Hi Gino, Tom and Randy,

I would rather argue for a future  “specialized” phenix low res molecular replacement application/wizard  than for simple conversion to throw an EM map into a standard MR procedure. In my experience, MR with EM models is significantly more complex than with a molecular model for several reasons. For example,

- the EM maps may suffer from scaling errors which can have a severe impact on packing function scores  and downstream averaging procedures, so an automatic “scale grid search” would be really useful.

- EM maps sometimes are affected by accumulation of density along axes of symmetry of particles  which can severely bias the outcome. Sometimes grid searches for the origin of symmetry combined with initial low-res averaging steps are helpful.

- Maps without an associated molecular model are difficult to break into conformationally rigid parts. Although many EM structures are derived on the basis of conformational classification or sorting, this information is not usually presented in a useful way in publications or database depositions.

- Negative stain (cryo) EM maps are particular prone to conformation distortions due to staining artifacts.

- For particles with strongly preferred orientations on the EM grid, the maps may have some special features

- …

A preferred application for (low-res) MR from EM maps ( or also SAXS data ???)  would ideally be able to solve some of these problems. A plain density to structure factor conversion as an entry to standard MR can already easily be done manually.  But if it’s done automatically without overcoming the above problems, many research will once try “automated MR from EM” through wizard X. If this ends unsuccessfully, they may believe their problem could simply not be solved and feel discouraged from investing a little more time and finally miss a chance to solve their problems.

Cheers,

                Timm

Dr. Timm Maier

ETH Zurich

Institute of Molecular Biology and Biophysics

HPK H 5

Schafmattstr. 20

8093 Zurich

SWITZERLAND

e-mail: [email protected]

phone ++41 44 633 3148