Hi all,<br><br>It's really a transition state of enzyme catalyzed reaction as Tsjerk said. Firstly, the hydrogen from serine will bind with the His nearby. Afterwards, the serine residue will nucleophilicly bind with substrate to form such a tetrahedral intermediate.<br>
However, i did not attend to explore the whole catalysis process by molecular dynamics simulation. Acturally, i expect to get such a system stable in transition state. After the equilirium of the system, i can change the position of some groups of substrate. At this moment, the substrate can be changed to another conformation--another enantiomer, and the free energy difference between two state is expected to be calculated by thermodynamic intergration. By this way, the tendency of the system changing from one state to another one can be parameterized.<br>
So I guess the biggest trouble i encountered might be the construction of such a transition state system and let it run in Gromacs. But I can't work with force field parameter as Justin said. Maybe i should take the feasibility of my original plan into a good consideration. Anyway, so much thanks to you guys. Mark, Tsjerk, Justin and everyone here.<br>
<br>Regards<br>Ji <br><br><div class="gmail_quote">On Thu, Feb 19, 2009 at 8:43 PM, Tsjerk Wassenaar <span dir="ltr"><<a href="mailto:tsjerkw@gmail.com">tsjerkw@gmail.com</a>></span> wrote:<br><blockquote class="gmail_quote" style="border-left: 1px solid rgb(204, 204, 204); margin: 0pt 0pt 0pt 0.8ex; padding-left: 1ex;">
Hi,<br>
<br>
Even worse, this looks like a transition-state product. The hydrogen<br>
originating from the serine will not just have wandered off. It is<br>
unlikely that it happened to go sit on the other oxygen. Rather, the<br>
other oxygen, which would originally be double-bonded would probably<br>
form a strong hydrogen bond with some other residue (histidine?),<br>
rendering the carbon exposed enough for a nucleophilic attack by<br>
serine, followed by a series of events likely resulting in HO-R' being<br>
cut off. You won't be able to properly describe the transition state<br>
using classical means only.<br>
<br>
Cheers,<br>
<font color="#888888"><br>
Tsjerk<br>
</font><div><div></div><div class="Wj3C7c"><br>
On Thu, Feb 19, 2009 at 1:19 PM, Justin A. Lemkul <<a href="mailto:jalemkul@vt.edu">jalemkul@vt.edu</a>> wrote:<br>
><br>
><br>
> Ji Liu wrote:<br>
>><br>
>> Hi Tsjerk,<br>
>><br>
>> Sorry i did not supply any information about the enzyme/substrate system.<br>
>> Here, I'm studying the interaction between ester (substrate) and lipase<br>
>> (enzyme). The substrate contains C, O and H atoms. More details are shown in<br>
>> the following address.<br>
>> <a href="http://picasaweb.google.com/ZJULiuJi/Experiments#5304476447992943186" target="_blank">http://picasaweb.google.com/ZJULiuJi/Experiments#5304476447992943186</a><br>
>> Also I'll check the archives for related topics. Thank you so much.<br>
>><br>
><br>
> Based on the structure you've shown, I do not believe there is any easy<br>
> solution, other than going through the painstaking progress of deriving new<br>
> force field parameters. It doesn't matter so much which atom types are used<br>
> in your case, but how they are linked. An ester adduct such as you've shown<br>
> has not been parameterized within the Gromacs implementation of Gromos96.<br>
> If other researchers have done it, then your best bet is to see how they<br>
> did it and hopefully apply it to your situation.<br>
><br>
> Otherwise, you have a long project ahead of you just to derive the correct<br>
> parameters.<br>
><br>
> -Justin<br>
><br>
>> Ji<br>
>><br>
>> On Thu, Feb 19, 2009 at 6:18 PM, Tsjerk Wassenaar <<a href="mailto:tsjerkw@gmail.com">tsjerkw@gmail.com</a><br>
>> <mailto:<a href="mailto:tsjerkw@gmail.com">tsjerkw@gmail.com</a>>> wrote:<br>
>><br>
>> Hi Ji,<br>
>><br>
>> Well, if others have been there before, you can of course take from<br>
>> their experience. You haven't mentioned the substrate you're dealing<br>
>> with, though, so none of us can tell if we can offer the solution to<br>
>> your problem. First try to search the user list archives and the<br>
>> topology contribution section of the gromacs site. If that doesn't<br>
>> give any results, you can post to the user list and see if any of us<br>
