[gmx-users] constant protonation state MD

[Jesper Sørensen]

Shahid,

This must be system dependent then because there are experimental methods, e.g. NMR and CD, that can help determine the secondary structure of proteins/peptides are various pH ranges.
What is your system? A peptide? A globular protein?

Best,
Jesper

On May 3, 2013, at 7:33 PM, shahid nayeem <msnayeem at gmail.com> wrote:

> 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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