[gmx-users] Protein at given pH

[Erik Marklund]

7 nov 2012 kl. 16.21 skrev Steven Neumann:

> On Wed, Nov 7, 2012 at 2:55 PM, Erik Marklund <erikm at xray.bmc.uu.se> wrote:
>> Hi,
>> 
>> I've used the H++ server myself at times. My experience is that it's rather sensitive to the very fine detail of the input structure in some cases. I've had situations where H++ suggest one protonation state, then a short md simulation takes the system to a slightly different conformation that seem more prevalent but that yields another protonation state if sent to H++ again. Use all biochemical knowledge that you can muster to check that the output makes sense. Focus on residues that you suspect might be important for the overall question you address.
>> 
>> That said, pKa calculations are inherently difficult and can probably not be done reliably without lots of simulations. As such H++ probably come close to what we can currently accomplish within reasonable time for (nearly) static structures.
>> 
>> Best,
>> 
>> Erik
> 
> Thanks for this! Is it not better just to use pK values from the
> literature corresponding to given residue side chain? My protein is an
> alpha-helix.
> 
> Thanks,
> 
> Steven
> 

If such (reliable) data is available, then yes. Or it may serve as validation.

Erik

> 
>> 
>> 7 nov 2012 kl. 10.19 skrev Steven Neumann:
>> 
>>> Dear Gmx Users,
>>> 
>>> I am trying to simulate protein-ligand interactions at specific pH=5.
>>> I processed my protein.pdb into the H++. As I see from th titration
>>> curve of the entire molecule it appears that at pH=5 the total charge
>>> should be equal to 2. When I process the obtained pdb from the server
>>> to pdb2gmx using -ignh I get the total charge of -3. Can anyone
>>> explain me this?
>>> 
>>> In terms of small molecules how can I get parameters at specific pH? I
>>> am using Charmm and parachem.org does not support pH changes. Can
>>> anyone advise?
>>> 
>>> thank you,
>>> 
>>> Steven
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>> 
>> -----------------------------------------------
>> Erik Marklund, PhD
>> Dept. of Cell and Molecular Biology, Uppsala University.
>> Husargatan 3, Box 596,    75124 Uppsala, Sweden
>> phone:    +46 18 471 6688        fax: +46 18 511 755
>> erikm at xray.bmc.uu.se
>> http://www2.icm.uu.se/molbio/elflab/index.html
>> 
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-----------------------------------------------
Erik Marklund, PhD
Dept. of Cell and Molecular Biology, Uppsala University.
Husargatan 3, Box 596,    75124 Uppsala, Sweden
phone:    +46 18 471 6688        fax: +46 18 511 755
erikm at xray.bmc.uu.se
http://www2.icm.uu.se/molbio/elflab/index.html