Only because I've "think" I've seen H++ mess up when I gave it a protonated
structure, after a bunch of manipulations to a pdb file, I somehow ended up
with 2 sets of hydrogens added to each residue... call it superstition :-)
Dean
"All new truths begin as heresy."
Fox Mulder
Dr. Dean Cuebas, Associate Prof of Chemistry
deancuebas.missouristate.edu, Ph 417-836-8567 FAX 417-836-5507
Dept. of Chemistry, Missouri State University
Springfield, Missouri 65897
> From: Andrew Voronkov <drugdesign.yandex.ru>
> Reply-To: AMBER Mailing List <amber.ambermd.org>
> Date: Tue, 20 Apr 2010 08:24:15 -0500
> To: AMBER Mailing List <amber.ambermd.org>
> Subject: Re: Re: [AMBER] how is pH treated in Amber - other than constant pH
> simulations
>
> Btw, why do you suggest to use not protonated structure from MolProbity first?
> Well at least for my pretty simple protein the H++ predictions, based on
> protonated and non-protonated models from MolProbity look pretty the same, so
> why not to use protonated one?
>
> Best regards,
> Andrew
>
>
> 16.04.10, 11:53, "Dean Cuebas" <deancuebas.missouristate.edu>:
>
>>
>> Dear Andrew,
>>
>> I have found the best approach to protonating my proteins is to use the pKa
>> predictions of the H++ server in conjunction with the superior H-bonding
>> prediction of reduce at the Molprobity server.
>>
>> 1) Use Molprobity to flip Asn, Gln, His residues as needed, since MOST
>> proteins from XRC need fixing in this regard.
>> 2) Save the flipped but NOT protonated pdb to use as input to the H++ server
>> for pKa predictions.
>> 3) Continue with the Molprobity server to maximize H-bonding possibilities
>> and protonate the protein.
>>
>> 4) Using visual inspection of the molprobity output for h-bond and clashes,
>> and the pKa predictions of H++ you can come to some reasonably confident
>> expectations, especially with regards to the correct state of histidine,
>> picking the correct HID or HIE neutral annular tautomer, or the protonated
>> HIP.
>>
>> Realize that constant pH cannot be used with explicit water MD, so if you
>> use a water box, you should do the above.
>>
>> Hope this helps!
>>
>> Dean
>>
>>
>>> From: Carlos Simmerling
>>> Reply-To: AMBER Mailing List
>>> Date: Fri, 16 Apr 2010 11:10:42 -0500
>>> To: AMBER Mailing List
>>> Subject: Re: [AMBER] how is pH treated in Amber - other than constant pH
>>> simulations
>>>
>>> simulations in amber are either constant pH or constant protonation.
>>> default protonations are reasonable for the isolated amino acids, but
>>> pka shifts may occur in proteins. it is possible to calculate pkas for
>>> the initial structure, assign protonation states, and keep them. this
>>> is ok as long as there are not conformation dependent pka changes that
>>> cross your pH.
>>>
>>> On 4/16/10, Andrew Voronkov wrote:
>>>> Dear Amber users,
>>>> when I am looking for questions about pH and Amber I get mostly information
>>>> about constant pH simulations. But what pH is supposed to be by default,
>>>> without constant pH simulations? Just neutral or what it depends from?
>>>> As I understand in Amber pH is mostly set by protonation state of the
>>>> molecules, so if not going to constant pH simulation I can approximately
>>>> imitate some pH by setting corresponding protonation state distribution of
>>>> amino acids. If physiological pH is required for protein simulation what
>>>> can
>>>> be general recommendation here - instant pH or default pH treatment?
>>>>
>>>> Sincerely yours,
>>>> Andrew
>>>>
>>>> _______________________________________________
>>>> AMBER mailing list
>>>> AMBER.ambermd.org
>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>
>>>
>>>
>>> --
>>> ===================================================================
>>> Carlos L. Simmerling, Ph.D.
>>> Professor, Department of Chemistry
>>> CMM Bldg, Room G80 Phone: (631) 632-1336 Fax: 632-1555
>>> Stony Brook University E-mail: carlos.simmerling.gmail.com
>>> Stony Brook, NY 11794-5115 Web: http://www.simmerlinglab.org
>>> ===================================================================
>>>
>>> _______________________________________________
>>> AMBER mailing list
>>> AMBER.ambermd.org
>>> http://lists.ambermd.org/mailman/listinfo/amber
>>
>>
>>
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Received on Tue Apr 20 2010 - 08:30:02 PDT
