[ccp4bb] Postdoc position at Imperial College London
A Research Associate position in protein crystallography is available within the group of Prof. Paul Freemont (Division of Molecular Biosciences, Imperial College London: www.imperial.ac.uk/molecularbiosciences) as part of the Imperial College Small Molecule Cancer Drug Discovery Programme funded by CRUK and is available immediately for a period of 3 years, with a possibility of renewal for a further 2 years (subject to funding). The aim of the programme is to create a pipeline for small molecule anti-cancer drug discovery and development, using a chemistry-biology interface with protein crystallography to optimise lead compounds. The overall goal of the programme is to develop and test novel anti-cancer compounds in humans as led by clinicians in the Imperial College Cancer group at Hammersmith Hospital led by Prof. Charles Coombes. The small molecule programme is highly focused and will require the appointed research associate to work on a variety of protein targets in collaboration with clinical scientists as part of an interdisciplinary team that encompasses a major part of the drug discovery pipeline, including synthetic and medicinal chemistry, chemo- informatics, rational drug design, molecular and cell biology and clinical biochemistry. The successful candidate will have a PhD or equivalent qualification in a relevant research area and previous research experience in structural biology using primarily protein crystallography. The project will also require research experience and skills in recombinant protein expression, purification, crystallisation and small-ligand screening using protein crystallography and other biophysical methods. Further details and an application form can be obtained from the College employment website: http://www3.imperial.ac.uk/employment/research . Completed application forms accompanied by a curriculum vitae and the names and contact details of two referees should be sent to: Mrs Naomi Anderson-Eyles, Imperial College London, Room 503, Biochemistry Building, Exhibition Road, London, SW7 2AZ or by email to: [EMAIL PROTECTED] Closing date: 4 July 2008
Re: [ccp4bb] How to change R-free set?
It is important that your new smaller test set include only reflections
that were in your previous test set, and not include any of the previous
working reflections.
By now you probably have several replies detailing how to achieve this in ccp4.
If you happen to be using CNS, there is an easy way to pair down the free set:
Use the make_cv.inp script. Use a cv file with the old free set as input.
{===>} reflection_infile="oldfile.cv";
The old free set will probably be labeled "test". Make a new column
to hold the 2.5% flags:
{===>} test_set="test2p5";
Select the new set from the old set:
{* Additional selection for generation of test set *}
{===>} ref_sel=( test=1 );
select 50% of the reflections:
{===>} percentage=50.0;{50% of 5% is 2.5%}
and give a new name for the new file
{===>} reflection_outfile="newfile.cv";
I think those are the salient points, but if it doesn't work
email me and I'll send a working version
HTH,
ed
(formerly [EMAIL PROTECTED])
Jason C Porta wrote:
Hi all,
I am currently refining a high-resolution structure that has many
reflections (~180,000). I would like to halve the R-free set from 5% to
2.5%, and am unsure how to do so. Any advice will be greatly appreciated.
Jason Porta
Graduate Student
Dept. Biochemistry and Molecular Biology
University of Nebraska Medical Center
Omaha, NE 68198
[ccp4bb] Fw: Re: [ccp4bb] Structural importance of ordered water?
