On Wed, Mar 31, 2010 at 12:10:21PM +0400, Dmitri Nilov wrote:
> Many Thanks!
> Now I'm working on accurate optimization of starting geometry, but it seems
> that the main origin of error is a choice of QM region. I try to include in
> QM part both ligand and fragment of N-terminal serine (that is a key residue
> in catalysis). So I cut serine in following manner:
> H
> |
> HO-CH2-CA- linkatom - CO-protein
> |
> NH2
>
> Both OH- and neutral NH2- groups are crucial in catalysis. I know that it is
> a bad choice to cut peptide bond, but cutting CA-C bond seems to be
> dangerous too.
> Is there any way to resolve the problem? And another question for the
> future: is it reasonable to include in QM part residues, that act in
> catalysis via backbone (because I have no idea how to cut QM part from the
> rest of the protein in this case)?
>
I have a very similar situation, but with an N-term thr instead of ser. The unprotonated amine is involved in imine formation. After several trials of other possibilities, I cut the C-CA bond as the "least bad" compromise. I kept the thr side chain in the QM region to avoid having to introduce another cut, even though there is no reason to suppose the thr side chain is involved in catalysis (in my case). Sometimes compromises must be made, even though I am unhappy with this one.
Good luck,
Bud Dodson
> On Wed, Mar 31, 2010 at 1:10 AM, Ross Walker <ross.rosswalker.co.uk> wrote:
>
> > Hi Dmitry,
> >
> > > QMMM: WARNING!
> > > QMMM: Unable to achieve self consistency to the tolerances specified
> > > QMMM: No convergence in SCF after 1000 steps.
> > > QMMM: Job will continue with unconverged SCF. Warning energies
> > > QMMM: and forces for this step will not be accurate.
> > > QMMM: E = -0.8502E+06 DeltaE = 0.1024E-07 DeltaP = 0.2569E-08
> > > QMMM: Smallest DeltaE = 0.1013E-07 DeltaP = 0.2645E-08 Step =
> >
> > > Protein-ligand complex is based on crystallographic structure, thus, i
> > > believe that starting conformation is good.
> >
> > If only that were true. Often crystal structures are very poor resolution,
> > have errors and or guesses in certain parts of the structures and lack
> > protons. Net result is that even a 'good' crystal structure can represent a
> > bad starting geometry. I would start by followings Bud's advice. Minimize
> > and run some MD first classically to let the system relax. Then try turning
> > on the QM and see if the problem persists.
> >
> > > I've tried cut off 8, 9, 10; AM1 and PM3; SHAKE and NOSHAKE
> > > minimization. Example of input file is attached.
> >
> > It is also possible that your QM region is a poor choice, perhaps there are
> > link atoms across inappropriate bonds, cutting a peptide backbone for
> > example. You may also have the charge for your ligand set incorrectly
> > forcing it into some high energy state.
> >
> > Note, though that SCF got close to convergence:
> >
> > > QMMM: Smallest DeltaE = 0.1013E-07 DeltaP = 0.2645E-08 Step =
> >
> > The default limit is 1.0 x 10^-8 on energy and it got to 1.013 x 10^-8 so
> > it
> > was REAL close. You could try running the initial part of your heating /
> > equilibration with scfconv=1.0e-7. This will not give as good forces but
> > may
> > be enough to get you away from a high energy starting structure and then
> > you
> > can tighten the convergence back up again later.
> >
> > Good luck,
> > Ross
> >
> >
> > /\
> > \/
> > |\oss Walker
> >
> > | Assistant Research Professor |
> > | San Diego Supercomputer Center |
> > | Tel: +1 858 822 0854 | EMail:- ross.rosswalker.co.uk |
> > | http://www.rosswalker.co.uk | http://www.wmd-lab.org/ |
> >
> > Note: Electronic Mail is not secure, has no guarantee of delivery, may not
> > be read every day, and should not be used for urgent or sensitive issues.
> >
> >
> >
> >
> >
> >
> > _______________________________________________
> > AMBER mailing list
> > 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
--
M. L. Dodson
Business Email: activesitedynamics-at-comcast-dot-net
Personal Email: mldodson-at-comcast-dot-net
Phone: eight_three_two-56_three-386_one
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Wed Mar 31 2010 - 07:00:05 PDT
