[gmx-users] constant protonation state MD

[shahid nayeem]

Thanks a lot Erik and Baptista
I am interested in simulating the change in secondary structure which is
supposed to be influenced by the change in the pH environment of the cell.
Experimentally it is not known but it has been proposed by many that the
change in pH leads to change in conformation. I did constant protonation
state MD at two different pH. I got an alpha helix converting to beta sheet
at higher pH but not at lower pH. I am bothered to prove the reliability of
the simulation results as experimentally it cant be established.

Shahid


On Sat, May 4, 2013 at 5:46 AM, <baptista at itqb.unl.pt> wrote:

> 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<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<http://www.itqb.unl.pt/~baptista>
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