- modeller_usage - salilab.org

Re: [modeller_usage] OBJECTIVE FUNCTION
by Matthias 30 Mar '04

30 Mar '04

Thanks a lot, i appreciated your help..

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Adding ligand in protein will solve sidechain confromatin problem?
by Nataraj Balkrishnan 30 Mar '04

30 Mar '04

Dear Modeller, I modelled a protein from low identies template,and more I am having the idea of location of active site for my modelled protien for particular ligands. Since I know the active site of the model, I want to construct the sidechain of aminoacids involved in that active site,by adding ligand in that particular location.(Since I belive that the configuration of sidechain in the state of interaction with ligand would be the actual conformation of the sidechains of active site). Now my questions are 1)Wheather my this idea is theoreticaly correct ? 2)if the answer for my question 1 is correct, what is the way or routine which I can use it for adding my ligand(small molecule,eg.,DDT) to my model? Kindly help me... Thank you in advance. Yours truly, B.Nataraj --------------------------------- Yahoo! Messenger - Communicate instantly..."Ping" your friends today! Download Messenger Now

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Can any get Z-score for my target sequence in PROSAII?
by Nataraj Balkrishnan 30 Mar '04

30 Mar '04

Dear Modeller, Sorry I don't know ,wheater It is ethical to ask as such help from your end. But I am helpless. I have modelled a protein in modeller from a low identiy template with respect to my target. I checked my internal verification of my model and external too ,such as PROCHEK ,whatchek etc., But PROSAII is one test that I have not attempted since I don't have that software. If any volunteers out there having PROSAII software, may help me to predict data (Z score or more) for my target protein. If any body willing please mail me up and send my coordinate to you. With regards, B.Nataraj --------------------------------- Yahoo! Messenger - Communicate instantly..."Ping" your friends today! Download Messenger Now

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Re: [modeller_usage] Adding ligand in protein will solve sidechainconfromatin problem?
by Eric Feyfant 29 Mar '04

29 Mar '04

Dear Nataraj; 1/ Theoretically, yes it seems valid but you will be confronted to several issues. 2 main ones could be: a/ You have to see if the active site is more conserved that the overall protein, don't expect to bind correctly a ligand in a pocket that share a low identity with your template (it also depends on your definition of low identity!). For example, in a case of Kinase, it is common to have low identity between the kinase (overall of 30-40%) but the ATP binding site, which is very often targeted in drug design, share a much higher identity (70 to 80%). b/ If your active site identity is not that an issue, you may need rearrangement of the side chain in order to bind correctly the ligand. But Modeller derived homology restraint from the template which doesn't have the ligand (I presume), therefore these restraints may become a problem for your optimization, especially side chain - side chain restraints. In that case I will suggest you 2 approaches: - you can delete the side chain - side chain restraints for the active site. - Build you model without the ligand and dock it after using a docking software. Now if you template as the same ligand bound into it and you have just some mutation in your active site therefor: Yes you can use your idea. And to add a small ligand check the FAQs on the manual, you will find some answers. Good luck! Eric ------------------------------------ Eric Feyfant, Ph.D. Senior research Scientist Computational Chemistry Wyeth Research 200 Cambridge Park Drive Cambridge, MA 02140 tel: +1 617 665 5656 fax: +1 617 665 5682 email: efeyfant(a)wyeth.com >>> Nataraj Balkrishnan <natarajmtech(a)yahoo.co.uk> 3/29/2004 1:11:10 PM >>> Dear Modeller, I modelled a protein from low identies template,and more I am having the idea of location of active site for my modelled protien for particular ligands. Since I know the active site of the model, I want to construct the sidechain of aminoacids involved in that active site,by adding ligand in that particular location.(Since I belive that the configuration of sidechain in the state of interaction with ligand would be the actual conformation of the sidechains of active site). Now my questions are 1)Wheather my this idea is theoreticaly correct ? 2)if the answer for my question 1 is correct, what is the way or routine which I can use it for adding my ligand(small molecule,eg.,DDT) to my model? Kindly help me... Thank you in advance. Yours truly, B.Nataraj Yahoo! Messenger - Communicate instantly..."Ping" your friends today! Download Messenger Now

