Daniel Russel wrote:
> With Keren, we ran into problem caused the fact that em restraints go to
> 1 as they are increasingly violated while hard sphere restraints go to
> larger numbers (and are dependent on the number of particles). The
> result was that the em restraint would get more or less ignored by the
> optimizer unless a large scaling factor was added to EM.
This is just basic physics - most restraints are extensive, in that they
scale with the system size (e.g. excluded volume, stereochemistry). Any
CC-like restraint is intensive, and doesn't scale with system size.
Obviously that doesn't work when you combine the two.
For EM we solved this years ago with a scaling factor. Ideally the scale
would simply be N^2 where N is the number of particles in the system.
I don't much like the idea of scaling "regular" restraints by the number
of atoms or similar, since that would break pretty much everything else
where the assumption is made that the sum of the restraints is a score
that can be safely minimized (this assumes that the score does increase
as you add atoms, and restraints on multiple atoms should have more
weight than those on just pairs). But for intensive restraints like EM
it would certainly make sense to automatically weight them in a sensible
way so optimization works correctly.
"It is a capital mistake to theorize before one has data."
- Sir Arthur Conan Doyle