I suspect that in many cases the crystal is making the news instead on reporting the actual status of bound waters in fluid conditions. One should probably be looking at NMR structures for a more valid report of bound waters. Are there any reports of the comparison of the number of bound waters in crystal structures vs NMR structures? Paul Kraft --- On Tue, 6/17/08, Sanishvili, Ruslan <[EMAIL PROTECTED]> wrote: From: Sanishvili, Ruslan <[EMAIL PROTECTED]> Subject: Re: [ccp4bb] Structural importance of ordered water? To: CCP4BB@JISCMAIL.AC.UK Date: Tuesday, June 17, 2008, 5:16 PM Hi Richard and Colin, There are some "X-ray - visible" water networks described in 0.66 A structure of Aldose Reductase (Proteins. 2004 Jun 1;55(4):792-804) and I'm sure there are plenty of similar descriptions out there. I am not an expert by any means but I think the question of water contribution in protein stability is more complicated. If we look only at the protein and the bound to it water, our impressions may differ from when the rest of the solvent is considered. Surely protein-water system is energetically happier than protein-vacuum but I don't think protein-water is as happy as water-water. What is, for example, the penalty of removing a water molecule from water-water interactions and including it into water-protein networks? Some input from thermodynamics folks would be great here. Cheers, N. Ruslan Sanishvili (Nukri), Ph.D. GM/CA-CAT, Bld. 436, D007 Biosciences Division, ANL 9700 S. Cass Ave. Argonne, IL 60439 Tel: (630)252-0665 Fax: (630)252-0667 [EMAIL PROTECTED] -Original Message- From: CCP4 bulletin board [mailto:[EMAIL PROTECTED] On Behalf Of Nave, C (Colin) Sent: Tuesday, June 17, 2008 3:33 PM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] Structural importance of ordered water? Richard Not sure about chains but mutual hydrogen bonded networks (you mention networks) between protein, water (and ligand) surely occur. I think most self respecting waters would try and form more then two hydrogen bonds (rather then just be part of a chain) though one might not see all the (perhaps transient) bonds in an x-ray structure. These networks seem to form very easily in computer simulations where their dynamic behavior can be studied. Lots on "spanning water networks". So waters could link residues a considerable distance away but some of these waters might also join to other residues (the mutual hydrogen bonded network). Of course you are asking about direct x-ray evidence and this is more difficult. Fig. 1 in http://www.lsbu.ac.uk/water/protein.html gives an example. I would hope there are more recent ones which others will identify more easily than I can. Colin -Original Message- From: CCP4 bulletin board [mailto:[EMAIL PROTECTED] On Behalf Of Richard Gillilan Sent: 17 June 2008 20:05 To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Structural importance of ordered water? Direct hydrogen bonds between sidechains are obviously important to structural stability in proteins. From time to time I see cases of water-mediated bonds in which a single water molecule seems to play an important role (sometimes taking the place of a missing ligand atom in an apo structure, for example). But what about larger chains and networks of water? Assuming a structure is high enough in resolution and well-ordered enough to observe such things, has anyone systematically studied the structural importance of multiple water interactions (I do know of a paper by Faerman and Karplus back in 94, but perhaps there is more recent work). Has anyone here ever seen a plausible argument that a chain of several hydrogen-bonded waters enables residue A to interact with residue B, some considerable distance away? I have to say, I am skeptical of arguments based on water positions. Thanks Richard Gillilan MacCHESS This e-mail and any attachments may contain confidential, copyright and or privileged material, and are for the use of the intended addressee only. If you are not the intended addressee or an authorised recipient of the addressee please notify us of receipt by returning the e-mail and do not use, copy, retain, distribute or disclose the information in or attached to the e-mail. Any opinions expressed within this e-mail are those of the individual and not necessarily of Diamond Light Source Ltd. Diamond Light Source Ltd. cannot guarantee that this e-mail or any attachments are free from viruses and we cannot accept liability for any damage which you may sustain as a result of software viruses which may be transmitted in or with the message. Diamond Light Source Limited (company no. 4375679). Registered in England and Wales with its registered office at Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire, OX11 0DE, United Kingdom
Re: [ccp4bb] Fw: Re: [ccp4bb] Structural importance of ordered water?
On Wed, 18 Jun 2008, Paul Kraft wrote: Are there any reports of the comparison of the number of bound waters in crystal structures vs NMR structures? Paul Kraft this is discussed inter alia in : Mattos, C. & Ringe, D., Solvent Structure, in International Tables for Crystallography (Rossman, M. G. & Arnold, E., Eds). Kluwer Academic Publishers: Dordrecht p. 623-640 (2001). hth -bryan
Re: [ccp4bb] Structural importance of ordered water?
Title: Re: [ccp4bb] Fw: Re: [ccp4bb] Structural importance of ordered water? Some work has been done on collagen regarding its hydration structure: (crystal data) Bella, J. Brodsky, B. Berman, H.M.. Structure (3), 893-906 1995 (NMR) Peto, S. Gillis, P. Henri, V.P. . Biophys J. (57), 71-84, 1990 (NMR) Renou, J.P. Bonnet, M. Bielicki, G. Rochdi, A. Gatellier, P. Biopolymers (34), 1615-1626, 1994 ### Dr. Paul A. McEwan Protein Crystallography Group Office C58 Centre for Biomolecular Science University of Nottingham Nottingham NG7 2RD UK Tel: 0115 8232018 http://www.nottingham.ac.uk/pharmacy/research/medicinal-chemistry-structural-biology/structbio.php### This message has been checked for viruses but the contents of an attachment may still contain software viruses, which could damage your computer system: you are advised to perform your own checks. Email communications with the University of Nottingham may be monitored as permitted by UK legislation.
