Hi Alicia, Ben: Thanks for your reply, which help me a lot. But for my specific situation, the ligand I am trying to use is phenacetin which did not exist in the template pdb file. Or to say, we created it so as to make it docked in the active site by using some NMR restraints. We expected to see some interactions between the ligand and the active site which will make the active site show a differnt look from what it is when no ligand is bound. Now I was really confused, if the ligand can not have correct connectivity, how can we expect to see the interactions between the ligand and the enzyme? I mean how the follwong refinement steps which is involved with minimization and molecular dynamics correctly dealt with the ligand and the interaction between the ligand and the enzyme? Again, why the ligand does not show correctly, you know , we build the phenacetin in Builder module in InsightII and output it as a RTF file, then append it to the top_heav.lib file. The molecule looks very reasonable in InsightII, but after calculation by MODELLER , the ligand looked weird. So, any other program can view RTF file so as to have a check the connectivity of the ligand is reasonably good or not? Or if the parameters are incomplete, how to make it complete? Another question is whether does the RTF file provide enough connectivity information for the ligand? Or is it because of the special restraints we applied in MODELLER which make the connectivity changed? You know,we even tried to use the ligand without any restraints, the result still looked weird? Basically, we just want to build a new ligand with some experimental restraints in the active site of a enzyme. If the ligand looked werid, we have to doubt whether the interaction between the ligand and the enzyme is reliable or not? So, we have to know which step create this problem? 1. building the ligand (RFT file)? We did not give enough connectivity information? 2. running MODELLER? Since there is no restraints to confine the bond or angles for the ligand or the restraints are conflicting with each other which make the ligand broken? 3. outputting file from MODELLER? Assumed that all the above is good, the only problem is that MODDLER only give the cooridinates of the atoms instead of the relationship ( connectivity) between atoms? Hope I have well explained my problems? And I also attached my RTF file for phenacetin. Finally, thanks for your guys' kind help. Anyone's reply in this topic will be highly appreciated. Hope for the best.

youbin

Higueruelo Alicia (CAM) wrote:

>Hi Youbin, > >In my experience,(please someone correct me if I'm wrong) the ligands in >modeller don't look great, my guess is that CHARMm deals really well with >aminoacids but struggle a bit with non-aminoacid atom types. (or a least the >version I'm using). > >But they look reasonable. If the ligand look really really weird. try to >compare the "PDB atom names" in your template ( the pdb file you are using >to built your model) and the "PDB atom names" in your top_heavy.lib. Hope >the following lines are a good example. > >in top_heav.lib in RESI LIG "ATOM O1 OE -0.10000" >in template.pdb "ATOM 4000 O1 LIG D 500 30.722 47.505 16.832" > >To have the same connection and geometry in the model-ligand than in the >ligand-template, these PDB names should be the same "O1", I think this is >what is telling Modeller where to put the atom (assigning the xyz coords >from atom called O1 from the LIG in the PDB), and "OE" is the CHARMm atom >type to use the potentials . > >In my output files, my model does not have connection data in the pdb, >therefore the way you see you models depends which software you are using to >visualize your pdb, again, lots of them can not guess that a phenyl ring >(not in a aminoacid) has alternate double bounds or aromatic bonds, and >display them in funny ways. There are spl macros in sybyl for example, which >will fix some of these problems, based on the geometry of the ligands. but >I'm not aware of a 3D viewer which display chemically correctly all ligands >in pdb format. > >Hope this is useful, > >any comments on that more than welcome, > >cheers, > >alicia > > >-----Original Message----- >From: Youbin Tu [mailto:ytu@mix.wvu.edu] >Sent: 16 November 2004 07:08 >To: modeller_usage@salilab.org >Subject: [modeller_usage] wrong topology for the ligand? > > >Hi all: > > I am using MODELLER7V7 to build a ligand-enzyme complex, I created >the ligand and modified the library files. Everything worked well >except the ligand in the final result seems too weird, for example the >benzene is not planar and there are many bonds between 2 atoms which >should only have one bond theoritically. > I thought maybe it is my problem when building the ligand. But >when I tried to use GDP which already existed in the library file. The >final >results still have the same problem. > Anyone knows how to deal with this kind of problem? Does it mean >that we have to modify the par.lib or make restraints for bonds of the >ligands? If so, can you tell me how to do that,any softwares are >available for that purpose? > Your reply is highly appreciated. > > >youbin > > > > > >_______________________________________________ >modeller_usage mailing list >modeller_usage@salilab.org >http://salilab.org/mailman/listinfo/modeller_usage > > >The information contained in this email is intended for the >personal and confidential use of the addressee only. It may >also be privileged information. If you are not the intended >recipient then you are hereby notified that you have received >this document in error and that any review, distribution or >copying of this document is strictly prohibited. If you have >received this communication in error, please notify Celltech >immediately on: >+44 (0)1753 534655, or email 'is@celltech.co.uk' >Celltech Group plc >208 Bath Road, Slough, SL1 3WE, Berkshire, UK >Registered Office as above. > >

---------------------- Youbin Tu CCMM Lab,BPS Schoof of Pharmacy,WVU