[3dem] pdb for near-atomic resolution EM maps

Masahide Kikkawa mkikkawa at m.u-tokyo.ac.jp
Tue Dec 2 00:09:02 PST 2014

Hi Irina,

> I would like to deposit a near-atomic resolution map (4.3A) and the corresponding atomic model to the respective databases. Given recent discussions about overinterpretation of the data I am wondering what would be the best way to proceed.
> Indeed, some bulky side chains are clearly visible and could be placed with confidence, in particular in certain regions of the map (according to ResMap local resolution ranges from 3.5A to above 6A), but most of them not.

If you look into the PDB database, there are plenty of "atomic structures" build based on 4-6A resolution X-ray crystallographic data. Since phase information derived from X-ray is not as reliable as those from cryo-EM at this resolution range, those atomic models often turned out to be wrong. On the other hand, we (electron microscopists) should try to extract as much data as possible and try to interpret the density map, with caution.

Therefore, in my opinion, it is user's responsibility to check the validity of the "model" deposited to PDB.
To make this user's validation easier, a combination of EM density map (EMDB) and corresponding atomic coordinate (PDB) should be deposited. In the future, it would be desirable to develop a cryo-EM version of  Rfree (already exists?).

> And even the criteria of "visibility" and "confidence" are subjective. The protein complex is of big pharmaceutical interest and I suppose that if the complete pdb with all the side chains is deposited, it may be downloaded and used for example for drug design, as a kind of "absolute truth", which might be dangerous. However, deposit only the c-alpha is probably too restrictive. Another option would be to deposit only the side chains we are "sure about", but again, it's subjective, and anyway we can only be "sure" at the given resoluition. So what would be the most honest and unbiased way to share these results with the scientific community, in particular with biologists who are not necessarily aware of the overinterpretation/overfitting/validation/etc issues in our field but who use our results to design their experiments?

Masahide Kikkawa, M.D., Ph. D.
Department of Cell Biology & Anatomy
Graduate School of Medicine
The University of Tokyo
tel: +81-3-5841-3338
fax: +81-3-5841-3339

More information about the 3dem mailing list