You are the one who should judge your statement, but it looks plausible to me.

 

Now that I think of it: why do we need referees if every scientist should judge their own hypothesis? Publication will be a lot faster if we no longer need to heed the remarks of some grumpy referees and send in revision after revision. Also the number of publications will increase significantly if every scientist is allowed to judge their own papers!

 

HS

---

From: Jacob Keller [mailto:[log in to unmask]]
Sent: Tuesday, March 12, 2013 4:14 PM
To: Schreuder, Herman R&D/DE
Cc: [log in to unmask]
Subject: Re: [ccp4bb] validating ligand density

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.  

I guess there is a good likelihood that you are right, but who am I to judge?

JPK

 

 

Herman

---

From: CCP4 bulletin board [mailto:[log in to unmask]] On Behalf Of Jacob Keller
Sent: Tuesday, March 12, 2013 3:44 PM

To: [log in to unmask]
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:[log in to unmask]] On Behalf Of Robbie
Joosten
Sent: Tuesday, March 12, 2013 10:03 AM
To: [log in to unmask]
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:[log in to unmask]] On Behalf Of
> R.Srinivasan
> Sent: Monday, March 11, 2013 23:03
> To: [log in to unmask]
> 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: [log in to unmask]

*******************************************

--
*******************************************

Jacob Pearson Keller, PhD

Looger Lab/HHMI Janelia Farms Research Campus

19700 Helix Dr, Ashburn, VA 20147

email: [log in to unmask]

*******************************************