Re: [ccp4bb] open old job list under a project in a newly installed ccp4

[Robbie Joosten]

Hi Raj,

 

You can just add the old project directory as a new project in your new 
installation.

 

Cheers,

Robbie

 

From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Raja Dey
Sent: Tuesday, October 11, 2016 21:53
To: CCP4BB@JISCMAIL.AC.UK
Subject: [ccp4bb] open old job list under a project in a newly installed ccp4

 

Dear Members,

How can I open old job list under an old project in a newly installed ccp4?



Regards,

Raj

[ccp4bb] open old job list under a project in a newly installed ccp4

[Raja Dey]

Dear Members,
How can I open old job list under an old project in a newly installed ccp4?

Regards,
Raj

[ccp4bb] Beamtime @ SLS

[Meitian Wang]

===
SYNCHROTRON BEAM TIME FOR MACROMOLECULAR CRYSTALLOGRAPHY AT SLS
===

Proposal application deadline: Saturday, October 15, 2016

Periods:
January 1, 2017 - June 30, 2017 (Normal / Test proposals)
January 1, 2017 - December 31, 2018 (Long-term proposals)

Proposal submission:
http://www.psi.ch/sls/px-beamlines-call-for-proposals 


What's New (http://www.psi.ch/sls/pxi/pxi ) ?
- X06SA
EIGER 16M detector (133 Hz) and 4M ROI (750 Hz)
Faster grid scan with EIGER 4M ROI (80Hz)
Automated data collection for serial crystallography 
- X06DA
Rapid access mode for experimental phasing, especially native-SAD 
(contact directly vincent.olie...@psi.ch )
- Sample changer
30 second sample exchange time
- Software
Auto data processing
Data processing tracker

Beamline characteristics and features
X06SA Beamline (http://www.psi.ch/sls/pxi/pxi )
X06DA Beamline (http://www.psi.ch/sls/pxiii/pxiii 
)
X10SA Beamline (http://www.psi.ch/sls/pxii/pxii 
)

Best regards,

The MX group at SLS

__
Meitian Wang
Swiss Light Source at Paul Scherrer Institut
CH-5232 Villigen PSI - http://www.psi.ch/sls/ 
Phone: +41 56 310 4175

[ccp4bb] Detwinning, why not?

[Gert Vriend]

Many, many years ago I worked in Rossmann's lab. Some colleagues were 
detwinning a structure. Whatever they tried, the twin ration went from 
something near 50-50 to something near 95-5 without any improvement. I 
wrote software that would look at reflection files in search of 
systematic absences (don't laugh these were the days before the 
internet; we still used puched cards) and corrected their spacegroup 
from P23 to P213 (or something similat; at least a sub-1 was added). 
That saved that day. So my only X-ray experience gave one example where 
detwinning doesn't work: wrong spacegroup.


Gert

[ccp4bb] POSTDOCTORAL POSITIONS ION CHANNEL STRUCTURAL BIOLOGY, MINOR LAB UCSF

[Minor, Daniel L]

UNIVERSITY OF CALIFORNIA SAN FRANCISCO (UCSF)
POSTDOCTORAL POSITIONS, MINOR LAB
Structural studies of ion channels

Postdoctoral positions in Ion Channel Structural Biology are available 
immediately for highly motivated individuals with a strong interest in 
crystallographic and cryo-electron microscopy studies of ion channels the lab 
of Prof. Dan Minor at the University of California, San Francisco (UCSF).  The 
Minor Lab merges structural, biochemical, genetic, and electrophysiological 
methods to dissect the mechanism of complex protein machines involved in 
electrical signaling. More information is available at the lab website: 
http://www.cvri.ucsf.edu/~dminor/

The posts offer ideal opportunities for experienced crystallographers 
interested in continuing structural studies, but who would like to complement 
his or her expertise with other, diverse tools for understanding membrane 
protein function and mechanism.  Projects focus on determining the structures 
of a variety of full-length membrane protein and complexes by both 
crystallographic and single particle cryo-electron microscopy approaches.. The 
fellows will benefit from both the outstanding environment in the lab and the 
highly collaborative UCSF community. The lab has extensive crystallographic 
resources, including (as part of the UCSF crystallography group) two R-axis IV 
systems and regular access to synchrotron beamline 8.3.1 at the nearby Advanced 
Light Source (ALS) in Berkeley as well as access to state-of-the-art electron 
microscopes and the latest generation of K2 Summit direct electron detectors.

Candidates should have (or expect) an Ph.D. or M.D. and should have experience 
in protein biochemistry and structure determination by crystallographic or 
cryo-electronmicroscopy methods.

Interested individuals should send a current CV to Prof. Daniel Minor at 
daniel.mi...@ucsf.edu



Dan Minor, Ph.D.
Professor
Cardiovascular Research Institute
Departments of Biochemistry & Biophysics,
and Cellular & Molecular Pharmacology
California Institute for Quantitative Biomedical Research
Kavli Institute for Fundamental Neuroscience
University of California, San Francisco


FEDEX/UPS address:

Cardiovascular Research Institute
Box 3122
University of California San Francisco
555 Mission Bay Blvd. South. Rm 452Z
San Francisco, CA 94158-9001

Email: daniel.mi...@ucsf.edu
Phone: 415-514-2551
Fax: 415-476-8173
Web: http://www.cvri.ucsf.edu/~dminor

Re: [ccp4bb] Why Does Detwinning Not Work?

[Keller, Jacob]

Let me clarify: twin *refinement* is definitely the way to go. Detwinning data 
*prior* to structure solution, however, always seems to worsen things, whether 
for MR or experimental phasing. But it is hard to imagine how detwinning makes 
data worse than not, if we’ve modelled twinning appropriately; any degree of 
detwinning should bring intensities closer to their true values, making 
structure solutions better. Or at least not *worse*!

I would therefore suggest that there is something about our twinning model that 
does not fit the data. Maybe:

A. Twinned data generally have variable twin fractions across the datasets due 
to changes in illuminated volumes. Since we detwin between reflections measured 
at different rotation angles, the math would be wrong.

B. Diffraction from different twin domains combines not only additively as 
intensities but also vectorially as structure factors. This would be more 
pronounced as twin domains get smaller in size.

C. Something else?

It is just so strange to me that twinning, which is in principle something 
fully understood, should ever prevent structure solution. Even a 50% twin 
should be no worse than halving the number of observations, right?

