Dear Jacob,
You are overinterpreting, the statement is about judging, not proving a
hypothesis. I am sure Mr. Edwards judged his statement to be ok. ;-)
Herman
________________________________
From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On
Behalf Of Jacob Keller
Sent: Tuesday, March 12, 2013 3:44 PM
To: CCP4BB@JISCMAIL.AC.UK
Subject: Re: [ccp4bb] validating ligand density
One final quote that is not in the twilight paper
summarizes it nicely:
"The scientist must be the judge of his own hypotheses,
not the
statistician."
A.F.W. Edwards (1992) in Likelihood - An account of the
statistical concept
of likelihood and its application to scientific
inference , p. 34.
There must be a lot of thinking behind this statement--while it
seems plausible, it seems far from proven prima facie. Also, it assumes
that the scientist is not a statistician.
Jacob
Btw, the book is good reading.
Best, BR
-----Original Message-----
From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK]
On Behalf Of Robbie
Joosten
Sent: Tuesday, March 12, 2013 10:03 AM
To: CCP4BB@JISCMAIL.AC.UK
Subject: Re: [ccp4bb] validating ligand density
Dear Srinivasan,
Although the Twilight program can only look at deposited
PDB entries, the
tips about ligand validation in the paper are very
useful. I suggest you
start from there.
You can use EDSTATS in CCP4 to get real-space validation
scores. Also look
at the difference map metrics it gives (and the maps
themselves of course),
they will tell you whether you misidentified your
ligand. Occupancy
refinement in Refmac can also help you: if the occupancy
drops a lot
something is wrong. That can be partial binding (not
that much of a problem)
or worse, a ligand that isn't there. By the way, I've
been playing with
that recently and some ligands/hetero compounds in the
PDB were so
incredibly 'not there' that Refmac would crash (that bug
seems to be fixed
in the latest version).
HTH,
Robbie
> -----Original Message-----
> From: CCP4 bulletin board
[mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of
> R.Srinivasan
> Sent: Monday, March 11, 2013 23:03
> To: CCP4BB@JISCMAIL.AC.UK
> Subject: [ccp4bb] validating ligand density
>
> Hello all,
>
> We co-crystallized an inactive variant of
our enzyme in
> the
presence of
> substrate and have determined the structure at 1.85A.
>
> Now, we want to validate the fitting of
the ligand into
> the
electron
> density. We tried validating using the difference map
(2Fo-Fc) after
refining
> the structure without the ligand. But, it is still a
bit inconclusive
> if
the density
> fits the ligand.
>
> It would be very kind to know if there are
tools for
validating this
> electron density. We were excited about twilight but
turns out it can
> only
be
> used with deposited structure.
>
>
> We will appreciate your help and
suggestions.
>
>
> Many thanks,
> Srinivasan
--
*******************************************
Jacob Pearson Keller, PhD
Looger Lab/HHMI Janelia Farms Research Campus
19700 Helix Dr, Ashburn, VA 20147
email: kell...@janelia.hhmi.org
*******************************************
