[gmx-users] -inter command

[Justin Lemkul]

On 1/19/18 7:25 AM, zaved at tezu.ernet.in wrote:
>> Message: 3
>> Date: Thu, 18 Jan 2018 07:39:39 -0500
>> From: Justin Lemkul <jalemkul at vt.edu>
>> To: gmx-users at gromacs.org
>> Subject: Re: [gmx-users] -inter command
>> Message-ID: <0281054c-c062-90c3-2243-ef0f5f3ed6c2 at vt.edu>
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>> On 1/18/18 7:02 AM, zaved at tezu.ernet.in wrote:
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>>>>      1. Re: -inter command (Jo?o Henriques)
>>>>      2. Rupture force definition (Rakesh Mishra)
>>>>      3. Re: Can I get the fraction of solvent accessible	surface area
>>>>         using "gmx sasa"? (=?ISO-8859-1?B?WkhBTkcgQ2hlbmc=?=)
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>>>> Message: 1
>>>> Date: Tue, 16 Jan 2018 08:30:10 +0100
>>>> From: Jo?o Henriques <joao.m.a.henriques at gmail.com>
>>>> To: gmx-users at gromacs.org
>>>> Subject: Re: [gmx-users] -inter command
>>>> Message-ID:
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>>> Thank you so much Joao Sir for your kind response.
>>>
>>> 1. I have predicted the pka values for my protein using H++ server.
>>>
>>> 2. Based on the pka values, I have set the protonation states of the
>>> charged residues using -inter command for pH 9.
>>>
>>> 3.I have run my simulation at pH 9 (keeping charge of +8e) using gromacs
>>> 5.1.4 and gromos54a7 ff.
>>>
>>> After performing 100ns simulation, I didn't observed any change compared
>>> to control system.
>>>
>>> Can you provide any advice on it?
>> In what ways do the "pH 9" and "control" simulations differ? What do you
>> define as "control" in this instance, default protonation by pdb2gmx? If
>> that's the case, unless you have some very noncanonical pKa values,
>> there's nothing that's really expected to be different between these two
>> pH values, except perhaps the N-terminus itself.
>>
>> What are you trying to compare or calculate? Perhaps 100 ns is
>> insufficient to observe whatever it is you're after. How have you
>> quantified that there is no difference/change between these systems?
>>
>> -Justin
>
> Thank you so much Justin.
>
> 1. Yes you are correct. control here means default protonation state and
> in this case the system charge of +8e is neutralized. I didn't have any
> noncanonical pka values (at ph9). Checked with both H++ server and Propka.
> For ph 9, I have kept the charge of +8e.
>
> 2. Our experimental data suggests that at higher pH (9), the protein
> initiates unfolding.
>
> 3. I have taken the final structure (at 100ns) of both systems and
> superimposed it. I got a RMSD of 1.030 angstrom and no major structural
> change was observed.
>
> 4. We can consider to extend the simulation to visualize any change, if
> above things are correct.

There won't be one. Since the topologies are identical, you're running 
the same simulation twice, and concluding that there are no major 
variations between the two. You don't actually have any simulation that 
you can claim is representing anything other than "pH 7," though pH 
isn't really a thing in fixed-charge/fixed-topology MD. This is a 
limitation of modeling something with fixed protonation states; it 
doesn't necessarily reflect reality. A constant pH method might show 
some results, but AFAIK this is not possible in GROMACS (though some 
people do have custom code in old versions that might work). You may 
want to consider a different program like AMBER or CHARMM that can do 
these types of simulations.

-Justin

-- 
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Justin A. Lemkul, Ph.D.
Assistant Professor
Virginia Tech Department of Biochemistry

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