oh, I see !
than yes, Jason's advice is what you need to do.
a,
On 3/3/17 10:01 AM, Eric Lang wrote:
> 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
>>
>>
>> _______________________________________________
>> AMBER mailing list
>> AMBER.ambermd.org
>> http://lists.ambermd.org/mailman/listinfo/amber
>>
>
>
--
Dr. Adrian E. Roitberg
University of Florida Research Foundation Professor.
Department of Chemistry
University of Florida
roitberg.ufl.edu
352-392-6972
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Fri Mar 03 2017 - 07:30:03 PST