JPK


From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Bernhard 
Rupp
Sent: Tuesday, October 11, 2016 8:09 AM
To: CCP4BB@JISCMAIL.AC.UK
Subject: Re: [ccp4bb] Why Does Detwinning Not Work?

Tom Terwilliger recently pointed me to a relevant discussion on the phenix bb:

http://phenix-online.org/pipermail/phenixbb/2013-May/019836.html​

In essence, in case of detwinning, the refinement target is not a ML target 
anymore. With
the model being used as a basis for the detwinning of Fs, the refi procedure 
becomes susceptible
to bias.

I do not know what the current state is of developing the ML target for  
refining against twinned (I, F) data is.
Garib, Randy, perhaps?

Thx, BR

From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of 
herman.schreu...@sanofi.com
Sent: Tuesday, October 11, 2016 1:23 PM
To: CCP4BB@JISCMAIL.AC.UK
Subject: [ccp4bb] AW: [ccp4bb] AW: [ccp4bb] Why Does Detwinning Not Work?

Normally, twinned refinement is the way to go. However, if the maps don’t 
become clearer and without twinned refinement the R/Rfrees are already 
0.25/0.29, there might be some other problem. Here I would be more cautious.

Herman

Von: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] Im Auftrag von Eleanor 
Dodson
Gesendet: Dienstag, 11. Oktober 2016 13:09
An: CCP4BB@JISCMAIL.AC.UK
Betreff: Re: [ccp4bb] AW: [ccp4bb] Why Does Detwinning Not Work?

Search for: "experimental phasing with detwinned data" and you will find some 
hits.
You need a low degree of twinning, and a strong sub-structure signal..
Re MR solutions - it is usually possible to solve  the structure providing you 
get the space group right, but in my experience the maps are clearer if you do 
twinned refinement. I cant see any reason not to use it?
Eleanor

On 11 October 2016 at 10:05, 
mailto:herman.schreu...@sanofi.com>> wrote:
Dear Jacob,

I agree with Chris. In my experience for MR, twinning is just like having a 
space group with one extra 2-fold (or other twin operator) so MR is indeed 
largely immune to twinning. Also the maps, calculated with uncorrected data, 
often look surprisingly good, just having a higher level of random noise.

I did not do the math, but my feeling is that the (greatly) inflated 
measurement errors (exploding as you mention near a twin fraction of 0.5) make 
direct phasing methods, that are often at the very limit of useable signal to 
noise ratio, fail after detwinning.  Also, an incorrectly estimated twin 
fraction may introduce systematic errors, especially in case of a varying twin 
fraction depending on the rotation of the crystal. Probably random noise is 
less harmful than systematic errors.

My 2 cts,
Herman

Von: CCP4 bulletin board 
[mailto:CCP4BB@JISCMAIL.AC.UK] Im Auftrag von 
Chris Fage
Gesendet: Dienstag, 11. Oktober 2016 10:40
An: CCP4BB@JISCMAIL.AC.UK
Betreff: Re: [ccp4bb] Why Does Detwinning Not Work?

Dear Jacob,

I'm not an expert on the topic, but from my experiences with twinning I can 
agree with you. I recently solved my second twinned structure by MR (twin 
fraction of 0.43, as estimated by Xtriage). Performing twin refinement in 
Refmac or phenix.refine dropped the R-factors, as expected, but worsened the 
geometry considerably without a noticeable improvement in the maps. For this 
reason, I opted *not* to go with the twin refinement... I don't know if others 
would make the same choice, though it seemed reasonable to me. Besides, my 
Rwork/Rfree is down to 0.25/0.29, which ain't too shabby for 2.6 A resolution.

Cheers,
Chris

On Tue, Oct 11, 2016 at 2:15 AM, Keller, Jacob 
mailto:kell...@janelia.hhmi.org>> wrote

[ccp4bb] AW: [ccp4bb] Why Does Detwinning Not Work?

[Herman . Schreuder]

Dear Bernard et al.,
I thought that in twinned refinement, no detwinning was performed, but that 
twinning was somehow incorporated in the refinement targets.
Of course, after refinement detwinning has to be done so that we human beings 
with limited innate detwinning faculties are able interpret the electron 
density maps.
If this is not true, we may have to look into Shelx for true twinned refinement.

Best,
Herman



Von: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] Im Auftrag von Soisson, 
Stephen M
Gesendet: Dienstag, 11. Oktober 2016 15:18
An: CCP4BB@JISCMAIL.AC.UK
Betreff: Re: [ccp4bb] Why Does Detwinning Not Work?

I seem to recall that Gerard was also looking at incorporating proper ML 
refinement for twinned data into the Global Phasing software, but I’m not sure 
on the status.

Best,

Steve

From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Bernhard 
Rupp
Sent: Tuesday, October 11, 2016 8:09 AM
To: CCP4BB@JISCMAIL.AC.UK
Subject: Re: [ccp4bb] Why Does Detwinning Not Work?

Tom Terwilliger recently pointed me to a relevant discussion on the phenix bb:

http://phenix-online.org/pipermail/phenixbb/2013-May/019836.html​

In essence, in case of detwinning, the refinement target is not a ML target 
anymore. With
the model being used as a basis for the detwinning of Fs, the refi procedure 
becomes susceptible
to bias.

I do not know what the current state is of developing the ML target for  
refining against twinned (I, F) data is.
Garib, Randy, perhaps?

Thx, BR

From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of 
herman.schreu...@sanofi.com
Sent: Tuesday, October 11, 2016 1:23 PM
To: CCP4BB@JISCMAIL.AC.UK
Subject: [ccp4bb] AW: [ccp4bb] AW: [ccp4bb] Why Does Detwinning Not Work?

Normally, twinned refinement is the way to go. However, if the maps don’t 
become clearer and without twinned refinement the R/Rfrees are already 
0.25/0.29, there might be some other problem. Here I would be more cautious.

Herman

Von: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] Im Auftrag von Eleanor 
Dodson
Gesendet: Dienstag, 11. Oktober 2016 13:09
An: CCP4BB@JISCMAIL.AC.UK
Betreff: Re: [ccp4bb] AW: [ccp4bb] Why Does Detwinning Not Work?

Search for: "experimental phasing with detwinned data" and you will find some 
hits.
You need a low degree of twinning, and a strong sub-structure signal..
Re MR solutions - it is usually possible to solve  the structure providing you 
get the space group right, but in my experience the maps are clearer if you do 
twinned refinement. I cant see any reason not to use it?
Eleanor

On 11 October 2016 at 10:05, 
mailto:herman.schreu...@sanofi.com>> wrote:
Dear Jacob,

I agree with Chris. In my experience for MR, twinning is just like having a 
space group with one extra 2-fold (or other twin operator) so MR is indeed 
largely immune to twinning. Also the maps, calculated with uncorrected data, 
often look surprisingly good, just having a higher level of random noise.

