On 8/5/2016 4:58 PM, Murpholino Peligro wrote:
> Excellent question! So there is no way to know if the refinement
> "converged"?
> I always ploted the R values (R_free and R_work) against number of
> refinements and if the difference was very small (I guess less than 1%)
> I would say that refinement was done..i.e. it converged. So was I wrong?
Looking only at global stats can get you into serious trouble. One
atom can be moving quite a lot and not cause a blip in an over-all
number. That atom would quite likely be the metal atom in the middle of
your active site! Most refinement protocols today tend to carefully
restrain the ligand distances to your metals. One reason they do that
is because it is hard to resolve these short distances. The other
reason is that electron dense atoms tend to bounce back and forth if you
don't build the second derivatives into your optimization. If you run
more cycles of refinement you can relax the distance restraints, which
is good because those restraints might be wrong.
It used to be that refinement programs would list the atoms with the
biggest shifts in the last cycle so the user could check for
convergence. At times this practice has been dropped by some. I
haven't checked the recent versions of the big packages to see what
tools they provide.
As I said, I beat it to death to make sure. There is no harm to
running extra cycles other than time it takes.
Dale Tronrud
>
> Thanks
>
> 2016-08-05 18:17 GMT-05:00 Dale Tronrud <[log in to unmask]
> <mailto:[log in to unmask]>>:
>
>
> I have never seen a refinement "converge" in the mathematical sense.
> The optimization algorithms we use are not expected to converge until
> you have run a number of cycles greater than some multiple of the number
> of parameters in the model. No one is ever going to do this.
>
> The mistake I have seen, and what is being recommended against, is to
> just run some standard number of cycles and quit without checking to see
> if anything is still happening. Some programs have a standard of three
> "big" rounds of refinement but the R values and over all geometry might
> still be changing at the end of that, particularly early in a project.
> You certainly shouldn't stop if the major stats are in flux (either
> going up OR down).
>
> More subtly individual atoms may still be moving while the overall
> stats look stable. You should check that the largest shifts in your
> final rounds are "small". This is a fuzzy definition, but if you are
> interested in distances to a precision of 0.1 A you certainly shouldn't
> be stopping if you still have atoms moving in steps approaching that
> size.
>
> Refinement is fast these days. I tend to beat my refinements to
> death just to be sure. If the standard practice is three "big" rounds
> I'll run ten.
>
> There is no such thing as "over refinement" only "over fitting".
>
> Dale Tronrud
>
>
> On 8/5/2016 3:22 PM, Keller, Jacob wrote:
> >>>- make sure refinement is done till convergence.
> >
> >
> >
> > I have never understood and still do not understand what is meant by
> > convergence—in my experience, refinements are always incremental, with
> > various improvements here and there, but there’s never been any magic
> > moment of convergence. Is there a rigorous meaning to this term? Is it
> > just when the refinement program stops improving things?
> >
> >
> >
> > Jacob Keller
> >
> >
> >
>
>
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