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: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 > > ******************************************* > > -- ******************************************* Jacob Pearson Keller, PhD Looger Lab/HHMI Janelia Farms Research Campus 19700 Helix Dr, Ashburn, VA 20147 email: kell...@janelia.hhmi.org *******************************************