I did not do the math, but my feeling is that the (greatly) inflated 
measurement errors (exploding as you mention near a twin fraction of 0.5) make 
direct phasing methods, that are often at the very limit of useable signal to 
noise ratio, fail after detwinning.  Also, an incorrectly estimated twin 
fraction may introduce systematic errors, especially in case of a varying twin 
fraction depending on the rotation of the crystal. Probably random noise is 
less harmful than systematic errors.

My 2 cts,
Herman

Von: CCP4 bulletin board 
[mailto:CCP4BB@JISCMAIL.AC.UK] Im Auftrag von 
Chris Fage
Gesendet: Dienstag, 11. Oktober 2016 10:40
An: CCP4BB@JISCMAIL.AC.UK
Betreff: Re: [ccp4bb] Why Does Detwinning Not Work?

Dear Jacob,

I'm not an expert on the topic, but from my experiences with twinning I can 
agree with you. I recently solved my second twinned structure by MR (twin 
fraction of 0.43, as estimated by Xtriage). Performing twin refinement in 
Refmac or phenix.refine dropped the R-factors, as expected, but worsened the 
geometry considerably without a noticeable improvement in the maps. For this 
reason, I opted *not* to go with the twin refinement... I don't know if others 
would make the same choice, though it seemed reasonable to me. Besides, my 
Rwork/Rfree is down to 0.25/0.29, which ain't too shabby for 2.6 A resolution.

Cheers,
Chris

On Tue, Oct 11, 2016 at 2:15 AM, Keller, Jacob 
mailto:kell...@janelia.hhmi.org>> wrote:
Dear Crystallographers,

Based on some data sets I have looked at and anecdotal-type evidence here and 
there I have gotten the impression that detwinning does not help in structure 
solution. (Please let me know if you have a case where detwinning saved the 
day.) Is there a clear answer to this enigma anywhere, to anyone’s knowledge? 
Wouldn’t it seem that *any*

[ccp4bb] Occasional Support for Minstrel Imagers?

[Ambrose Cole]

Hi all, sorry for being slightly off topic but I have a question for UK labs 
who have Rigaku Minstrel imager systems.  To get material support on older 
systems we will now have to move onto a full service contract, we were 
previously on software support, calling for material support if needed (we 
haven’t needed any).  We were wondering whether anybody had experience of 
alternative support providers who could be called upon for general 
robotics/imaging glitches?  If not we’ll have to decide whether it’s cost 
effective to go for the full cover.

thanks in advance,

Ambrose

   
Ambrose Cole
X-Ray Laboratory Manager
Birkbeck College

Tel: 0207 631 6458
E-Mail: a.c...@mail.cryst.bbk.ac.uk

Re: [ccp4bb] Why Does Detwinning Not Work?

[Soisson, Stephen M]

I seem to recall that Gerard was also looking at incorporating proper ML 
refinement for twinned data into the Global Phasing software, but I’m not sure 
on the status.

Best,

Steve

From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Bernhard 
Rupp
Sent: Tuesday, October 11, 2016 8:09 AM
To: CCP4BB@JISCMAIL.AC.UK
Subject: Re: [ccp4bb] Why Does Detwinning Not Work?

Tom Terwilliger recently pointed me to a relevant discussion on the phenix bb:

http://phenix-online.org/pipermail/phenixbb/2013-May/019836.html​

In essence, in case of detwinning, the refinement target is not a ML target 
anymore. With
the model being used as a basis for the detwinning of Fs, the refi procedure 
becomes susceptible
to bias.

I do not know what the current state is of developing the ML target for  
refining against twinned (I, F) data is.
Garib, Randy, perhaps?

Thx, BR

From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of 
herman.schreu...@sanofi.com
Sent: Tuesday, October 11, 2016 1:23 PM
To: CCP4BB@JISCMAIL.AC.UK
Subject: [ccp4bb] AW: [ccp4bb] AW: [ccp4bb] Why Does Detwinning Not Work?

Normally, twinned refinement is the way to go. However, if the maps don’t 
become clearer and without twinned refinement the R/Rfrees are already 
0.25/0.29, there might be some other problem. Here I would be more cautious.

Herman

Von: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] Im Auftrag von Eleanor 
Dodson
Gesendet: Dienstag, 11. Oktober 2016 13:09
An: CCP4BB@JISCMAIL.AC.UK
Betreff: Re: [ccp4bb] AW: [ccp4bb] Why Does Detwinning Not Work?

Search for: "experimental phasing with detwinned data" and you will find some 
hits.
You need a low degree of twinning, and a strong sub-structure signal..
Re MR solutions - it is usually possible to solve  the structure providing you 
get the space group right, but in my experience the maps are clearer if you do 
twinned refinement. I cant see any reason not to use it?
Eleanor

On 11 October 2016 at 10:05, 
mailto:herman.schreu...@sanofi.com>> wrote:
Dear Jacob,

I agree with Chris. In my experience for MR, twinning is just like having a 
space group with one extra 2-fold (or other twin operator) so MR is indeed 
largely immune to twinning. Also the maps, calculated with uncorrected data, 
often look surprisingly good, just having a higher level of random noise.

I did not do the math, but my feeling is that the (greatly) inflated 
measurement errors (exploding as you mention near a twin fraction of 0.5) make 
direct phasing methods, that are often at the very limit of useable signal to 
noise ratio, fail after detwinning.  Also, an incorrectly estimated twin 
fraction may introduce systematic errors, especially in case of a varying twin 
fraction depending on the rotation of the crystal. Probably random noise is 
less harmful than systematic errors.

My 2 cts,
Herman

Von: CCP4 bulletin board 
[mailto:CCP4BB@JISCMAIL.AC.UK] Im Auftrag von 
Chris Fage
Gesendet: Dienstag, 11. Oktober 2016 10:40
An: CCP4BB@JISCMAIL.AC.UK
Betreff: Re: [ccp4bb] Why Does Detwinning Not Work?

