Dear Thomas,
> I think I mentioned in my first email that the tyr is coordinating a
> heme group. For the heme we plan to use standard parameters. Therefore,
> the non integer charge of the Fe should be already considered in the
> heme parameters. One big problem is that in the process we are looking
> at, the coordination between heme and tyr will be broken. This will
> probably also cause the tyr to get protonated. Nevertheless, I would
> like to run the MD with the deprotonated tyr, since we first start with
> the coordination intact. Probably some more sophisticated simulation
> techniques (constant pH or QM/MM) are needed to describe the full
> process. But I need to get an idea about the process with a classical MD
> first. My hope is that we can separate the unbinding of the heme and the
> protonation of the tyr.
by QM/MM you mean semi-emp./MM: right?
> If nobody else has parameters for tyr(-), I will try to build the
> parameters with RED without including the metal ion. I hope that this
> will give the best approximation for both the coordinated as well as the
> free tyr(-) (even if this probably does not exists very long).
Yes, sorry, I missed the information related to 'heme' in your former email...
Several points:
- Concerning heme, see the work of Shahrokh et al. JCC 2012:
http://onlinelibrary.wiley.com/doi/10.1002/jcc.21922/abstract
- If Tyr(-) is connected to the Fe atom of heme, I would NOT consider
Tyr(-) isolated from the heme...
- You need to think to what is (i) the basis set + theory level to be
used in geometry optimization & MEP computation in your case (ii) look
at RESP vs ESP charges for your complex (iii) define the radius for Fe
to be used in MEP computation, and (iv) think to the atoms of the
Fe-complex to be involved in QM, and check the corresponding QM
optimized geometry obtained.
Concerning:
(i) -> you might download R;E.D. & modify its source code to
incorporate a new QM method for geometry optimization & MEP
computation, or you might use R.E.D. Server "Development" instead of
R.E.D. Server.
See
http://q4md-forcefieldtools.org/REDS-Development/popup/popkeyword.php
vs
http://q4md-forcefieldtools.org/REDS/popup/popkeyword.php
(ii) -> compare both sets of charges; for instance; see in R.E.DD.B.
http://q4md-forcefieldtools.org/REDDB/projects/F-88/
vs
http://q4md-forcefieldtools.org/REDDB/projects/F-89/
(iii) use R.E.D. Server "Development" to be able to modify the Fe radius
http://q4md-forcefieldtools.org/REDS-Development/popup/popradius.php
(iv) I will forward in the Amber mailing list an email we sent to the
q4md-fft mailing about constraints used during geometry optimization;
this should help you to get a QM optimized geometry in agreement with
experimental data...
regards, Francois
> FyD schrieb:
>> Dear Florent, Albert and Thomas,
>>
>> Yes and if this Tyr(-) residue is connected to a metal ion, the charge
>> derivation approach is different: the entire site (metal + all
>> ligands/residues) has to be considered and involved in the QM job. In
>> this case, the partial charge of the metal ion in the complex is far
>> lower than the expected integer value...
>>
>> in this case, R.E.D. Server or R.E.D. Server Development can be used...
>> http://q4md-forcefieldtools.org/REDS/
>> http://q4md-forcefieldtools.org/REDS-Development/
>>
>> regards, Francois
>>
>>
>>> Tyrosine can be deprotonated in the vicinity of a metallic cation.
>>> Moreover, in electronic transfer of photosynthetic reactions a
>>> specific tyrosine is deprotonated. See
>>> http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0026808
>>> for an example of such system.
>>
>>
>>> On Sun, 05 Feb 2012 09:16:17 +0100
>>> Albert<mailmd2011.gmail.com> wrote:
>>>> I am just curious about in which condition the Tyr would be
>>>> deprotanated? As far I know , from the aspect of pKa, it is very
>>>> difficult for Tyr to be deprotanted.....
>>>>
>>>>
>>>> On 02/05/2012 09:04 AM, FyD wrote:
>>>>> Dear Thomas,
>>>>>
>>>>>> I would like to simulate a heme binding protein. In this protein,
>>>>>> the
>>>>>> heme is coordinated by a his and a tyr. From experimental
>>>>>> investigations
>>>>>> it is clear that the tyr is deprotonated. But unfortunately, I
>>>>>> cannot
>>>>>> find any parameters for the deprotonated tyr. Has anybody out there
>>>>>> such
>>>>>> parameters and is willing to share them.
>>>>> You need a molecular fragment for this Tyr(-); three fragments can
>>>>> be
>>>>> built: N-terminal, C-terminal and central. This is likely you only
>>>>> need the central one; See:
>>>>> http://q4md-forcefieldtools.org/Tutorial/Tutorial-1.php#10 using
>>>>> R.E.D.
>>>>> http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#15 using
>>>>> R.E.D.Server
>>>>>
>>>>> Now R.E.D. Server can generate the three fragments in a single step;
>>>>> See:
>>>>> http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#24
>>>>> vs
>>>>> http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#25
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Sun Feb 05 2012 - 11:30:02 PST