[ccp4bb] New Deadline - EMBO World Lecture Course
Dear all, there are still a few places left in the EMBO World Lecture Course on RECENT DEVELOPMENTS IN MACROMOLECULAR CRYSTALLOGRAPHY which I had announced earlier (see below). Check out the web page http:/cwp.embo.org/wpc08-02/ or contact me for further information. The NEW DEADLINE is Monday, June 23, 2008. It's a great opportunity. Cheers, Manfred. > > EMBO World Lecture Course on > > RECENT DEVELOPMENTS IN MACROMOLECULAR CRYSTALLOGRAPHY > > We would like to announce an EMBO World Lecture Course on > RECENT DEVELOPMENTS IN MACROMOLECULAR CRYSTALLOGRAPHY, which > will take place from Nov 09-14, 2008 in the town in Pune in > India, on the premises of the National Chemical Laboratory > NCL. This course consists of various lectures describing recent > methodological developments in the field from crystallization, to > diffraction data collection, structure determination and function > prediction from structure as well as lectures on recent > achievements in biology using X-ray diffraction techniques. > > Pune is located abour 150 km south of Mumbai (Bombay) on the > foothills of the Western valley of Maharashtra in Western > India. It is a city of great culture and is rich in tradition > and history as well as having a balanced climate. > > Due to space limitations, we can only accommodate up to 100 participants. > Preference will be given to applicants who wish to present their > own work. From the submitted abstracts a number of short talks > will be selected. Also, the three best posters will be awarded a > poster price. > > REGISTRATION for the course is now open. > > For more information and registration, please check the course > homepage http:/cwp.embo.org/wpc08-02/ or contact the organizers > >Manfred S. Weiss ([EMAIL PROTECTED]) >Paul A. Tucker ([EMAIL PROTECTED]) >Santosh Panjikar ([EMAIL PROTECTED]) >C. G. Suresh ([EMAIL PROTECTED]) >Sanjay N. Nene ([EMAIL PROTECTED]) > > Best regards, > > Manfred > > > * * > *Dr. Manfred S. Weiss * > * * > * Team Leader * > * * > * EMBL Hamburg OutstationFon: +49-40-89902-170 * > * c/o DESY, Notkestr. 85 Fax: +49-40-89902-149 * > * D-22603 Hamburg Email: [EMAIL PROTECTED] * > * GERMANY Web: www.embl-hamburg.de/~msweiss/ * > * * > > >
Re: [ccp4bb] Structural importance of ordered water?
