On Thu, Jan 20, 2011 at 5:35 PM, Eric Pettersen <pett.cgl.ucsf.edu> wrote:
> Hi Ross,
> Your points are well taken. If my usage scenario were that of a
> researcher doing an in-depth analysis of the 2ews system I would
> certainly hope to carry out the kinds of sophisticated calculations
> you outline, but that's not my usage scenario. As a developer of
> Chimera I need to use antechamber/sqm to assign not-unreasonable
> partial charges to these kinds of molecules so that systems can be
> prepared in a semi-automated fashion for docking runs or written out
> as prmtop files or used directly in Chimera's minimizer (which
> currently used MMTK but for which we hope to develop a Python
> interface to Amber's SFF routines soon), etc.
>
(yay python)
> My hope, of course, is that something is better than nothing, at
> least for the kind of users that could not possibly hope to carry out
> ab initio calculations to get a more exact answer without at least
> many additional months of effort. And of course for certain kinds of
> bulk calculations such an approach is infeasible anyway.
> If it turns out that sqm simply cannot perform the charge
> computation
> on something like an ionized ATP molecule then I may have to use
> "charge templates" for such molecules as much as possible, like
> Chimera already does for amino/nucleic acids and water. Perhaps using
> values from the "AMBER parameter database" (
> http://www.pharmacy.manchester.ac.uk/bryce/amber
> ) or some such. Maybe I should do the latter anyway for ionized ATP/
> ADP/GTP/GDP (which is the only form in the database) -- any opinion on
> whether the database charges are comparable or better than the
> corresponding (successful) sqm computation?
>
I would say the database charges from the website you cited is almost
certainly better than what you'll get from antechamber/sqm (depending, of
course, on the competency with which they were created). I think most, if
not all, of those parameters are RESP fits using ab-initio calculations, the
typical Amber recipe being HF/6-31G* (perhaps adding diffuse functions for
anions). Add this to the previous comments regarding the struggles that
antechamber/sqm has with these molecules, I would say that if a database
entry exists, that's a better option.
>From a coding perspective, a generic solution is certainly more elegant, but
for such systems perhaps you'll have to settle for less elegance.
My 1cent (graduate student advice/opinion is never worth has much as
Faculty's, at least on paper :) ),
All the best,
Jason
>
> --Eric
>
> On Jan 20, 2011, at 12:28 PM, Ross Walker wrote:
>
> > Hi Eric,
> >
> > Just to add my comments to this discussion.
> >
> >> Thanks for looking into this. I have noticed that many sqm SCF
> >> failures occur with ligands that include phosphate groups, which is
> >> in
> >> line with your observation of SCF convergence difficulties with
> >> highly
> >> negatively charged structures.
> >> The ANP structure in the context of the 2ews PDB entry doesn't
> >> really
> >> allow for the "optimized" geometry delivered by mopac with it's
> >> internal H-bonds to the phosphates, since in 2ews those phosphates
> >> are
> >> occupied by H-bonding to the protein backbone and coordinating a
> >> magnesium ion. Unfortunately sqm couldn't possibly run on ANP in the
> >> larger context of the entire 2ews system, where the negative
> >> phosphate
> >> charges would be stabilized by ANP's environment. Maybe if the
> >> magnesium ion had been included in the sqm input (with the
> >> appropriate
> >> formal charge change) it would have worked?
> >> Anyway, here's hoping for a trickier sqm sometime in the future!
> > :-)
> >
> > I would suggest that you take a step back for a second and consider
> > what you
> > are actually asking for here. You are running the ligand in gas
> > phase and
> > yet somehow suggesting that you actually want the behavior in the
> > protein
> > but you do not want to include the protein. Unfortunately to quote an
> > overused saying, there is no such thing as a free lunch. What you are
> > attempting to do, particularly with phosphates, is notoriously hard.
> > I would
> > suggest going back to the drawing board and considering how you
> > might run
> > the calculations you want with the steric environment of the protein
> > somehow
> > included. What you have is certainly a problem case and you will not
> > be able
> > to treat it in a simple naïve fashion. Chances are you have
> > significant
> > electronic exchange with the protein which makes it unreasonable to
> > consider
> > the charged phosphate system as it is in isolation. You are probably
> > well
> > outside the scope of semi-empirical so I would suggest considering
> > something
> > more rigorous such as an ab initio approach. Certainly it is probably
> > unreasonable to assume that simple AM1-BCC can be applied to complex
> > highly
> > charged systems like phosphates.
> >
> > Think about how you might be able to include the protein environment
> > in the
> > calculation. Possibly fixing the geometry of the surrounding
> > residues and
> > capping them in a consistent fashion, for example with ACE and NME
> > caps.
> > Whatever you end up doing you will need to be consistent and be
> > prepared to
> > defend the choices you made under review. You may also want to
> > carefully
> > check the literature to see what people have done in the past for
> > similar
> > systems.
> >
> > I am sorry if this is not the answer you wanted but I think you are
> > well
> > outside of what Antechamber / SQM are capable of handling in an
> > automated
> > fashion.
> >
> > All the best
> > Ross
> >
> > /\
> > \/
> > |\oss Walker
> >
> > ---------------------------------------------------------
> > | Assistant Research Professor |
> > | San Diego Supercomputer Center |
> > | Adjunct Assistant Professor |
> > | Dept. of Chemistry and Biochemistry |
> > | University of California San Diego |
> > | NVIDIA Fellow |
> > | http://www.rosswalker.co.uk | http://www.wmd-lab.org/ |
> > | Tel: +1 858 822 0854 | EMail:- ross.rosswalker.co.uk |
> > ---------------------------------------------------------
> >
> > 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.
> >
> >
> >
> >
> >
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> >
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--
Jason M. Swails
Quantum Theory Project,
University of Florida
Ph.D. Graduate Student
352-392-4032
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Received on Thu Jan 20 2011 - 15:00:07 PST
