and Orientation
A tragic week in the crystallographic community (see: 449 Citations maybe Effected by Retracted Structures). The Birmingham News article mentions researchers finding a preponderance of evidence that the structures were incorrect. I do not have any direct proof that the crystallographic data were falsified or fabricated, but let’s take a walk.
How could only one person publish these structures without others knowing?
A lab produces crystals, collects data, but unfortunately is unable to process the data. The grad student is frustrated, the post-doc can’t figure it out and so the data is handed to the PI. The PI works on the data set in their office (over the weekend, at home, etc…) and emerges successful! The paper is written and only one person knows exactly how the structure was solved.
How could the data have been fabricated?
Let us take a look at the one structure that has already been removed from PDB: 1BEF.
The data could have been back generated from a desired protein structure using a tool like mlfsom.
However, I believe there is a better explanation.
Another method to fake the data would be to perform an isomorphous replacement using a related protein. A number of residues would be different and with some help from a homology server you could tweek the structure.
The problem is that reviewers could be experts on those structures and would notice small anomalies. In addition, the protein would need to fold ‘perfectly’ in order to be used for isomorphous replacement so that proper crystal packing is maintained.
To avoid this scenario you could find a structure that is crystallographically unrelated (different space group and unit cell) to the protein of interest and use it as a template.
In order for this hypothesis to be supported, we would need to find the unrelated structure in the PDB.
Needle in a hay stack type of problem.
To save you some time, we are going to tell you the structure used: 1NS3
The figure at right shows 1BEF in light green and 1NS3 in aqua green:
Here is the PyMol script for those that like to play along at home:
select 1ns3_A, 1ns3 and chain A+C
show ribbon, 1bef
show ribbon, 1ns3_A
The following is the crystal information from the PDB headers:
CRYST1 48.800 62.400 39.600 90.00 96.70 90.00 P 1 21 1
CRYST1 96.960 96.960 167.100 90.00 90.00 120.00 P 63 2 2
1NS3 was used as the starting model and with the addition of some water and noise, bingo.
The unit cell and space groups are totally different and yet the two structures have nearly an identical origin and orientation.
What are the chances of two crystallographically unrelated structures having the same origin and orientation?
The structures still don’t look close enough for your liking? Take 1BEF and put it into a homology server like MODELLER then compare.
Follow up: Covering your Tracks