> -Original Message- > From: [EMAIL PROTECTED] > [mailto:[EMAIL PROTECTED] On Behalf Of Sanishvili, Ruslan > Sent: 17 June 2008 22:17 > To: Nave, C (Colin); CCP4BB@JISCMAIL.AC.UK > Cc: Richard Gillilan > Subject: RE: [ccp4bb] Structural importance of ordered water? > > Surely protein-water > system is energetically happier than protein-vacuum but I don't think > protein-water is as happy as water-water. Hi, IMHO you can't make such blanket statements without some qualification. The very fact that a protein is soluble in water under given conditions implies that the protein-water interactions created upon dissolution are energetically more favourable (I'm talking about free energy of course) than the protein-protein and water-water interactions that they replace. Similarly, protein-water interactions are no doubt more favourable than a protein-vacuum interface if the protein surface in question contains H-bond donors/acceptors, but this is not true (at least not at normal pressures) if the protein surface is purely non-polar. This was convincingly demonstrated for a T4 lysozyme mutant (http://www.pnas.org/cgi/reprint/102/46/16668.pdf) where water molecules could only be induced (reversibly) to enter a large (160 Ang^3) rigid hydrophobic void in the protein's interior created by the L99A mutation by application of extreme external pressure (200 Mpascals, or 2000 x atmospheric pressure). Cheers -- Ian Disclaimer This communication is confidential and may contain privileged information intended solely for the named addressee(s). It may not be used or disclosed except for the purpose for which it has been sent. If you are not the intended recipient you must not review, use, disclose, copy, distribute or take any action in reliance upon it. If you have received this communication in error, please notify Astex Therapeutics Ltd by emailing [EMAIL PROTECTED] and destroy all copies of the message and any attached documents. Astex Therapeutics Ltd monitors, controls and protects all its messaging traffic in compliance with its corporate email policy. The Company accepts no liability or responsibility for any onward transmission or use of emails and attachments having left the Astex Therapeutics domain. Unless expressly stated, opinions in this message are those of the individual sender and not of Astex Therapeutics Ltd. The recipient should check this email and any attachments for the presence of computer viruses. Astex Therapeutics Ltd accepts no liability for damage caused by any virus transmitted by this email. E-mail is susceptible to data corruption, interception, unauthorized amendment, and tampering, Astex Therapeutics Ltd only send and receive e-mails on the basis that the Company is not liable for any such alteration or any consequences thereof. Astex Therapeutics Ltd., Registered in England at 436 Cambridge Science Park, Cambridge CB4 0QA under number 3751674
[ccp4bb] monomer library sketcher troubles
Hi all, our library sketcher all of a sudden started acting up after working just fine. - read in or draw a structure works fine, - Create library description - a message pops up: Error running Libcheck program see /tmp/jabendroth/7547_tmp Sorry - this means we can not list the monomers in the currently selected library - this file is shown below - if the warning message is dismissed, all the fields in the create library window are populated, hit run Error: can't read "monomer_lib(typelist): no such variable - the same happens on various computers and for different users Any ideas? Thanks a lot! Jan tmp file # --- LIBCHECK --- /Vers 4.1.3 ; 19.12.2002/ Do you want to have FILE-DOCUMENT /libcheck.doc/ ? //Y/A : N - means without DOC-file Y - with new contents A - means to keep old contents and add new information with DOC-file program creates batch file: libcheck.bat _DOC: # # Keywords: # #FILE_L: < > - additional library, " " means without this file #MON: < > - give info about this monomer # if = * , give list all monomers in the library #FILE_PDB: < > - input PDB_file ," " means without this file #FILE_SMILE: < > - input SMILE_file ," " means without this fil e # use keyword MON as compound_id #FILE_CIF: < > - input CIFile," " means without this file #FILE_CSD: < > - input CSD CIFile," " means without this file #HFLAG: /A/N - Y - hydrogen atoms where they are # A - with all hydrogen atoms # N - without hydrogen atoms #IND:/Y - Y - create index of mon_lib.cif # output file: "new_mon_lib_ind.cif" #FILE_O: - output files /library,coords,ps/, name without # extention #FILE_L2: < > - additional library (FILE_L) will be added to this library # in this case program performs only adding #ANGLE: <0.0> - rotation angle for picture ( around X ) #LIST: /S/L - S short output, L - long, M - medium #REF: /S,N,0 - 0 no refinement of new monomer # N only crd->ang and ang->crd # S plus torsion ref, Y plus restr.ref # #TEST: <0>- for program testing only #COOR: /Y- use Vobs from coords instead Videal #LCOOR: /N - Y use coords from lib description #NODIST: /Y - Y not read the distributed library # (only with FILE_L) #SRCH: /Y/0 - Y - global search, 0 - for MON from PDB_file # (only with NODIST = N) #--- type "keyword parameters" and/or --- #--- press key "CR" to run program --- --> --> MON : * - - Keywords: HFLAG : Y COOR : N LCOOR : Y SRCH : N REF : Y NODIST: N -- --- LIBRARY OF MONOMERS --- _lib_name mon_lib _lib_version 4.12 _lib_update 20/09/07 -- NUMBER OF MONOMERS IN THE LIBRARY : 2436 with complete description: 454 NUMBER OF MODIFICATIONS:47 NUMBER OF LINKS:64 ERROR: in LIB_CREATE_INDEX2: not memory enough: CCP4: Fatal error, see above.
