[gmx-users] Metal-Protein interactions

[RAHUL SURESH]

Dear Justin

I have manually added Cu ion to the protein structure. the total charge of
the system is -0.99999. How do I make sure that  gromacs is considering Cu
in +2 state only?

thank you

On Wed, Nov 29, 2017 at 4:33 PM, RAHUL SURESH <drrahulsuresh at gmail.com>
wrote:

> 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*
>



-- 
*Regards,*
*Rahul Suresh*
*Research Scholar*
*Bharathiar University*
*Coimbatore*