[gmx-users] Metal-Protein interactions

[RAHUL SURESH]

Thank you Justin.

It was helpful

On Wed, Nov 29, 2017 at 7:33 AM, Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> On 11/28/17 1:00 PM, RAHUL SURESH wrote:
>
>> On Tue, 28 Nov 2017 at 7:14 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>
>>
>>> On 11/28/17 4:54 AM, RAHUL SURESH wrote:
>>>
>>>> I am trying to simulate a metal-protein interaction using gromacs 2016
>>>> package and charmm36 ff.
>>>> I have prepared the initial pdb by performing an oniom calculations
>>>>
>>> between
>>>
>>>> protein and metal (at various positions) using gaussian 09 and chose the
>>>> structure with maximum binding energy. The metal ion is bonded to oxygen
>>>> atom of His residue. Having a look at gro file after each step
>>>>
>>> That's unusual; His typically coordinate metals via their delta or
>>> epsilon N atoms.
>>>
>>> Sorry that I pronounced wrongly as oxygen.. regret the inconvenience.
>>
>> (protein.gro, em.gro, nvt.groand npt.gro) the distance between metal  ion
>>>> and the oxygen atom keeps increasing starting from 2.06 to 2.69. Over
>>>> the
>>>> course of simulations for 10ns, the metal ion is away from the protein.
>>>>
>>>> What can be done to have the metal ion restrained at its position? Or if
>>>>
>>> I
>>>
>>>> extend the simulation will the metal ion find its appropritae position
>>>> during the course time?
>>>>
>>> Unlikely. This is a fundamental issue with classical mechanical force
>>> fields approximating ion interactions very poorly, particularly in the
>>> case of multivalent and/or transition metals. There are many effects
>>> like polarization and charge transfer that simply can't be modeled. You
>>> can apply distance restraints (or actual covalent bonds), NBFIX LJ
>>> parameters, etc.
>>>
>> while restraing the metal ion, it arise an error stating that an atom can
>> not be mentioned in two groups.
>> Tc grps = protein_cu water_and_ions.
>> Cu will already be mentioned in ions.
>>
>
> It should be grouped with the protein; a coordinated metal is functionally
> part of the protein and should be treated as such. It makes no sense to
> couple it to the solvent thermostat.
>
> and that may be enough to preserve the binding pose. In
>>
>>> reality, one would have to reparametrize any ligating residues because
>>> the charge distribution on the ion and anything coordinating it is not
>>> at all what the standard force field uses.
>>>
>> Reparameterize.? Means I have to add additional parameter file to the
>> charmm36 ff after interacting with metal ion.?
>>
>
> It means you would have to derive new residue definitions, but a QM/MM
> approach is probably superior.
>
>
>> Also Justin, what if I can manually add a bond between N of HIS and metal
>> ion with most appropriate bond length ..?
>> (To avoid complexity if it works)
>>
>
> Yes, that is a possibility, but again you will have to do some QM work to
> properly parametrize the geometries and vibrational frequencies for the new
> bonded parameters (which then include angles and dihedrals). Cu2+ is a
> difficult ion to deal with, though, so this may be surprisingly laborious.
>
>
> -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.biochem.vt.edu/people/faculty/JustinLemkul.html
>
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-- 
*Regards,*
*Rahul Suresh*
*Research Scholar*
*Bharathiar University*
*Coimbatore*