Dear Ross, more than 1,5 years I am back to this task :)
because it became actual again.
I did molecular dynamics with zinc as ion and with weak restrains on the loop which binds zinc.
"Keep protein fixed with weak restraints
10.0"
Zinc is coordinated by two cysteines and one histidine. After 50 picoseconds zinc atom starts to migrate into the solution from cysteins and His, while other structure is not yet much affected.
It is not in the binding site, so for now as the next step I consider to fix it with more strict restrains, what restrain values can you recommend?
If that will not work then I ll need to do some QM.
Best regards,
Andrew
13.01.2010, 07:47, "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
> ššZn š1.85 šš0.06
>
> 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
>
>> š-----Original Message-----
>> šFrom: amber-bounces.ambermd.org [mailto:amber-bounces.ambermd.org] On
>> šBehalf Of Andrew Voronkov
>> šSent: Wednesday, January 13, 2010 2:11 AM
>> šTo: AMBER Mailing List
>> šSubject: [AMBER] How to avoid Zn parametrization?
>>
>> šDear Amber users,
>> šI have a protein which has Zn atom, bound directly to four amino acids
>> š(Tankyrase PARP domain, 2rf5 code in PDB bank).
>> šI need to test the results of docking of small šligands by MD run by
>> ševaluation of the stability of complexes. The binding site is far from
>> šZn atom. For now I have no time to make parametrization for Zn atom as
>> šfar as it seems to be rather advanced and time consuming. What options
>> šdo I have?
>> šFor example I haven't included Zinc in docking site while performing
>> šdocking. Can I maybe make CAP molecular dynamics only for the binding
>> šsite of the ligand.
>> šProbably parametrize zinc as ion, or just cut out Zn atom and fix all
>> šZn-surrounding amino acids as in the X-ray structure?
>>
>> šBest regards,
>> šAndrew
>>
>> š_______________________________________________
>> šAMBER mailing list
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>
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Received on Wed Sep 14 2011 - 03:30:02 PDT
