at normal pH one does not expect to see protonated C terminus or
deprotonated N terminus. Normally if you want a neutral terminal, a blocking
group is added in the experiment (acetylating or amidating the end). so how
you proceed depends on what experimental conditions you are trying to
reproduce. If you really think you have an unusual protonation state for a
terminal group, you need to develop your own residue. You might check recent
literature on constant pH simulations (such as from the Roitberg lab) to see
if they included termini as well as the ionizable side chains.
On Tue, Apr 20, 2010 at 7:27 AM, Andrew Voronkov <drugdesign.yandex.ru>wrote:
> Yes, I have found none in manual and I wonder what is generally done in
> this case and if this was somehow considered.
>
> 20.04.10, 14:43, "Dmitry Nilov" <nilovdm.gmail.com>:
>
> > 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 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
> > > > >>
> > > > >>
> > > > >>
> > > > >> _______________________________________________
> > > > >> AMBER mailing list
> > > > >> AMBER.ambermd.org
> > > > >> http://lists.ambermd.org/mailman/listinfo/amber
> > > > >>
> > > > >>
> > > > >
> > > > > _______________________________________________
> > > > > AMBER mailing list
> > > > > AMBER.ambermd.org
> > > > > http://lists.ambermd.org/mailman/listinfo/amber
> > > >
> > > >
> > > >
> > > > _______________________________________________
> > > > AMBER mailing list
> > > > AMBER.ambermd.org
> > > > http://lists.ambermd.org/mailman/listinfo/amber
> > > >
> > > >
> > >
> > > _______________________________________________
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> > > AMBER.ambermd.org
> > > http://lists.ambermd.org/mailman/listinfo/amber
> > >
> >
> >
> >
> > --
> > Dmitry Nilov,
> > Lomonosov Moscow State University
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
> >
>
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Received on Tue Apr 20 2010 - 05:00:03 PDT
