A bit more general question. For example I've got pKa which correspond to protonated state of amido group of N-terminal amino acid or deprotonated state of C-term carboxylic group. How is possible in amber to discriminate by names between protonated\deprotonated C- and N- terminal amido and carboxylic groups?
Best regards,
Andrew
16.04.10, 15:05, "Dean Cuebas" :
>
> > From: Andrew Voronkov
> > Reply-To: AMBER Mailing List
> > Date: Fri, 16 Apr 2010 13:17:32 -0500
> > To: AMBER Mailing List
> > Subject: Re: Re: [AMBER] how is pH treated in Amber - other than constant pH
> > simulations
> >
> > Thank you that is actually what I do. The prediction by H++ server with
> > isntant protonation, just wondered if this fits to Amber pH strategy without
> > constant pH. As to H-bonds from Molprbity - aren't H bonds supposed to result
> > mostly from MD simulations?
>
> I might have been a bit confusing here...
> What I meant was that the way that molprobity (the reduce app) adds
> hydrogens to especially histidine tends to be better than H++ in that it
> assigns delta versus epsilon tautomers. In fact, I've only seen H++
> assigning uncharged histidines as epsilon, whereas reduce will assign delta
> and visually it is very clear that a strong H-bond from another residue to
> the delta H of a particular HIS is clearly preferred over an epsilon without
> such h-bond stabilization. On the other hand, H++ pka predictions usually
> help with deciding to have protons on both delta and epsilon nitrogens.
>
> Of course you can go the whole mile and do an iterative process where you
> now do MD on your first set of protonation predictions and then resubmit to
> molprobity and H++ to see if you converge on a stable set of predictions.
>
> Dean
> > Btw as I can see many parameters like Z-score significantly improve after MD
> > even against X ray structures.
> >
> > Best regards,
> > Andrew
> >
> > 16.04.10, 11:53, "Dean Cuebas" :
> >
> >>
> >> 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
> >>> ===================================================================
> >>>
> >>> _______________________________________________
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> >>> AMBER.ambermd.org
> >>> http://lists.ambermd.org/mailman/listinfo/amber
> >>
> >>
> >>
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> >
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>
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Received on Tue Apr 20 2010 - 03:30:04 PDT