Dear Jacob,

I'm not an expert on the topic, but from my experiences with twinning I can 
agree with you. I recently solved my second twinned structure by MR (twin 
fraction of 0.43, as estimated by Xtriage). Performing twin refinement in 
Refmac or phenix.refine dropped the R-factors, as expected, but worsened the 
geometry considerably without a noticeable improvement in the maps. For this 
reason, I opted *not* to go with the twin refinement... I don't know if others 
would make the same choice, though it seemed reasonable to me. Besides, my 
Rwork/Rfree is down to 0.25/0.29, which ain't too shabby for 2.6 A resolution.

Cheers,
Chris

On Tue, Oct 11, 2016 at 2:15 AM, Keller, Jacob 
mailto:kell...@janelia.hhmi.org>> wrote:
Dear Crystallographers,

Based on some data sets I have looked at and anecdotal-type evidence here and 
there I have gotten the impression that detwinning does not help in structure 
solution. (Please let me know if you have a case where detwinning saved the 
day.) Is there a clear answer to this enigma anywhere, to anyone’s knowledge? 
Wouldn’t it seem that *any* detwinning would be better than *no* detwinning? I 
understand that the errors explode as one approaches 50% twins and does 
detwinning, but still, I don’t think one *loses* information by detwinning, 
right? Take the case of a 33% twin: since the twin-reflections are on average 
about half the intensity of the non-twin, and since they are generally not 
correlated in intensity, isn’t this like having noise added at 50% of the 
measured intensity? So why does detwinning make things worse generally? Is 
there something wrong in the assumptions underlying the detwinning algorithm, 
or perhaps something about the calculation that throws things off?

A related s

Re: [ccp4bb] Why Does Detwinning Not Work?

[Bernhard Rupp]

Tom Terwilliger recently pointed me to a relevant discussion on the phenix bb:

 

  
http://phenix-online.org/pipermail/phenixbb/2013-May/019836.html​

 

In essence, in case of detwinning, the refinement target is not a ML target 
anymore. With

the model being used as a basis for the detwinning of Fs, the refi procedure 
becomes susceptible 

to bias.

 

I do not know what the current state is of developing the ML target for  
refining against twinned (I, F) data is.

Garib, Randy, perhaps?

 

Thx, BR

 

From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of 
herman.schreu...@sanofi.com
Sent: Tuesday, October 11, 2016 1:23 PM
To: CCP4BB@JISCMAIL.AC.UK
Subject: [ccp4bb] AW: [ccp4bb] AW: [ccp4bb] Why Does Detwinning Not Work?

 

Normally, twinned refinement is the way to go. However, if the maps don’t 
become clearer and without twinned refinement the R/Rfrees are already 
0.25/0.29, there might be some other problem. Here I would be more cautious.

 

Herman

 

Von: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] Im Auftrag von Eleanor 
Dodson
Gesendet: Dienstag, 11. Oktober 2016 13:09
An: CCP4BB@JISCMAIL.AC.UK
Betreff: Re: [ccp4bb] AW: [ccp4bb] Why Does Detwinning Not Work?

 

Search for: "experimental phasing with detwinned data" and you will find some 
hits.

You need a low degree of twinning, and a strong sub-structure signal.. 

Re MR solutions - it is usually possible to solve  the structure providing you 
get the space group right, but in my experience the maps are clearer if you do 
twinned refinement. I cant see any reason not to use it?

Eleanor

 

On 11 October 2016 at 10:05,  wrote:

Dear Jacob,

 

I agree with Chris. In my experience for MR, twinning is just like having a 
space group with one extra 2-fold (or other twin operator) so MR is indeed 
largely immune to twinning. Also the maps, calculated with uncorrected data, 
often look surprisingly good, just having a higher level of random noise.

 

I did not do the math, but my feeling is that the (greatly) inflated 
measurement errors (exploding as you mention near a twin fraction of 0.5) make 
direct phasing methods, that are often at the very limit of useable signal to 
noise ratio, fail after detwinning.  Also, an incorrectly estimated twin 
fraction may introduce systematic errors, especially in case of a varying twin 
fraction depending on the rotation of the crystal. Probably random noise is 
less harmful than systematic errors.

 

My 2 cts,

Herman

 

Von: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] Im Auftrag von Chris 
Fage
Gesendet: Dienstag, 11. Oktober 2016 10:40
An: CCP4BB@JISCMAIL.AC.UK
Betreff: Re: [ccp4bb] Why Does Detwinning Not Work?

 

Dear Jacob,

 

I'm not an expert on the topic, but from my experiences with twinning I can 
agree with you. I recently solved my second twinned structure by MR (twin 
fraction of 0.43, as estimated by Xtriage). Performing twin refinement in 
Refmac or phenix.refine dropped the R-factors, as expected, but worsened the 
geometry considerably without a noticeable improvement in the maps. For this 
reason, I opted *not* to go with the twin refinement... I don't know if others 
would make the same choice, though it seemed reasonable to me. Besides, my 
Rwork/Rfree is down to 0.25/0.29, which ain't too shabby for 2.6 A resolution.

 

Cheers,

Chris

 

On Tue, Oct 11, 2016 at 2:15 AM, Keller, Jacob  wrote:

Dear Crystallographers,

 

Based on some data sets I have looked at and anecdotal-type evidence here and 
there I have gotten the impression that detwinning does not help in structure 
solution. (Please let me know if you have a case where detwinning saved the 
day.) Is there a clear answer to this enigma anywhere, to anyone’s knowledge? 
Wouldn’t it seem that *any* detwinning would be better than *no* detwinning? I 
understand that the errors explode as one approaches 50% twins and does 
detwinning, but still, I don’t think one *loses* information by detwinning, 
right? Take the case of a 33% twin: since the twin-reflections are on average 
about half the intensity of the non-twin, and since they are generally not 
correlated in intensity, isn’t this like having noise added at 50% of the 
measured intensity? So why does detwinning make things worse generally? Is 
there something wrong in the assumptions underlying the detwinning algorithm, 
or perhaps something about the calculation that throws things off?

 

A related sub-enigma: why is MR generally immune to twinning, but anomalous 
methods are susceptible?

 

All the best,

 

Jacob Keller

 

***

Jacob Pearson Keller, PhD

Research Scientist

HHMI Janelia Research Campus / Looger lab

Phone: (571)209-4000 x3159  

Email:   kell...@janelia.hhmi.org

***

 

 

 

[ccp4bb] AW: [ccp4bb] AW: [ccp4bb] Why Does Detwinning Not Work?

[Herman . Schreuder]

Normally, twinned refinement is the way to go. However, if the maps don’t 
become clearer and without twinned refinement the R/Rfrees are already 
0.25/0.29, there might be some other problem. Here I would be more cautious.

