Dear Andrew,
May-be one day you will decide to run a big QM job to correctly define
your Zinc complex ;-) For instance in our case, we are used to run
several R.E.D. Server Development jobs that take more than 2 weeks.
After having characterized the optimized geometry, checked the
corresponding wavefunction and the 2nd derivative (used in FFParmDev),
MEPs can be computed and charges derived. Only at that time, you can
get an accurate FF so correct MD simulations (just my personal
opinion). But it looks like you finally decided to run such a QM job ;-)
Then, once your 'bonding' complex is characterized by MD simulations
you might decide to set the total charge of your Zinc atom to +2 and
remove the bonding parameters for the metal center; However, even in
this case we start from the QM optimized complex and re-fit the
charges to the entire complex (i.e. with the connecting residues but
without the atom connectivities related to the metal center in the P2N
file) applying an intra-molecular charge constraint (i.e. INTRA-MCC
keyword in R.E.D.) to the wanted integer value; at that time and after
having rebuilt the prmtop file you can remove the bonding FF
parameters and use the integer charge value for the metal atom
starting from a representative MD snapshot obtained with the bonding
parameters and a non-integer charge value for the Zinc atom.
Charge derivation for the two different approaches can be carried out
in a single R.E.D. IV job. See the projects F-88 & F-89 in R.E.DD.B.
by E. Vanquelef.
http://q4md-forcefieldtools.org/REDDB/projects/F-88/JavaApplet-5.php
versus
http://q4md-forcefieldtools.org/REDDB/projects/F-88/JavaApplet-6.php
(remove the MEP, axes & charge values for clarity; need to reconstruct
these Java applets; too small...)
& the RESP input defining all the constraints used:
http://q4md-forcefieldtools.org/REDDB/projects/F-88/input1.in
--
A last comment: from our calculations the bonding FF constants between
a metal and its ligands are usually relatively weak...
regards, Francois
> It looks like it is structural, but the protein structure starts to
> be destructued when I use zinc as an ion. so probably I should use
> it as linked to Cys, Cys, Cys and His to prevent self destruction
> and unfolding of protein which affects binding site even if amino
> acids which bind zinc and adjacent amino acids are constrained
> with something like 1000 constraints values.
>
> Sincerely yours,
> Andrew
>
> 13.01.2010, 08:47, "Ross Walker" <ross.rosswalker.co.uk>:
>> Hi Andrew,
>>
>> If you think the zinc is purely structural and not involved in the actual
>> binding site then you can just model it as a 2+ ion. Put TER cards around it
>> in the pdb. Call it something like residue name ZNS (for structural Zinc)
>> and give it atom name ZN.
>>
>> Then fire up leap and do:
>>
>> edit ZNS
>>
>> This will create a new unit called ZNS.
>>
>> Draw in a single new atom and then highlight and edit it.
>>
>> Set the charge to +2, the name and type to ZN.
>>
>> Then
>>
>> savemol2 ZNS ZNS.mol2
>>
>> Quit Leap.
>>
>> Create an frcmod file with the contents:
>>
>> Zinc 2+ Params
>> MASS
>> Zn 65.38
>>
>> BOND
>>
>> ANGL
>>
>> DIHE
>>
>> NONB
>> Zn 1.85 0.06
>>
>> Finally you can fire up leap:
>>
>> source leaprc.ff99SB
>> ZNS = loadmol2 ZNS.mol2
>> loadamberparams frcmod
>> foo = loadpdb foo.pdb
>>
>> And your zinc should be recognized.
>>
>> The only other thing you might have to do is make sure the protonation state
>> (HIS/HID/HIP, CYS/CYX etc) is correct for the residues surrounding the zinc
>> so you don't get H's added very close to the zinc.
>>
>> Good luck,
>> Ross
>>
>>> -----Original Message-----
>>> From: amber-bounces.ambermd.org [mailto:amber-bounces.ambermd.org] On
>>> Behalf Of Andrew Voronkov
>>> Sent: Wednesday, January 13, 2010 2:11 AM
>>> To: AMBER Mailing List
>>> Subject: [AMBER] How to avoid Zn parametrization?
>>>
>>> Dear Amber users,
>>> I have a protein which has Zn atom, bound directly to four amino acids
>>> (Tankyrase PARP domain, 2rf5 code in PDB bank).
>>> I need to test the results of docking of small ligands by MD run by
>>> evaluation of the stability of complexes. The binding site is far from
>>> Zn atom. For now I have no time to make parametrization for Zn atom as
>>> far as it seems to be rather advanced and time consuming. What options
>>> do I have?
>>> For example I haven't included Zinc in docking site while performing
>>> docking. Can I maybe make CAP molecular dynamics only for the binding
>>> site of the ligand.
>>> Probably parametrize zinc as ion, or just cut out Zn atom and fix all
>>> Zn-surrounding amino acids as in the X-ray structure?
>>>
>>> Best regards,
>>> Andrew
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Received on Thu Oct 27 2011 - 01:30:03 PDT