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The selection of models
by Binbin Liu 29 Mar '04

29 Mar '04

Dear Modellers, 100 models were generated based on one template. Their atomic RMSDs all are less than 0.4 Angstroms. Does any body know any other way I can find a representative model from the 100 models. Many thanks. Binbin

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modeller errors
by kambhampati anjaneyulu 28 Mar '04

28 Mar '04

Respected sir ; how to run the programme in windows xp sysytem . which commnand i have to use .and how to run the programme.please clarify my doubts --------------------------------- Do you Yahoo!? Yahoo! Finance Tax Center - File online. File on time.

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Re: [modeller_usage] side-chain torsion angles
by Eric Feyfant 26 Mar '04

26 Mar '04

Hi Liu; I just want to add a comment to what Mickael just told you. Basically, Modeller use spatial restraint derived from the homology, which means that it will derive the restraint for the side chain from the residues in the template with which is aligned. Modeller has a table for equivalent position between residues: example Alanine and Lysine will share as equivalent backbone atoms and the Calpha . This means that if your template is Ala and your target is Lysine, only homology restraint concerning backbone + Calpha will be derived from the Ala and applied to the Lysine. That implies that your Lysine side chain will be optimize with non homology derived restraints (i.e. those from template),and so more dependent on the starting conformation, the environment and, the potential your are using. At the opposite if you check the identical residues you should see less fluctuation. Best Eric. >>> Mickael Krzeminski <mkrzemin(a)pasteur.fr> 3/26/2004 6:23:57 AM >>> Liu, Your problem deals essentially with side chains. You have to know that all programs of homology modeling have difficulties for prediction of side chains and results are often bad... Basically, at the biginning, programs choose conformation of side chains of templates in conditon that the same residuse are aligned. If it is not the case, the side chain is placed and is minimized. So, it is logical whether your side chains are different between your models because the minimization depends on the local environnement. I hope you have understood what i had tried to explain... With regards, Mickaël On Wed, 24 Mar 2004, Binbin Liu wrote: > Hi there, > I got one hunderd models. The side-chain torsion angles of the interesting > residues are vary. Does anybody know why. Does MODELLER calculate the torsion > based on some rules or it is by chance. > > > Cheers > > > BinBin > _______________________________________________ > modeller_usage mailing list > modeller_usage(a)salilab.org > http://salilab.org/mailman/listinfo/modeller_usage > _______________________________________________ modeller_usage mailing list modeller_usage(a)salilab.org http://salilab.org/mailman/listinfo/modeller_usage

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side-chain torsion angles
by Binbin Liu 26 Mar '04

26 Mar '04

Hi there, I got one hunderd models. The side-chain torsion angles of the interesting residues are vary. Does anybody know why. Does MODELLER calculate the torsion based on some rules or it is by chance. Cheers BinBin

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OBJECTIVE FUNCTION
by Matthias 26 Mar '04

26 Mar '04

-- NeoMail - Webmail that doesn't suck... as much. I took several runs on Modeller and gaint 2 models.Further I otpimized these models by loop modelling and this final loop models present a very low, regarding to the other, OBJECTIVCE FUNCTION. But, my question: is this objective function relates only to the loop models or is it a value for the global model? Further: does anybody know if there should be great differences in performin a modeller job in one or two top scripts.. it seems to work better when splitted, why? Thxs a lot , Matthias Negri Diploma student

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Number problem
by hemant kushwaha 24 Mar '04

24 Mar '04

Dear sir, I am trying to model a allosteric protein, my problem is that the number of residues in alignment file(with template and target sequence) and pdb file is different b'cos in PDB file there is a gap in the atoms and HETATM. So modeller is giving error at check alignment, and giving no. of residues in alignment and pdb file are different. Can you please give me any suggestion or advice how to sort this problem with regards Hemant __________________________________ Do you Yahoo!? Yahoo! Finance Tax Center - File online. File on time. http://taxes.yahoo.com/filing.html

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