Yes, B factors are indeed a super-absorbent sponge for model bias. Best
to re-set those before re-refinement. But you should also do something
with the coordinates, and probably the occupancies too.
My jiffy to add to Graeme's list of options is this script:
http://bl831.als.lbl.gov/~jamesh/scripts/jigglepdb.awk
It has a variety of options, including separate rms shifts for
coordinates, B factors and occupancies (shift=, Bshift=, and Oshift=),
and a special option called "shift=byB" that moves coordinates in
accordance to the atom's B factor. The distribution of the shifts can
be Gaussian (default), Lorentzian or uniform sphere. The latter is
useful if you want to avoid very large shifts (see below). By default,
one conformer (i.e. A, B, C) is randomly given an occupancy of "1" for
all residues and all the other conformers are given zero. This is an
attempt to simulate the cell-to-cell variation of the structure, which
can only have one conformer at a time. If you specify "keepocc=1" this
behavior gets turned off. Any non-zero "Oshift" will add random noise
to all occupancies.
I'm sure all this functionality would be easy to re-create using CCTBX
as well.
I've actually played around with "jiggling" pdb files a fair bit. Turns
out that in order to remove "bias" completely you need to kick the atoms
by an rms distance comparable to the relevant resolution. That is, 1.5 A
for 1.5 A spots, but also 6 A if you want to un-bias 6 A spots. This
tends to be outside the radius of convergence of most refinement
programs. In fact, kicking atoms by as little as 0.5 A can often result
in some side chains falling into alternate rotamers and the like.
Waters can also fall out of place and drift into nearby pockets of
liberated density. You can do a "cleanup" after re-refinement to
correct for such gross errors. Looking for the largest differences
between starting and re-refined models generally lights these up. But
before you "fix" these things you have to start asking questions about
what "bias" really is.
It seems a popular "bias-reduction" approach is to re-run Phaser or
other molecular replacement job, but all that really does is put your
model onto an alternative origin or asu choice. These choices are
arbitrary, of course, and crystallographically equivalent. Once you
have corrected for the origin shift using something like "reforigin" you
can see that all your Phaser run has produced is a slight rigid-body
shift relative to where you started. Hardly a bias-removal technique.
So, what is "bias"? We tend to think of "bias" the same way we think of
"twinning": as a synonym for "evil". Something to be kept out of our
models and data at all costs. But if you think about it a bit you may
realize that even having the backbone structure itself intact is a form
of "bias". As in you are "biasing" your model to resemble the overall
fold you originally assigned to the structure. You may or may not be all
that worried about this. And if you are certain that the main chain
trace is correct, then enforcing it in further analysis is not "bias",
it is "prior knowledge". I suppose knowing the difference between these
two things is what science is all about.
So, I'd say that "resetting" a structure depends on what aspect of the
structure you're trying to test. If you made a mistake in the backbone
trace, or even a rotamer assignment, then doing a 0.5A jiggle isn't
going to reset that mistake. But if your trying to test the influence
of data between 1.5 A and 1.4 A, then I'd say do a jiggle of at least
half that distance.
-James Holton
MAD Scientist
On 8/17/2017 8:40 AM, Robbie Joosten wrote:
In most cases resetting the B-factors would be enough to perturb the
model.
Cheers,
Robbie
Sent from my Windows 10 phone
*From: *Andrew Leslie <mailto:and...@mrc-lmb.cam.ac.uk>
*Sent: *17 August 2017 17:29
*To: *CCP4BB@JISCMAIL.AC.UK <mailto:CCP4BB@JISCMAIL.AC.UK>
*Subject: *Re: [ccp4bb] "reset" a structure before re-refinement
Hi Graeme,
You can do this with PDBSET, keyword NOISE
Cheers,
Andrew
> On 17 Aug 2017, at 16:17, Graeme Winter
<graeme.win...@diamond.ac.uk> wrote:
>
> Dear All,
>
> Is there a protocol out there to gently perturb atomic positions so
that re-running refinement can essentially put them back without bias
from the original refinement? In particular, if trying to perform the
Karplus and Diederichs paired refinement protocol, I do not want to
run the lower resolution refinements with the "memory" of the weak
high resolution data present... and only have the refined structure to
work from...
>
> Am using refmac5, but any pdb randomizer would hit the spot
>
> Many thanks Graeme
>
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