[phenixbb] Ligand restraints editing with REEL -summary

Joseph Brock joeylives2ride at hotmail.com
Tue Sep 28 18:07:45 PDT 2010 

Hi all,

I just wanted to post a quick summary of how my problem was resolved.

I later realised that the 'native glutahione' molecule I was transferring ligand restraints from was actually produced by eLBOW released under the Phenix package v1.4, and was therefore defined differently to those restraints created by v1.6.4-486.

I was advised by Nigel (author of eLBOW and REEL) to download the latest nightly build (dev-541) and create a clean subdirectory. Copying my model.pdb and data.mtz file into this, running phenix.ready_set on these files and running phenix.refine with the resulting .pdb and .cif  files, resulted in a ligand that was correctly restrained to refine into the density extremely well.

Hope this is of help to anyone with a similar problem.

Cheers,

Joe.

> From: phenixbb-request at phenix-online.org
> Subject: phenixbb Digest, Vol 58, Issue 18
> To: phenixbb at phenix-online.org
> Date: Sat, 18 Sep 2010 12:00:01 -0700
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> Today's Topics:
> 
>    1. Ligand restraints editing with REEL (Joseph Brock)
>    2. Re: Ligand restraints editing with REEL (Ralf W. Grosse-Kunstleve)
>    3. Resolve NCS masks (Florian Schmitzberger)
> 
> 
> ----------------------------------------------------------------------
> 
> Message: 1
> Date: Sat, 18 Sep 2010 08:09:23 +0000
> From: Joseph Brock <joeylives2ride at hotmail.com>
> To: <phenixbb at phenix-online.org>
> Subject: [phenixbb] Ligand restraints editing with REEL
> Message-ID: <SNT120-W580E16EA4DC524ED59A3209B7C0 at phx.gbl>
> Content-Type: text/plain; charset="iso-8859-1"
> 
> 
> Hi all,
> 
> I'm working on a 1.5A structure that contains a novel ligand within the active site, which is an Arsenic derivative of Glutathione, using the Phenix GUI, version 1.6.4-486. 
> 
> I have been using the 'Molinspiration' webpage (http://www.molinspiration.com/docu/webme/) to generate a smiles string, which I then feed into ELBOW. Although the structure/chemical restraints of Glutathione should be unchanged by the covalent linkage to arsenic through the cysteinyl sulfur, the resulting restraints file consistently restricts one of the dihedrals to a value that is incompatible with the (quite clear) electron density. This occurs regardless of wether i use AM1 optimization, and is unresponsive to using native Glutathione (which refines into the corresponding density extremely well) as an input geometry file with any of the available 'Use geometry for' options (final geometry, initial geometry, etc).
> 
> I then tried opening the output file in REEL and manually changing the corresponding dihedrals to those of glutathione, however after running simple optimization, the resulting restraints file has the same problem, and upon choosing the 'transer geometry and restraints' option (or any option) midway through running the 'eLBOW optimization' or 'AM1 optimization' options, Phenix consistently crashes.
> 
> Any advice on how to transfer the origional geometry of native Glutathione to my new ligand effectively would be greatly appreciated. I'm a little confused as to the abilities of REEL, and how to affect them.
> 
> Thanks so much in advance.
> 
> Cheers,
> 
> -Joe.
> 
>  		 	   		  
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> ------------------------------
> 
> Message: 2
> Date: Sat, 18 Sep 2010 08:13:41 -0700 (PDT)
> From: "Ralf W. Grosse-Kunstleve" <rwgk at yahoo.com>
> To: PHENIX user mailing list <phenixbb at phenix-online.org>
> Subject: Re: [phenixbb] Ligand restraints editing with REEL
> Message-ID: <822193.92122.qm at web111407.mail.gq1.yahoo.com>
> Content-Type: text/plain; charset="us-ascii"
> 
> Hi Joe,
> Nigel who wrote elbow+reel is traveling so I'll try to help until he gets a 
> chance to respond.
> I very simple suggestion is do manually edit the cif file generated by elbow 
> before you
> pass it to phenix.refine; The cif file format is meant to be human-readable.
> Another option is to modify the dihedral definitions in reel and to save the 
> file without