>> has already been there...<br>
>><br>
>> Cheers,<br>
>><br>
>> Tsjerk<br>
>><br>
>><br>
>> On Thu, Feb 19, 2009 at 10:35 AM, Ji Liu <<a href="mailto:zjuliuji@gmail.com">zjuliuji@gmail.com</a><br>
>> <mailto:<a href="mailto:zjuliuji@gmail.com">zjuliuji@gmail.com</a>>> wrote:<br>
>> > Hi Tsjerk,<br>
>> ><br>
>> > Thanks a lot.<br>
>> > Surely I can't modify the force field by my self. It's impossible<br>
>> to me to<br>
>> > understand all of things you mentioned. So is it the only way to<br>
>> achieve my<br>
>> > purpose? If so, it's so frustrating. I've been trying my best to<br>
>> contact<br>
>> > with the author of one of my references. He applied several of<br>
>> Gromos 96<br>
>> > force field (may be he modified these force field too) to a similar<br>
>> > enzyme/substrate system, and hope i can get some information from<br>
>> him. Even<br>
>> > though, i really eager to get some knowledge from all of<br>
>> gmx-users. Anyway,<br>
>> > I'm always grateful for your comment.<br>
>> ><br>
>> > Ji<br>
>> > On Thu, Feb 19, 2009 at 5:09 PM, Tsjerk Wassenaar<br>
>> <<a href="mailto:tsjerkw@gmail.com">tsjerkw@gmail.com</a> <mailto:<a href="mailto:tsjerkw@gmail.com">tsjerkw@gmail.com</a>>> wrote:<br>
>> >><br>
>> >> Hi,<br>
>> >><br>
>> >> > I'm not familiar with<br>
>> >> > i can't tell myself which<br>
>> >> > guess i can<br>
>> >> > I have no idea whether<br>
>> >><br>
>> >> This is the worst possible basis for trying to modify a force<br>
>> field.<br>
>> >> First get well acquainted with molecular dynamics and the role and<br>
>> >> whereabouts of force fields. Then you can start thinking of<br>
>> using such<br>
>> >> knowledge to modify the force field. You will possibly be able to<br>
>> >> change a force field, but making it produce sensible results is a<br>
>> >> different thing.<br>
>> >><br>
>> >> Sorry for not telling you what you want to hear.<br>
>> >><br>
>> >> Tsjerk<br>
>> >><br>
>> >> --<br>
>> >> Tsjerk A. Wassenaar, Ph.D.<br>
>> >> Junior UD (post-doc)<br>
>> >> Biomolecular NMR, Bijvoet Center<br>
>> >> Utrecht University<br>
>> >> Padualaan 8<br>
>> >> 3584 CH Utrecht<br>
>> >> The Netherlands<br>
>> >> P: +31-30-2539931<br>
>> >> F: +31-30-2537623<br>
>> >> _______________________________________________<br>
>> >> gmx-users mailing list <a href="mailto:gmx-users@gromacs.org">gmx-users@gromacs.org</a><br>
>> <mailto:<a href="mailto:gmx-users@gromacs.org">gmx-users@gromacs.org</a>><br>
>> >> <a href="http://www.gromacs.org/mailman/listinfo/gmx-users" target="_blank">http://www.gromacs.org/mailman/listinfo/gmx-users</a><br>
>> >> Please search the archive at <a href="http://www.gromacs.org/search" target="_blank">http://www.gromacs.org/search</a><br>
>> before posting!<br>
>> >> Please don't post (un)subscribe requests to the list. Use the<br>
>> >> www interface or send it to <a href="mailto:gmx-users-request@gromacs.org">gmx-users-request@gromacs.org</a><br>
>> <mailto:<a href="mailto:gmx-users-request@gromacs.org">gmx-users-request@gromacs.org</a>>.<br>
>> >> Can't post? Read <a href="http://www.gromacs.org/mailing_lists/users.php" target="_blank">http://www.gromacs.org/mailing_lists/users.php</a><br>
>> ><br>
>> ><br>
>> > _______________________________________________<br>
>> > gmx-users mailing list <a href="mailto:gmx-users@gromacs.org">gmx-users@gromacs.org</a><br>
>> <mailto:<a href="mailto:gmx-users@gromacs.org">gmx-users@gromacs.org</a>><br>
>> > <a href="http://www.gromacs.org/mailman/listinfo/gmx-users" target="_blank">http://www.gromacs.org/mailman/listinfo/gmx-users</a><br>
>> > Please search the archive at <a href="http://www.gromacs.org/search" target="_blank">http://www.gromacs.org/search</a> before<br>
>> posting!<br>
>> > Please don't post (un)subscribe requests to the list. Use the<br>
>> > www interface or send it to <a href="mailto:gmx-users-request@gromacs.org">gmx-users-request@gromacs.org</a><br>
>> <mailto:<a href="mailto:gmx-users-request@gromacs.org">gmx-users-request@gromacs.org</a>>.<br>
>> > Can't post? Read <a href="http://www.gromacs.org/mailing_lists/users.php" target="_blank">http://www.gromacs.org/mailing_lists/users.php</a><br>
>> ><br>
>><br>
>><br>
>><br>
>> --<br>
>> Tsjerk A. Wassenaar, Ph.D.<br>
>> Junior UD (post-doc)<br>
>> Biomolecular NMR, Bijvoet Center<br>
