[gmx-users] constant protonation state MD

[baptista at itqb.unl.pt]

Hi Shahid,

As Erik said, it depends... on your system, on the process you are 
studying in that system, on the property you think it's relevant to study 
that process, etc.

If your question refers to the (de)protonation of acidic and basic groups 
usually occuring in aqueous solution, there are methods to perform what is 
called constant-pH MD, where the protonation states of those groups change 
in a discrete or continuous way along the simulation. If you are 
interested, start with the corresponding GROMACS how-to 
(http://www.gromacs.org/Documentation/How-tos/Constant_pH_Simulation) and 
then search the literature.

In any case, you don't need any of that fancy stuff unless you have 
reasons to think that the properties you want to study in your system are 
strongly dependent on protonation-conformation coupling effects. In some 
cases you may be suspicious about the effect of the protonation state of 
one group (e.g., a histidine), but that can be simply tested by performing 
two constant-protonation MD simulations, one for each state (you can even 
try to use a linear response approximation on top of that). But in most 
cases you don't need even that.

For what it's worth: I was one of the first to develop and apply 
constant-pH MD and I don't bother to use it most of the time... :)

Best,
Antonio

On Fri, 3 May 2013, Erik Marklund wrote:

> Yes that's what lambda dynamics does. I mentioned it since it addresses the interplay between protonation and structure. So to answer your original question: it depends.
>
> Erik
>
> On 3 May 2013, at 15:27, shahid nayeem <msnayeem at gmail.com> wrote:
>
>> If I know correctly in lambda dynamics the dynamics of
>> protonation/deprotonation equilibria is accounted for while my question
>> relates to the typical constant protonation MD where each titratable group
>> remains in one protonation state throughout the simulation. Please educate
>> me
>> Shahid
>>
>>
>> On Fri, May 3, 2013 at 6:22 PM, Erik Marklund <erikm at xray.bmc.uu.se> wrote:
>>
>>> I don't have one in mind. It's a delicate question and perhaps I shouldn't
>>> have phrased it the way I did. Nevertheless, the pKa of most side chains
>>> mean that their protonation will be dominated by one state for most pH
>>> values. pKa-shifts and complicated interplay between protonation and
>>> structure cause exceptions to this and you should be aware that such things
>>> may in some cases be important. Also consider the timescales of pH-depedent
>>> structural changes and the length of your simulations. You could check out
>>> the papers on lambda dynamics by C. Brooks III for an interesting take on
>>> sampling multiple protonation states.
>>>
>>> Best,
>>>
>>> Erik
>>>
>>> On 3 May 2013, at 14:05, shahid nayeem <msnayeem at gmail.com> wrote:
>>>
>>>> Thanks a lot Erik. Could I get some reference based on which you say that
>>>> much of the structural biology will be largely unaffected.
>>>>
>>>> Shahid
>>>>
>>>>
>>>> On Fri, May 3, 2013 at 1:05 PM, Erik Marklund <erikm at xray.bmc.uu.se>
>>> wrote:
>>>>
>>>>> There's no general answer to that. Proton conductivity measurements, for
>>>>> instance, will be horribly wrong without dynamic protonation. Much (but
>>> not
>>>>> all) structural biology, however, will be largely unaffected.
>>>>>
>>>>> Erik
>>>>>
>>>>> On 3 May 2013, at 04:30, shahid nayeem <msnayeem at gmail.com> wrote:
>>>>>
>>>>>> Dear all
>>>>>>
>>>>>> Can someone enlighten me on the reliability of the results obtained
>>> from
>>>>>> constant protonation state (assigned by different pKa value at
>>> different
>>>>>> pH) MD simulation. Also want to know its reliability in case of
>>> implicit
>>>>>> solvation model such as PB/GB calculation.
>>>>>>
>>>>>> Shahid
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--
Antonio M. Baptista
Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa
Av. da Republica - EAN, 2780-157 Oeiras, Portugal
phone: +351-214469619         email: baptista at itqb.unl.pt
fax:   +351-214411277         WWW:   http://www.itqb.unl.pt/~baptista
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