Herman

Von: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] Im Auftrag von Eleanor 
Dodson
Gesendet: Dienstag, 11. Oktober 2016 13:09
An: CCP4BB@JISCMAIL.AC.UK
Betreff: Re: [ccp4bb] AW: [ccp4bb] Why Does Detwinning Not Work?

Search for: "experimental phasing with detwinned data" and you will find some 
hits.
You need a low degree of twinning, and a strong sub-structure signal..
Re MR solutions - it is usually possible to solve  the structure providing you 
get the space group right, but in my experience the maps are clearer if you do 
twinned refinement. I cant see any reason not to use it?
Eleanor

On 11 October 2016 at 10:05, 
mailto:herman.schreu...@sanofi.com>> wrote:
Dear Jacob,

I agree with Chris. In my experience for MR, twinning is just like having a 
space group with one extra 2-fold (or other twin operator) so MR is indeed 
largely immune to twinning. Also the maps, calculated with uncorrected data, 
often look surprisingly good, just having a higher level of random noise.

I did not do the math, but my feeling is that the (greatly) inflated 
measurement errors (exploding as you mention near a twin fraction of 0.5) make 
direct phasing methods, that are often at the very limit of useable signal to 
noise ratio, fail after detwinning.  Also, an incorrectly estimated twin 
fraction may introduce systematic errors, especially in case of a varying twin 
fraction depending on the rotation of the crystal. Probably random noise is 
less harmful than systematic errors.

My 2 cts,
Herman

Von: CCP4 bulletin board 
[mailto:CCP4BB@JISCMAIL.AC.UK] Im Auftrag von 
Chris Fage
Gesendet: Dienstag, 11. Oktober 2016 10:40
An: CCP4BB@JISCMAIL.AC.UK
Betreff: Re: [ccp4bb] Why Does Detwinning Not Work?

Dear Jacob,

I'm not an expert on the topic, but from my experiences with twinning I can 
agree with you. I recently solved my second twinned structure by MR (twin 
fraction of 0.43, as estimated by Xtriage). Performing twin refinement in 
Refmac or phenix.refine dropped the R-factors, as expected, but worsened the 
geometry considerably without a noticeable improvement in the maps. For this 
reason, I opted *not* to go with the twin refinement... I don't know if others 
would make the same choice, though it seemed reasonable to me. Besides, my 
Rwork/Rfree is down to 0.25/0.29, which ain't too shabby for 2.6 A resolution.

Cheers,
Chris

On Tue, Oct 11, 2016 at 2:15 AM, Keller, Jacob 
mailto:kell...@janelia.hhmi.org>> wrote:
Dear Crystallographers,

Based on some data sets I have looked at and anecdotal-type evidence here and 
there I have gotten the impression that detwinning does not help in structure 
solution. (Please let me know if you have a case where detwinning saved the 
day.) Is there a clear answer to this enigma anywhere, to anyone’s knowledge? 
Wouldn’t it seem that *any* detwinning would be better than *no* detwinning? I 
understand that the errors explode as one approaches 50% twins and does 
detwinning, but still, I don’t think one *loses* information by detwinning, 
right? Take the case of a 33% twin: since the twin-reflections are on average 
about half the intensity of the non-twin, and since they are generally not 
correlated in intensity, isn’t this like having noise added at 50% of the 
measured intensity? So why does detwinning make things worse generally? Is 
there something wrong in the assumptions underlying the detwinning algorithm, 
or perhaps something about the calculation that throws things off?

A related sub-enigma: why is MR generally immune to twinning, but anomalous 
methods are susceptible?

All the best,

Jacob Keller

***
Jacob Pearson Keller, PhD
Research Scientist
HHMI Janelia Research Campus / Looger lab
Phone: (571)209-4000 x3159
Email: kell...@janelia.hhmi.org
***

Re: [ccp4bb] AW: [ccp4bb] Why Does Detwinning Not Work?

[Eleanor Dodson]

Search for: "experimental phasing with detwinned data" and you will find
some hits.
You need a low degree of twinning, and a strong sub-structure signal..

Re MR solutions - it is usually possible to solve  the structure providing
you get the space group right, but in my experience the maps are clearer if
you do twinned refinement. I cant see any reason not to use it?
Eleanor


On 11 October 2016 at 10:05,  wrote:

> Dear Jacob,
>
>
>
> I agree with Chris. In my experience for MR, twinning is just like having
> a space group with one extra 2-fold (or other twin operator) so MR is
> indeed largely immune to twinning. Also the maps, calculated with
> uncorrected data, often look surprisingly good, just having a higher level
> of random noise.
>
>
>
> I did not do the math, but my feeling is that the (greatly) inflated
> measurement errors (exploding as you mention near a twin fraction of 0.5)
> make direct phasing methods, that are often at the very limit of useable
> signal to noise ratio, fail after detwinning.  Also, an incorrectly
> estimated twin fraction may introduce systematic errors, especially in case
> of a varying twin fraction depending on the rotation of the crystal.
> Probably random noise is less harmful than systematic errors.
>
>
>
> My 2 cts,
>
> Herman
>
>
>
> *Von:* CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] *Im Auftrag von
> *Chris Fage
> *Gesendet:* Dienstag, 11. Oktober 2016 10:40
> *An:* CCP4BB@JISCMAIL.AC.UK
> *Betreff:* Re: [ccp4bb] Why Does Detwinning Not Work?
>
>
>
> Dear Jacob,
>
>
>
> I'm not an expert on the topic, but from my experiences with twinning I
> can agree with you. I recently solved my second twinned structure by MR
> (twin fraction of 0.43, as estimated by Xtriage). Performing twin
> refinement in Refmac or phenix.refine dropped the R-factors, as expected,
> but worsened the geometry considerably without a noticeable improvement in
> the maps. For this reason, I opted *not* to go with the twin refinement...
> I don't know if others would make the same choice, though it seemed
> reasonable to me. Besides, my Rwork/Rfree is down to 0.25/0.29, which ain't
> too shabby for 2.6 A resolution.
>
>
>
> Cheers,
>
> Chris
>
>
>
> On Tue, Oct 11, 2016 at 2:15 AM, Keller, Jacob 
> wrote:
>
> Dear Crystallographers,
>
>
>
> Based on some data sets I have looked at and anecdotal-type evidence here
> and there I have gotten the impression that detwinning does not help in
> structure solution. (Please let me know if you have a case where detwinning
> saved the day.) Is there a clear answer to this enigma anywhere, to
> anyone’s knowledge? Wouldn’t it seem that **any** detwinning would be
> better than **no** detwinning? I understand that the errors explode as
> one approaches 50% twins and does detwinning, but still, I don’t think one *
> *loses** information by detwinning, right? Take the case of a 33% twin:
> since the twin-reflections are on average about half the intensity of the
> non-twin, and since they are generally not correlated in intensity, isn’t
> this like having noise added at 50% of the measured intensity? So why does
> detwinning make things worse generally? Is there something wrong in the
> assumptions underlying the detwinning algorithm, or perhaps something about
> the calculation that throws things off?
>
>
>
> A related sub-enigma: why is MR generally immune to twinning, but
> anomalous methods are susceptible?
>
>
>
> All the best,
>
>
>
> Jacob Keller
>
>
>
> ***
>
> Jacob Pearson Keller, PhD
>
> Research Scientist
>
> HHMI Janelia Research Campus / Looger lab
>
> Phone: (571)209-4000 x3159
>
> Email: kell...@janelia.hhmi.org
>
> ***
>
>
>
>
>

