[gmx-users] simulation in acidic condition

Sat Oct 13 08:17:37 CEST 2018

Den 2018-10-13 kl. 01:18, skrev Alex:
> I am not aware of any forcefield with an established H3O+ ion model (and it
> is a pretty complicated subject), so you would need to develop the
> hydronium ion model yourself and justify its use instead of things like
> KCl/NaCl.

There are quite a few H3O+ models, both simple point charge and 
polarizable. But it is somehow besides the point. What the original 
poster sets out to do is to study denaturation due to acids. As Justin 
correctly pointed out the only way to mimic that is to *change the 
protonation state of the protein* (not: to protonate the protein). That 
means at a lower pH more Asp and Glu sidechains will be protonated.

This gives you a combinatorial problem (which of the Asp and Glu) that 
is coupled to the structure: where the protons are added influences the 
structure and vice versa. So you are look at doing dozens or hundreds of 
long simulations to study this.

There *is* an implementation of constant pH simulations in gromacs, but 
it is slow last time we played with it. Check work by Donninni and Groenhof.

> 
> Alex
> 
> On Fri, Oct 12, 2018 at 4:27 PM ali khamoushi <khamuoshia at gmail.com> wrote:
> 
>> Thanks for your answers. so, I leave you with one more question. if I use
>> HCL ions in shape of H3O+ and Cl- instead of NaCl for neutralization, isn't
>> it disrupt system?
>>
>> On Sat, Oct 13, 2018 at 1:46 AM Alex <nedomacho at gmail.com> wrote:
>>
>>> Noone knows if "it is gonna probably work." Justin simply suggested the
>>> only way to modify pH in this type of simulations. You can certainly use
>> an
>>> excess of appropriate ion types added to the solvent to neutralize the
>>> system overall. Whether it gives you any answers we don't know.
>>>
>>> Alex
>>>
>>> On Fri, Oct 12, 2018 at 4:07 PM ali khamoushi <khamuoshia at gmail.com>
>>> wrote:
>>>
>>>> I deeply understood your explanation. so, if first I protonate protein,
>>>> then neutralize charge of protein with ions like NaCl and run MD
>>>> simulation, is it gonna probably work and give me answer? I just wanna
>>> know
>>>> that is my protein going to denature in this condition (which I prefer
>>> call
>>>> it so-called acidic PH condition) or not?
>>>>
>>>> On Sat, Oct 13, 2018 at 1:18 AM Justin Lemkul <jalemkul at vt.edu> wrote:
>>>>
>>>>>
>>>>>
>>>>> On 10/12/18 5:43 PM, ali khamoushi wrote:
>>>>>> so, if I protonate my protein and then put it in neutral condition,
>>> is
>>>> it
>>>>>> going to work? I mean should I use particular ions for
>>> neutralization?
>>>>>
>>>>> Plainly, there is no such thing as "pH" in an MD simulation. pH
>> refers
>>>>> to the -log[H+], of which there are none in the MD simulation. So
>>> you're
>>>>> not putting anything into a "neutral condition." The protonation
>> state
>>>>> is what you set it to be. If that reflects the dominant protonation
>>>>> state at some real-world pH value, then that's all it is. The rest of
>>>>> the solution doesn't have a pH.
>>>>>
>>>>> Neutralization with ions is a separate issue. But neutralization of
>>>>> charge is not the same as "neutral pH."
>>>>>
>>>>> -Justin
>>>>>
>>>>>> On Sat, Oct 13, 2018 at 12:56 AM Justin Lemkul <jalemkul at vt.edu>
>>>> wrote:
>>>>>>
>>>>>>>
>>>>>>> On 10/12/18 5:14 PM, ali khamoushi wrote:
>>>>>>>> hello everyone. I want to simulate a protein without ligand in
>>>> gromacs
>>>>> in
>>>>>>>> acidic conditions. but I don't know what exactly I must do.
>> should
>>> I
>>>>> add
>>>>>>>> HCL ions (for example) to turn neutral surrounding into acidic?
>>>>>>>> my protein is Insulin. and I want to see behavior of his protein
>> in
>>>>>>> acidic
>>>>>>>> condition.
>>>>>>> If you really want to monitor pH sensitivity, you should be doing
>> a
>>>>>>> constant-pH simulation. For that, you need to look for other
>>> software,
>>>>>>> because you can't do those kinds of simulations in GROMACS.
>>>>>>>
>>>>>>> Adding explicit HCl (which really should be H3O+ and Cl-) isn't
>>>>>>> appropriate either, because as soon as you have one hydronium ion
>>> in a
>>>>>>> simulation box, the pH is actually astronomically low (do the math
>>> and
>>>>>>> you'll see), and as well it's neither physically realistic nor
>>> useful.
>>>>>>>
>>>>>>> The cheap approach that people often use is to simply protonate
>> the
>>>>>>> biomolecule according to the dominant state at a given pH and
>>> simulate
>>>>>>> it that way. It's an approximation, but it may work.
>>>>>>>
>>>>>>> -Justin
>>>>>>>
>>>>>>> --
>>>>>>> ==================================================
>>>>>>>
>>>>>>> Justin A. Lemkul, Ph.D.
>>>>>>> Assistant Professor
>>>>>>> Virginia Tech Department of Biochemistry
>>>>>>>
>>>>>>> 303 Engel Hall
>>>>>>> 340 West Campus Dr.
>>>>>>> Blacksburg, VA 24061
>>>>>>>
>>>>>>> jalemkul at vt.edu | (540) 231-3129
>>>>>>> http://www.thelemkullab.com
>>>>>>>
>>>>>>> ==================================================
>>>>>>>
>>>>>>> --
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>>>>>
>>>>> --
>>>>> ==================================================
>>>>>
>>>>> Justin A. Lemkul, Ph.D.
>>>>> Assistant Professor
>>>>> Virginia Tech Department of Biochemistry
>>>>>
>>>>> 303 Engel Hall
>>>>> 340 West Campus Dr.
>>>>> Blacksburg, VA 24061
>>>>>
>>>>> jalemkul at vt.edu | (540) 231-3129
>>>>> http://www.thelemkullab.com
>>>>>
>>>>> ==================================================
>>>>>
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