Hi Adrian,
Sorry my question was perhaps unclear as I referred heavily on the previous
email exchanges.
I am interested in the reference Histidine compound, I am not talking about
a particular protein at this stage.
I just want to fine tune the reference energy based on the relatively long
pH-REMD performed on the reference compound using ff14SB, so I indeed have
a reference His that titrate at 6.5 and 7.1.
So I will follow Jason's approach and turn off one state first and then the
other
Thanks,
Eric
On 3 March 2017 at 14:51, Adrian Roitberg <roitberg.ufl.edu> wrote:
> Hi
>
> It is not clear to me what you want to do.
>
> Why would the two histidines have a different reference free energy? If
> the reference compound is the free histidine in solution, then it has
> just the two regular pkas. CphMD would then compute the delta pka from
> that value, when they are inside the protein.
>
> The fact that the two histidines have different pkas inside the protein
> should be a result of the cphmd calculation, not the input to it.
>
>
> adrian
>
>
> On 3/3/17 9:47 AM, Jason Swails wrote:
> > On Fri, Mar 3, 2017 at 9:33 AM, Eric Lang <eric.lang.bristol.ac.uk>
> wrote:
> >
> >> Hello,
> >>
> >> I was wondering, if I want to correct the reference energy for Histidine
> >> residue can I use the same formula TI = Ref Energy + R*T*ln(10)*pKa ? In
> >> that case how do I deal with the two sites that have a different pKa?
> >> Can I just run the pH-REMD (at pH = pKa ± 0.1 pKa ± 0.2 pKa ± 1.2)
> using
> >> pKa=6.5 and then do the same for pKa=7.1 and then correct TI for each
> pKa?
> >> It sounds too simple to do that in the case of His and I fell like
> there is
> >> more hidden complexity because of the two sites?
> >>
> > ​What I did was hack the cpinutil.py script to turn turn off one state
> (so
> > the generated cpin file only contained one protonation state). Treat
> this
> > the same way you would any non-tautomeric state.​
> >
> > Do the same thing for the other site, and you have your two reference
> > energies.
> >
> > HTH,
> > Jason
> >
>
> --
> Dr. Adrian E. Roitberg
> University of Florida Research Foundation Professor.
> Department of Chemistry
> University of Florida
> roitberg.ufl.edu
> 352-392-6972
>
>
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>
--
Eric Lang
BrisSynBio Postdoctoral Research Associate Modelling
Centre for Computational Chemistry
School of Chemistry - University of Bristol
Bristol BS8 1TS - United Kingdom
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Received on Fri Mar 03 2017 - 07:30:02 PST