Re: [ccp4bb] Why Does Detwinning Not Work?

[Vellieux Frédéric]

Hello Jacob,

Quoting you, "Please let me know if you have a case where detwinning saved the 
day".

Well you asked for it so here is one example where twinning saved the day: 
"Crystal structure of pb9..." by Flayhan et al. (2014), J. Virol. 88 (2), 
820-828. Without detwinning I think there would have been no crystal structure 
in the end...

Cheers,

Fred.

From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Keller, 
Jacob
Sent: Tuesday, October 11, 2016 2:15 AM
To: CCP4BB@JISCMAIL.AC.UK
Subject: [ccp4bb] Why Does Detwinning Not Work?

Dear Crystallographers,

Based on some data sets I have looked at and anecdotal-type evidence here and 
there I have gotten the impression that detwinning does not help in structure 
solution. (Please let me know if you have a case where detwinning saved the 
day.) Is there a clear answer to this enigma anywhere, to anyone's knowledge? 
Wouldn't it seem that *any* detwinning would be better than *no* detwinning? I 
understand that the errors explode as one approaches 50% twins and does 
detwinning, but still, I don't think one *loses* information by detwinning, 
right? Take the case of a 33% twin: since the twin-reflections are on average 
about half the intensity of the non-twin, and since they are generally not 
correlated in intensity, isn't this like having noise added at 50% of the 
measured intensity? So why does detwinning make things worse generally? Is 
there something wrong in the assumptions underlying the detwinning algorithm, 
or perhaps something about the calculation that throws things off?

A related sub-enigma: why is MR generally immune to twinning, but anomalous 
methods are susceptible?

All the best,

Jacob Keller

***
Jacob Pearson Keller, PhD
Research Scientist
HHMI Janelia Research Campus / Looger lab
Phone: (571)209-4000 x3159
Email: kell...@janelia.hhmi.org
***

-

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zpráva nebo její prílohy pouze informativní charakter. Tato zpráva ani její 
prílohy v zádném ohledu Biotechnologický ústav AV CR, v. v. i. k nicemu 
nezavazují. Text této zprávy nebo jejích príloh není návrhem na uzavrení 
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jednáním smerujícím k uzavrení jakékoliv smlouvy a nezakládá predsmluvní 
odpovednost Biotechnologického ústavu AV CR, v. v. i.

Disclaimer: If not expressly stated otherwise, this e-mail message (including 
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[ccp4bb] PhD and Postdoc positions in Structural and Single-molecule biology

[Sebastian Deindl]

Dear colleagues,

My group is currently looking for PhD students and postdocs interested in 
either structural biology or single-molecule approaches to study chromatin 
complexes in the framework of an ERC-funded project.
If you could kindly pass this message on to interested and well-suited 
individuals, I would greatly appreciate it. Please feel free to circulate this 
message within your department.

Thank you very much!

Sebastian

https://www.scilifelab.se/calander/postdoctoral-researcher-in-single-molecule-studies-of-chromatin-complexes/
https://www.scilifelab.se/calander/postdoctoral-researcher-in-integrated-structural-biology-of-chromatin-complexes/
https://www.scilifelab.se/calander/phd-student-position-in-single-molecule-studies-of-chromatin-complexes/
https://www.scilifelab.se/calander/phd-student-position-in-integrated-structural-biology-of-chromatin-complexes/

=
Sebastian Deindl, Ph.D.
Assistant Professor
Department of Cell and Molecular Biology,
Program for Computational and Systems Biology
Uppsala University
Phone: +46 (0) 18 471 6681
Email: sebastian.dei...@icm.uu.se
Web: http://deindl-lab.com

[ccp4bb] PhD position available at SGC, University of Oxford

[Alex Bullock]

A scholarship-funded DPhil (PhD) studentship position is available at the SGC, 
University of Oxford, for the academic year starting October 2017.  The closing 
date for applications will be 12 noon UK time, 6th January 2017. Interviews 
will take place on 24th & 25th January 2017.  Scholarship is available for UK 
nationals only, but funding options are available for other nationalities.  
Application and project details are copied below:

Characterisation of the drug target ACVR1/ALK2

Supervisors: Dr Alex Bullock, Dr Gillian Farnie

Project Overview

A multidisciplinary DPhil project is available using structural, cellular and 
chemical biology approaches to advance our ongoing drug discovery efforts 
targeting the BMP receptor kinase ALK2, encoded by the gene ACVR1. Gain of 
function mutations in the intracellular kinase domain of ALK2/ACVR1 cause the 
childhood brain tumour DIPG (diffuse intrinsic pontine glioma) and the rare 
bone disease FOP (fibrodysplasia ossificans progressiva) (Nat Genet. 2014; 46, 
457-61). There are currently no effective treatments for either condition and 
prognosis is poor.

The ALK2 kinase is a member of the BMP/TGF-beta receptor family that activates 
both the Smad transcription factor and p38 MAPK signaling pathways by 
phosphorylation. Ligands of the BMP/TGF-β superfamily (BMPs, Nodal, Activins, 
GDFs, TGF-βs) are secreted growth factors well known for their roles in 
determining stem cell fate and tissue repair.  While some members such as GDF11 
have been controversially famed as the "elixir of youth" (Science 2014; 344, 
649-52), many are oppositely linked to human disease.

