Re: Hi: Re: [gmx-users] Hello: Forcefield and potentials for DNA-zinc finger complex
Hi Nehme, Also, in our zinc finger models, the zinc plays a structural role and it is not implicated in DNA recognition. Furthermore, I will read your paper and the references. I looked in the Literature and from NMR studies/X-ray and MD done on zinc fingers containing a zinc ion coordinated to 4 cysteines. It seems that these cysteines are deprotonated and the remaining negative charges are stabilized by nearby positively charged side chains of arginines or lysines. It's hard, although not impossible, to assess the protonation state of such a center experimentally. Mind that crystal structures and NMR structures also use force fields and predefined topologies to model the structure. That means that you will only get out what you put in. If you set some group to be deprotonated while it should be protonated, this may be hard or even impossible to track down. You may still get a reasonable fit to the experimental data. For such issues Xray/NMR are not the best means. Note that I'm not saying you're wrong, but you should justify your choices. I tried to use CHARMM forcefield, but every time I had the 4 cysteines protonated, the coordination bonds removed and the parameters for zinc not assigned. How can I solve this issue? In Gromacs you can use the file specbond.dat to define special bonds. Have a look at http://wiki.gromacs.org/index.php/specbond.dat and search the archives for more information. Cheers, Tsjerk -- Tsjerk A. Wassenaar, Ph.D. Junior UD (post-doc) Biomolecular NMR, Bijvoet Center Utrecht University Padualaan 8 3584 CH Utrecht The Netherlands P: +31-30-2539931 F: +31-30-2537623 ___ gmx-users mailing listgmx-users@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php
Re: Hi: Re: [gmx-users] Hello: Forcefield and potentials for DNA-zinc finger complex
Hi Nehme, I've did simulations on TRAIL, which also contains a zinc-finger domain, involving three cysteines and a chloride ion. But it's not so simple. Luckily the exact parameters seemed not that vital, as the zinc apparently functions to keep the three subunits together and was in any case not directly related to the properties we were interested in. Still, I spent some time parameterizing it. For that I did quite a search of the available literature. You'll find some references in our 2008 Proteins paper. One of the most striking things is the still unresolved issue of the protonation state of zinc finger domains. Especially in the acidic environment around DNA, this may become an issue. It is why I have stayed away from zinc-finger domains lately, as they'd cost me too much work properly parameterizing them, even though our lab is doing experimental work on them and it would be interesting to complement that with MD. That's also why I mentioned to be interested in such parameters. Not in what you can readily calculate with QM or what you can get from automatic topology builders or even from literature, including my own. That doesn't solve the issue of the protonation state or overall charge of the complex. I won't trust any report on zinc-finger domain MD, unless it is shown to properly reproduce experimental properties, including what can be determined in relation to the protonation state. Cheers, Tsjerk On Wed, May 20, 2009 at 10:40 AM, Nehme El Hachem n...@aub.edu.lb wrote: Hi Tsjerk, I thank you for your help. Indeed, I am very new to GROMACS ( I have a Linux Red hat 9.0 and I do have some issues installing the software). If you are interested, please find a link: http://www.epress.com/w3jbio/vol2/harris2/harris.htm Molecular Dynamics Simulation Of The Estrogen Receptor Protein In Complex With A Non-Consensus Estrogen Response Element DNA Sequence In A 10 Angstrom Water Layer. I am trying to do some molecular dynamics on the oestrogen receptor DNA binding domain (PDB code: 1HCQ). I have InsightII with Discover3 and CHARMm but I am confused with the type of forcefield that I need. Furthermore, I have to add counterions to neutralize the system, so it seems complicated. I wanted to try GROMACS, because it has many forcfields (ex: ffAmber) for modeling this type of system. I appreciate your help, Nehme. -- Tsjerk A. Wassenaar, Ph.D. Junior UD (post-doc) Biomolecular NMR, Bijvoet Center Utrecht University Padualaan 8 3584 CH Utrecht The Netherlands P: +31-30-2539931 F: +31-30-2537623 ___ gmx-users mailing listgmx-users@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php
[gmx-users] Hello: Forcefield and potentials for DNA-zinc finger complex
Hello, I have a DNA-Zinc finger complex. What are the suitable forcefields for that type of complexes (the zinc ion is coordinated to 4 deprotonated cysteines)? I need to do some molecular minimization and dynamics including the nucelic acid sequence. Looking for some help. Thank you. Nehme ___ gmx-users mailing listgmx-users@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php
Re: [gmx-users] Hello: Forcefield and potentials for DNA-zinc finger complex
Nehme El Hachem wrote: Hello, I have a DNA-Zinc finger complex. What are the suitable forcefields for that type of complexes (the zinc ion is coordinated to 4 deprotonated cysteines)? The first step is probably to search in the literature for anything similar. Has anyone attempted such work? Is there precedent for making the force field choice? The only force field I know of that contains deprotonated cysteine that has also been implemented in Gromacs is AMBER (residue CYM). The ffamber ports are available for download online. Another thing to consider is whether any MM force field will adequately describe your coordination complex, i.e.: http://wiki.gromacs.org/index.php/Exotic_Species -Justin I need to do some molecular minimization and dynamics including the nucelic acid sequence. Looking for some help. Thank you. Nehme ___ gmx-users mailing listgmx-users@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use thewww interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php -- Justin A. Lemkul Ph.D. Candidate ICTAS Doctoral Scholar Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin ___ gmx-users mailing listgmx-users@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php
Re: [gmx-users] Hello: Forcefield and potentials for DNA-zinc finger complex
Hi, Have a look at http://wiki.gromacs.org/index.php/Parameterization and http://wiki.gromacs.org/index.php/Exotic_Species Next to that, also consider that you are talking about a site with -2 formal charge (ZnS4)2-. How likely is that? From QM studies, it seems much more likely that there are 1 or 2 protons associated with the cluster. If you manage to model that properly, let me know; I'd be interested in that. Cheers, Tsjerk On Tue, May 19, 2009 at 2:01 PM, Nehme El Hachem n...@aub.edu.lb wrote: Hello, I have a DNA-Zinc finger complex. What are the suitable forcefields for that type of complexes (the zinc ion is coordinated to 4 deprotonated cysteines)? I need to do some molecular minimization and dynamics including the nucelic acid sequence. Looking for some help. Thank you. Nehme ___ gmx-users mailing list gmx-us...@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use thewww interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php -- Tsjerk A. Wassenaar, Ph.D. Junior UD (post-doc) Biomolecular NMR, Bijvoet Center Utrecht University Padualaan 8 3584 CH Utrecht The Netherlands P: +31-30-2539931 F: +31-30-2537623 ___ gmx-users mailing listgmx-users@gromacs.org http://www.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php