> running the elbow optimizations again. There is nothing wrong with overriding 
> the
> elbow results with your chemical knowledge.
> A third idea is to run elbow with the Glutathione from your PDB file as the 
> input, instead
> of using the smiles string. That may give elbow a better start.
> If phenix.refine rejects your inputs I'd be interested to see the log file with 
> the error messages.
> If you send me the Glutathione residue from your PDB file (directly; not to 
> list) I could help more.
> Ralf
> 
> 
> 
> 
> 
> ________________________________
> From: Joseph Brock <joeylives2ride at hotmail.com>
> To: phenixbb at phenix-online.org
> Sent: Sat, September 18, 2010 1:09:23 AM
> Subject: [phenixbb] Ligand restraints editing with REEL
> 
>  Hi all,
> 
> I'm working on a 1.5A structure that contains a novel ligand within the active 
> site, which is an Arsenic derivative of Glutathione, using the Phenix GUI, 
> version 1.6.4-486. 
> 
> 
> I have been using the 'Molinspiration' webpage 
> (http://www.molinspiration.com/docu/webme/) to generate a smiles string, which I 
> then feed into ELBOW. Although the structure/chemical restraints of Glutathione 
> should be unchanged by the covalent linkage to arsenic through the cysteinyl 
> sulfur, the resulting restraints file consistently restricts one of the 
> dihedrals to a value that is incompatible with the (quite clear) electron 
> density. This occurs regardless of wether i use AM1 optimization, and is 
> unresponsive to using native Glutathione (which refines into the corresponding 
> density extremely well) as an input geometry file with any of the available 'Use 
> geometry for' options (final geometry, initial geometry, etc).
> 
> I then tried opening the output file in REEL and manually changing the 
> corresponding dihedrals to those of glutathione, however after running simple 
> optimization, the resulting restraints file has the same problem, and upon 
> choosing the 'transer geometry and restraints' option (or any option) midway 
> through running the 'eLBOW optimization' or 'AM1 optimization' options, Phenix 
> consistently crashes.
> 
> Any advice on how to transfer the origional geometry of native Glutathione to my 
> new ligand effectively would be greatly appreciated. I'm a little confused as to 
> the abilities of REEL, and how to affect them.
> 
> Thanks so much in advance.
> 
> Cheers,
> 
> -Joe.
> -------------- next part --------------
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> 
> ------------------------------
> 
> Message: 3
> Date: Sat, 18 Sep 2010 13:34:38 -0400
> From: Florian Schmitzberger <schmitzberger at crystal.harvard.edu>
> To: PHENIX user mailing list <phenixbb at phenix-online.org>
> Subject: [phenixbb] Resolve NCS masks
> Message-ID: <2763CBC2-38E8-4874-9039-4537BE2A5B61 at crystal.harvard.edu>
> Content-Type: text/plain; charset=US-ASCII; format=flowed; delsp=yes
> 
> Dear All,
> 
> I would have a question regarding the use of masks in Resolve in  
> Phenix for density modification:
> 
> Is it possible to output the NCS and/or solvent masks Resolve is using  
> during the Autosol run (similar as the options from the stand alone  
> Resolve version) such as:
> mask_as_mtz
> ncs_mask_file mask.mtz
> protein_mask_file
> 
> What are the best criteria (other than the final maps of course)  
> within the output from Phenix.resolve to judge if the NCS (and/or  
> solvent) mask was chosen adequately? (NCS_overlap?) I am mostly  
> concerned if the masks chosen do include some of the more peripheral  
> parts of my protein molecule and do not flatten these regions.
> 
> Secondly, it is possible within Phenix Autosol wizard to supply a pdb  
> file (with dummy atoms) for the mask for Resolve to construct the NCS  
> mask?
> i.e. similar to
> set mask_pdb file= dummyatom.pdb
> 
> Regards,
> 
> Florian
> 
> -----------------------------------------------------------
> Florian Schmitzberger
> Biological Chemistry and Molecular Pharmacology
> Harvard Medical School
> 250 Longwood Avenue, SGM 130
> Boston, MA 02115, US
> Tel: 001 617 432 5602
> 
> 
> 
> 
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