You will elucidate the molecular mechanisms that cause ALK2 deregulation and 
characterize the actions and potency of small molecule ALK2 inhibitors in 
development in our group (J Med Chem 2014; 57, 7900-15).  Key questions 
include: how does ALK2 activity drive cancer? How do the disease mutations 
affect the receptor's structure and function?  How are different signalling 
pathways affected?  What protein-protein interactions are changed? Why do 
oncogenic ALK2/ACVR1 mutations occur together with specific Histone H3 K27M 
mutations? Do epigenetic inhibitors improve the efficacy of ALK2 inhibitors?

Training Opportunities

You will learn about protein structure, cellular signalling and drug discovery. 
Training will be given in all aspects of molecular biology from routine cloning 
and mutagenesis to protein expression and purification using bacterial and 
human cells. Wild-type and mutant proteins will be analysed using 
bioinformatic, cellular, biochemical and biophysical techniques (including mass 
spectrometry, fluorescence plate readers and calorimetry).  As part of the 
Structural Genomics Consortium (SGC) you will make use of state of art 
facilities for protein crystallisation, X-ray diffraction and structure 
determination. The student will also benefit from extensive collaborations with 
international collaborators, patient groups, clinicians and pharmaceutical 
companies. A named scholarship is available for this project for candidates 
with UK nationality and residency.

http://www.ndm.ox.ac.uk/for-applicants

For informal queries, contact: alex.bull...@sgc.ox.ac.uk

References

Sinha M, Jang YC, Oh J, Khong D, Wu EY, Manohar R, Miller C, Regalado SG, 
Loffredo FS, Pancoast JR, Hirshman MF, Lebowitz J, Shadrach JL, Cerletti M, Kim 
MJ, Serwold T, Goodyear LJ, Rosner B, Lee RT, Wagers AJ. (2014). Restoring 
systemic GDF11 levels reverses age-related dysfunction in mouse skeletal 
muscle. Science, 344, pp. 649-52.

Chaikuad A, Alfano I, Kerr G, Sanvitale CE, Boergermann JH, Triffitt JT, von 
Delft F, Knapp S, Knaus P, Bullock AN. (2012). Structure of the bone 
morphogenetic protein receptor ALK2 and implications for fibrodysplasia 
ossificans progressiva. J. Biol. Chem., 287, pp. 36990-8.

Mohedas AH, Wang Y, Sanvitale CE, Canning P, Choi S, Xing X, Bullock AN, Cuny 
GD, Yu PB. (2014). Structure-activity relationship of 
3,5-diaryl-2-aminopyridine ALK2 inhibitors reveals unaltered binding affinity 
for fibrodysplasia ossificans progressiva causing mutants. J. Med. Chem., 57, 
pp. 7900-15.

Chaikuad A, Bullock AN. (2016). Structural Basis of Intracellular TGF-β 
Signaling: Receptors and Smads. Cold Spring Harb Perspect Biol, [Epub]

Taylor KR, Vinci M, Bullock AN, Jones C. (2014). ACVR1 mutations in DIPG: 
lessons learned from FOP. Cancer Res., 74, pp. 4565-70.

Taylor KR, Mackay A, Truffaux N, Butterfield YS, Morozova O, Philippe C, Castel 
D, Grasso CS, Vinci M, Carvalho D, Carcaboso AM, de Torres C, Cruz O, Mora J, 
Entz-Werle N, Ingram WJ, Monje M, Hargrave D, Bullock AN, Puget S, Yip S, Jones 
C, Grill J. (2014). Recurrent activating ACVR1 mutations in diffuse intrinsic 
pontine glioma. Nat. Genet., 46, pp. 457-61.

[ccp4bb] AW: [ccp4bb] Why Does Detwinning Not Work?

[Herman . Schreuder]

Dear Jacob,

I agree with Chris. In my experience for MR, twinning is just like having a 
space group with one extra 2-fold (or other twin operator) so MR is indeed 
largely immune to twinning. Also the maps, calculated with uncorrected data, 
often look surprisingly good, just having a higher level of random noise.

I did not do the math, but my feeling is that the (greatly) inflated 
measurement errors (exploding as you mention near a twin fraction of 0.5) make 
direct phasing methods, that are often at the very limit of useable signal to 
noise ratio, fail after detwinning.  Also, an incorrectly estimated twin 
fraction may introduce systematic errors, especially in case of a varying twin 
fraction depending on the rotation of the crystal. Probably random noise is 
less harmful than systematic errors.

My 2 cts,
Herman

Von: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] Im Auftrag von Chris 
Fage
Gesendet: Dienstag, 11. Oktober 2016 10:40
An: CCP4BB@JISCMAIL.AC.UK
Betreff: Re: [ccp4bb] Why Does Detwinning Not Work?

Dear Jacob,

I'm not an expert on the topic, but from my experiences with twinning I can 
agree with you. I recently solved my second twinned structure by MR (twin 
fraction of 0.43, as estimated by Xtriage). Performing twin refinement in 
Refmac or phenix.refine dropped the R-factors, as expected, but worsened the 
geometry considerably without a noticeable improvement in the maps. For this 
reason, I opted *not* to go with the twin refinement... I don't know if others 
would make the same choice, though it seemed reasonable to me. Besides, my 
Rwork/Rfree is down to 0.25/0.29, which ain't too shabby for 2.6 A resolution.

Cheers,
Chris

On Tue, Oct 11, 2016 at 2:15 AM, Keller, Jacob 
mailto:kell...@janelia.hhmi.org>> wrote:
Dear Crystallographers,

Based on some data sets I have looked at and anecdotal-type evidence here and 
there I have gotten the impression that detwinning does not help in structure 
solution. (Please let me know if you have a case where detwinning saved the 
day.) Is there a clear answer to this enigma anywhere, to anyone’s knowledge? 
Wouldn’t it seem that *any* detwinning would be better than *no* detwinning? I 
understand that the errors explode as one approaches 50% twins and does 
detwinning, but still, I don’t think one *loses* information by detwinning, 
right? Take the case of a 33% twin: since the twin-reflections are on average 
about half the intensity of the non-twin, and since they are generally not 
correlated in intensity, isn’t this like having noise added at 50% of the 
measured intensity? So why does detwinning make things worse generally? Is 
there something wrong in the assumptions underlying the detwinning algorithm, 
or perhaps something about the calculation that throws things off?

A related sub-enigma: why is MR generally immune to twinning, but anomalous 
methods are susceptible?

