Hello! There are no standard uncharged N-terminal and C-terminal residues in
Amber.
On Tue, Apr 20, 2010 at 2:23 PM, Andrew Voronkov <drugdesign.yandex.ru>wrote:
> 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
> > >>> ===================================================================
> > >>>
> > >>> _______________________________________________
> > >>> AMBER mailing list
> > >>> AMBER.ambermd.org
> > >>> http://lists.ambermd.org/mailman/listinfo/amber
> > >>
> > >>
> > >>
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> > >>
> > >>
> > >
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>
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--
Dmitry Nilov,
Lomonosov Moscow State University
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Received on Tue Apr 20 2010 - 04:00:04 PDT
