Re: SMD with different pH

From: Brian Bennion (brian_at_youkai.llnl.gov)
Date: Wed Mar 10 2004 - 10:47:37 CST

Hello Volodya,

You don't have to calculate the pka for every single residue in the
protein. In fact since histidine residues are probably the only amino
acids to change protonation state in the pH range you listed (6-7.5) just
isolate those that have access to a proton donor or acceptor.

I some special cases other residues might have a non standard protonation
state due to it unique local environment.

If you really need some numbers you can cut an area out of protein and
just run calculations on that section. GAMESS is free and lots of people
use it on windows/linux/cygwin

Otherwise the gross approximation method I mentioned earlier is your best
bet....

Brian

On Wed, 10 Mar 2004, Volodymyr Nechiporuk-Zloy wrote:

>
> Dear Brian,
>
> Thank you very much for your suggestions. I spoke with a specialist from
> Cosmologic about COSMO-RS. As I understand, I can try to calculate the pKa
> of the amino acids in my protein by semi empirical methods. The academic
> license is near 3000 + 3000 euro. It is expensive for me. Also the
> calculation's for so large molecules (my protein is near 100 kDa) are not
> established.
> Can you propose mesome other ways? Other software?
>
> Volodya
>
>
> On Fri, 5 Mar 2004, Brian Bennion wrote:
>
> >
> > Hello Volodya
> > You have just struck on one of the most thought about problems in
> > classical computational chemistry. As long as you are in the classical
> > regime you will never know what the solution pH is, because
> > water never forms its equilibrium with OH- and H30+.
> > Having said that, some people will make a very gross approximation and
> > assign pH by changing the protonation state of various amino acids. But
> > unless you have titration data from NMR experiments you still don't know
> > which histidines are protonated in your case.
> >
> > A semi empirical package called COSMO-RS is as about as close you can get
> > without going full ab initio to determine protonation states.
> >
> >
> >
> > On Fri, 5 Mar 2004, Volodymyr Nechiporuk-Zloy wrote:
> >
> > > Dear NAMD users,
> > >
> > > I want to model the unbinding of a peptide from a protein with
> > > different pH (6.0-7.5). How can I perform this? How can I note the pH of
> > > solution in the model. I want to use namd2 (SMD). I can also use other
> > > packages of programs. Any suggestions will be lelpfully.
> > >
> > > Sincerely your,
> > >
> > > Volodya
> > >
> >
> > *****************************************************************
> > **Brian Bennion, Ph.D. **
> > **Computational and Systems Biology Division **
> > **Biology and Biotechnology Research Program **
> > **Lawrence Livermore National Laboratory **
> > **P.O. Box 808, L-448 bennion1_at_llnl.gov **
> > **7000 East Avenue phone: (925) 422-5722 **
> > **Livermore, CA 94550 fax: (925) 424-6605 **
> > *****************************************************************
> >
> >
>

*****************************************************************
**Brian Bennion, Ph.D. **
**Computational and Systems Biology Division **
**Biology and Biotechnology Research Program **
**Lawrence Livermore National Laboratory **
**P.O. Box 808, L-448 bennion1_at_llnl.gov **
**7000 East Avenue phone: (925) 422-5722 **
**Livermore, CA 94550 fax: (925) 424-6605 **
*****************************************************************

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