All the best,

Jacob Keller

***
Jacob Pearson Keller, PhD
Research Scientist
HHMI Janelia Research Campus / Looger lab
Phone: (571)209-4000 x3159
Email: kell...@janelia.hhmi.org
***

Re: [ccp4bb] Why Does Detwinning Not Work?

[Chris Fage]

Sorry--I think you were referring to phasing, not refinement. I hope my
message is still relevant.

Cheers,
Chris

On Tue, Oct 11, 2016 at 10:39 AM, Chris Fage  wrote:

> Dear Jacob,
>
> I'm not an expert on the topic, but from my experiences with twinning I
> can agree with you. I recently solved my second twinned structure by MR
> (twin fraction of 0.43, as estimated by Xtriage). Performing twin
> refinement in Refmac or phenix.refine dropped the R-factors, as expected,
> but worsened the geometry considerably without a noticeable improvement in
> the maps. For this reason, I opted *not* to go with the twin refinement...
> I don't know if others would make the same choice, though it seemed
> reasonable to me. Besides, my Rwork/Rfree is down to 0.25/0.29, which ain't
> too shabby for 2.6 A resolution.
>
> Cheers,
> Chris
>
> On Tue, Oct 11, 2016 at 2:15 AM, Keller, Jacob 
> wrote:
>
>> Dear Crystallographers,
>>
>>
>>
>> Based on some data sets I have looked at and anecdotal-type evidence here
>> and there I have gotten the impression that detwinning does not help in
>> structure solution. (Please let me know if you have a case where detwinning
>> saved the day.) Is there a clear answer to this enigma anywhere, to
>> anyone’s knowledge? Wouldn’t it seem that **any** detwinning would be
>> better than **no** detwinning? I understand that the errors explode as
>> one approaches 50% twins and does detwinning, but still, I don’t think one *
>> *loses** information by detwinning, right? Take the case of a 33% twin:
>> since the twin-reflections are on average about half the intensity of the
>> non-twin, and since they are generally not correlated in intensity, isn’t
>> this like having noise added at 50% of the measured intensity? So why does
>> detwinning make things worse generally? Is there something wrong in the
>> assumptions underlying the detwinning algorithm, or perhaps something about
>> the calculation that throws things off?
>>
>>
>>
>> A related sub-enigma: why is MR generally immune to twinning, but
>> anomalous methods are susceptible?
>>
>>
>>
>> All the best,
>>
>>
>>
>> Jacob Keller
>>
>>
>>
>> ***
>>
>> Jacob Pearson Keller, PhD
>>
>> Research Scientist
>>
>> HHMI Janelia Research Campus / Looger lab
>>
>> Phone: (571)209-4000 x3159
>>
>> Email: kell...@janelia.hhmi.org
>>
>> ***
>>
>>
>>
>
>

[ccp4bb] PhD position available - another one

[Apirat Chaikuad]

Posted on behalf of Prof. Stefan Knapp

Note that this is another PhD position (not the same one as previous post last 
week).

The Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, 
Germany, currently offers a position for a PhD student in the research group of 
Prof Knapp (http://www.uni-frankfurt.de/53483664/Knapp). The position is 
available from January and the appointment is funded for 3 years by the Marie 
Skłodowska-Curie Actions (MSCA) Innovative Training Networks (ITN) grant. 
PDZnet (Unraveling Principles of PDZ-mediated Cell Signaling).
The project is embedded into a highly interactive European training program 
involving internationally well recognized laboratories and companies.  The 
advertised position aims to study the function and structure of modular 
proteins that organize multiple PDZ domains into supramodules. We will study 
the structure and substrate specificity of these multi-domain assemblies with 
the goal to elucidate their function in cellular signalling and to exploit the 
possibility for the development of protein interaction inhibitors targeting PDZ 
supramodules.
The ideal candidate would have a Master degree in Chemistry, Biochemistry or 
Biophysics and experience in protein biochemistry and protein expression. We 
are an international team and good knowledge of English as well as excellent 
communication skills will be essential. Female candidates are especially 
encouraged to apply. Precedence will be given to handicapped candidates at 
equal qualification.

The planned research will be done in a highly stimulating and international 
research environment, integrated in the life science campus Riedberg Interested 
candidates are encouraged to submit their CVs to the following e-mail address: 
kn...@pharmchem.uni-frankfurt.de

Closing date for application is 31st October 2016

Regards,
Prof. Stefan Knapp.

Re: [ccp4bb] Why Does Detwinning Not Work?

[Chris Fage]

Dear Jacob,

I'm not an expert on the topic, but from my experiences with twinning I can
agree with you. I recently solved my second twinned structure by MR (twin
fraction of 0.43, as estimated by Xtriage). Performing twin refinement in
Refmac or phenix.refine dropped the R-factors, as expected, but worsened
the geometry considerably without a noticeable improvement in the maps. For
this reason, I opted *not* to go with the twin refinement... I don't know
if others would make the same choice, though it seemed reasonable to me.
Besides, my Rwork/Rfree is down to 0.25/0.29, which ain't too shabby for
2.6 A resolution.

Cheers,
Chris

On Tue, Oct 11, 2016 at 2:15 AM, Keller, Jacob 
wrote:

> Dear Crystallographers,
>
>
>
> Based on some data sets I have looked at and anecdotal-type evidence here
> and there I have gotten the impression that detwinning does not help in
> structure solution. (Please let me know if you have a case where detwinning
> saved the day.) Is there a clear answer to this enigma anywhere, to
> anyone’s knowledge? Wouldn’t it seem that **any** detwinning would be
> better than **no** detwinning? I understand that the errors explode as
> one approaches 50% twins and does detwinning, but still, I don’t think one *
> *loses** information by detwinning, right? Take the case of a 33% twin:
> since the twin-reflections are on average about half the intensity of the
> non-twin, and since they are generally not correlated in intensity, isn’t
> this like having noise added at 50% of the measured intensity? So why does
> detwinning make things worse generally? Is there something wrong in the
> assumptions underlying the detwinning algorithm, or perhaps something about
> the calculation that throws things off?
>
>
>
> A related sub-enigma: why is MR generally immune to twinning, but
> anomalous methods are susceptible?
>
>
>
> All the best,
>
>
>
> Jacob Keller
>
>
>
> ***
>
> Jacob Pearson Keller, PhD
>
> Research Scientist
>
> HHMI Janelia Research Campus / Looger lab
>
> Phone: (571)209-4000 x3159
>
> Email: kell...@janelia.hhmi.org
>
> ***
>
>
>