Why not just run simulations of all 4 protonation states (if running
> constant pH is too much trouble)? That seems more defensible then just
> making up a protonation state based off some unrelated program.
>
> This is not possible for the following reasons:
* The protein is transmembrane and as far a I know AMBER12 does not support
implicit membrane simulations.
* Water molecules play a crucial role in ligand binding and transport,
therefore the implicit solvation is rejected.
* Conformational transitions in the transport cycle happen in the
milisecond time scale and hence I'm using aMD in NAMD (I have abundant CPU
time but AMBER is much slower that NAMD on CPUs). I
* It is not only the two residues in the binding pocket that are protonated.
>
>
> On Thu, Nov 14, 2013 at 3:14 PM, Thomas Evangelidis <tevang3.gmail.com
> >wrote:
>
> > Hi,
> >
> > calckpka read the output of constant pH MD, therefore is not useful in my
> > case. Is there any other third party tool I could use to find the
> > protonation of the binding pocket at a given pH value?
> >
> > thanks,
> > Thomas
> >
> >
> >
> > On 14 November 2013 21:50, Dwight McGee <dwight.mcgee.gmail.com> wrote:
> >
> > > Hi,
> > >
> > > I would take a look at the constant pH MD tutorial (
> > > http://ambermd.org/tutorials/advanced/tutorial18/). The program
> > > *calckpka* is
> > > used to analyze the results from constant pH MD simulations.
> > >
> > >
> > > On Thu, Nov 14, 2013 at 2:30 PM, Thomas Evangelidis <tevang3.gmail.com
> > > >wrote:
> > >
> > > > Dear AMBER community,
> > > >
> > > > I am simulating a protein-complex in which protonation of two
> glutamic
> > > > acids in the binding pocket is believed to dictate ligand binding and
> > > > release. I want to calculate pKa values from conformations along the
> > > > simulation and change if necessary the protonation of the protein by
> > also
> > > > taking into account the ligand. I used for this purpose PROPKA 3.1
> and
> > > H++
> > > > servers, but the results are contradictory. According to PROPKA 3.1
> the
> > > pKa
> > > > values of the two Glu residues in the starting conformation are 8.07
> > and
> > > > 7.61, therefore in pH 7.6 both will be protonated. According to the
> > > > titration curves produced by H++ these two residues are never
> > protonated
> > > at
> > > > pH 7.6 whatever dielectric I use for the protein (tried values 1-10).
> > It
> > > is
> > > > worth noting that the titration curve of the first Glu deviates a lot
> > > from
> > > > the Henderson-Hasselbalch curve.
> > > >
> > > > I am confused about what results I should trust. Is there a program
> in
> > > > AmberTools to calculate pKa values and protonate by taking into
> account
> > > the
> > > > effect of the ligand? I found in the manual a program named calcpka
> > but I
> > > > cannot understand the arguments it takes. Is there any other tool
> that
> > > you
> > > > would recommend for that purpose?
> > > >
> > > > thanks in advance,
> > > > Thomas
> > > >
> > > >
> > > >
> > > > --
> > > >
> > > >
> ======================================================================
> > > >
> > > > Thomas Evangelidis
> > > >
> > > > PhD student
> > > > University of Athens
> > > > Faculty of Pharmacy
> > > > Department of Pharmaceutical Chemistry
> > > > Panepistimioupoli-Zografou
> > > > 157 71 Athens
> > > > GREECE
> > > >
> > > > email: tevang.pharm.uoa.gr
> > > >
> > > > tevang3.gmail.com
> > > >
> > > >
> > > > website: https://sites.google.com/site/thomasevangelidishomepage/
> > > > _______________________________________________
> > > > AMBER mailing list
> > > > AMBER.ambermd.org
> > > > http://lists.ambermd.org/mailman/listinfo/amber
> > > >
> > >
> > >
> > >
> > > --
> > > T. Dwight McGee Jr.
> > > Quantum Theory Project
> > > University of Florida
> > > Graduate Student
> > > dwight.mcgee.gmail.com
> > >
> > > "Problems cannot be solved at the same level of awareness that created
> > > them."
> > > Albert Einstein
> > > _______________________________________________
> > > AMBER mailing list
> > > AMBER.ambermd.org
> > > http://lists.ambermd.org/mailman/listinfo/amber
> > >
> >
> >
> >
> > --
> >
> > ======================================================================
> >
> > Thomas Evangelidis
> >
> > PhD student
> > University of Athens
> > Faculty of Pharmacy
> > Department of Pharmaceutical Chemistry
> > Panepistimioupoli-Zografou
> > 157 71 Athens
> > GREECE
> >
> > email: tevang.pharm.uoa.gr
> >
> > tevang3.gmail.com
> >
> >
> > website: https://sites.google.com/site/thomasevangelidishomepage/
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
>
>
>
> --
> ================================ Current Address =======================
> Brian Radak : BioMaPS
> Institute for Quantitative Biology
> PhD candidate - York Research Group : Rutgers, The State
> University of New Jersey
> University of Minnesota - Twin Cities : Center for Integrative
> Proteomics Room 308
> Graduate Program in Chemical Physics : 174 Frelinghuysen Road,
> Department of Chemistry : Piscataway, NJ
> 08854-8066
> radak004.umn.edu :
> radakb.biomaps.rutgers.edu
> ====================================================================
> Sorry for the multiple e-mail addresses, just use the institute appropriate
> address.
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
--
======================================================================
Thomas Evangelidis
PhD student
University of Athens
Faculty of Pharmacy
Department of Pharmaceutical Chemistry
Panepistimioupoli-Zografou
157 71 Athens
GREECE
email: tevang.pharm.uoa.gr
tevang3.gmail.com
website: https://sites.google.com/site/thomasevangelidishomepage/
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Received on Thu Nov 14 2013 - 13:00:02 PST