>> Utrecht University<br>
>> Padualaan 8<br>
>> 3584 CH Utrecht<br>
>> The Netherlands<br>
>> P: +31-30-2539931<br>
>> F: +31-30-2537623<br>
>> _______________________________________________<br>
>> gmx-users mailing list <a href="mailto:gmx-users@gromacs.org">gmx-users@gromacs.org</a><br>
>> <mailto:<a href="mailto:gmx-users@gromacs.org">gmx-users@gromacs.org</a>><br>
>> <a href="http://www.gromacs.org/mailman/listinfo/gmx-users" target="_blank">http://www.gromacs.org/mailman/listinfo/gmx-users</a><br>
>> Please search the archive at <a href="http://www.gromacs.org/search" target="_blank">http://www.gromacs.org/search</a> before<br>
>> posting!<br>
>> Please don't post (un)subscribe requests to the list. Use the<br>
>> www interface or send it to <a href="mailto:gmx-users-request@gromacs.org">gmx-users-request@gromacs.org</a><br>
>> <mailto:<a href="mailto:gmx-users-request@gromacs.org">gmx-users-request@gromacs.org</a>>.<br>
>> Can't post? Read <a href="http://www.gromacs.org/mailing_lists/users.php" target="_blank">http://www.gromacs.org/mailing_lists/users.php</a><br>
>><br>
>><br>
>><br>
>> ------------------------------------------------------------------------<br>
>><br>
>> _______________________________________________<br>
>> gmx-users mailing list <a href="mailto:gmx-users@gromacs.org">gmx-users@gromacs.org</a><br>
>> <a href="http://www.gromacs.org/mailman/listinfo/gmx-users" target="_blank">http://www.gromacs.org/mailman/listinfo/gmx-users</a><br>
>> Please search the archive at <a href="http://www.gromacs.org/search" target="_blank">http://www.gromacs.org/search</a> before posting!<br>
>> Please don't post (un)subscribe requests to the list. Use the www<br>
>> interface or send it to <a href="mailto:gmx-users-request@gromacs.org">gmx-users-request@gromacs.org</a>.<br>
>> Can't post? Read <a href="http://www.gromacs.org/mailing_lists/users.php" target="_blank">http://www.gromacs.org/mailing_lists/users.php</a><br>
><br>
> --<br>
> ========================================<br>
><br>
> Justin A. Lemkul<br>
> Graduate Research Assistant<br>
> Department of Biochemistry<br>
> Virginia Tech<br>
> Blacksburg, VA<br>
> jalemkul[at]<a href="http://vt.edu" target="_blank">vt.edu</a> | (540) 231-9080<br>
> <a href="http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin" target="_blank">http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin</a><br>
><br>
> ========================================<br>
> _______________________________________________<br>
> gmx-users mailing list <a href="mailto:gmx-users@gromacs.org">gmx-users@gromacs.org</a><br>
> <a href="http://www.gromacs.org/mailman/listinfo/gmx-users" target="_blank">http://www.gromacs.org/mailman/listinfo/gmx-users</a><br>
> Please search the archive at <a href="http://www.gromacs.org/search" target="_blank">http://www.gromacs.org/search</a> before posting!<br>
> Please don't post (un)subscribe requests to the list. Use the www interface<br>
> or send it to <a href="mailto:gmx-users-request@gromacs.org">gmx-users-request@gromacs.org</a>.<br>
> Can't post? Read <a href="http://www.gromacs.org/mailing_lists/users.php" target="_blank">http://www.gromacs.org/mailing_lists/users.php</a><br>
><br>
<br>
<br>
<br>
</div></div>--<br>
<div class="Ih2E3d">Tsjerk A. Wassenaar, Ph.D.<br>
Junior UD (post-doc)<br>
Biomolecular NMR, Bijvoet Center<br>
Utrecht University<br>
Padualaan 8<br>
3584 CH Utrecht<br>
The Netherlands<br>
P: +31-30-2539931<br>
F: +31-30-2537623<br>
_______________________________________________<br>
gmx-users mailing list <a href="mailto:gmx-users@gromacs.org">gmx-users@gromacs.org</a><br>
</div><div><div></div><div class="Wj3C7c"><a href="http://www.gromacs.org/mailman/listinfo/gmx-users" target="_blank">http://www.gromacs.org/mailman/listinfo/gmx-users</a><br>
Please search the archive at <a href="http://www.gromacs.org/search" target="_blank">http://www.gromacs.org/search</a> before posting!<br>
Please don't post (un)subscribe requests to the list. Use the<br>
www interface or send it to <a href="mailto:gmx-users-request@gromacs.org">gmx-users-request@gromacs.org</a>.<br>
Can't post? Read <a href="http://www.gromacs.org/mailing_lists/users.php" target="_blank">http://www.gromacs.org/mailing_lists/users.php</a><br>
</div></div></blockquote></div><br>