Hi Jason,
Well, I don't exactly know how small/big a molecule should be to be
considered medium. To give you an idea the taxol derivative that I am
working with has 147 atoms without hydrogen atoms added.
-Matt
On Wed, Nov 2, 2011 at 5:36 PM, Jason Swails <jason.swails.gmail.com> wrote:
> As far as I know, taxol is a small-to-medium organic molecule, correct? If
> it's just an isolated ligand, it's probably OK to just use antechamber to
> derive your charges and use the gaff force field to parametrize the
> molecule. You may want to do some dynamics of the isolated ligand to make
> sure that the dynamics "makes sense" (that is, *stupid* conformations are
> not visited), particularly looking at some of the tricky dihedrals (since
> that's what gaff does the worst for). From the looks of it, most of the
> atoms are parts of loops, which tend to be decently forgiving in terms of
> bad dihedrals (since a ring is so restrictive), so you may only have to
> monitor a couple dihedral angles closely.
>
> These dynamics should be very fast (and you can just run it on your
> computer locally).
>
> If it's covalently bound to an amino acid, you may want to try using R.E.D.
> tools or something similar to build an internal residue (similar to the
> first link you sent). Otherwise, it's more like sustiva, and you can use
> the second approach.
>
> HTH,
> Jason
>
> On Wed, Nov 2, 2011 at 5:23 PM, Matthew D Antalek
> <mantale1.binghamton.edu>wrote:
>
> > Hi Jason,
> >
> > Sorry about not getting back sooner about this issue. I've tried to do
> > some research on my own and try and figure out how to fix these problems,
> > but again I'm not sure what to do. For the sake of someone reading this
> > email in an archive, I'll try my best to explain exactly what is going
> on.
> >
> > So my project involves running MD simulations on tubulin with some
> > paciltaxel derivatives. What I did initially was download the 1JFF
> tubulin
> > protein structure from pdb.org and then edited the taxol molecule (in
> the
> > Accelrys visualizer) that came in the 1JFF structure so that I was
> working
> > with the exact taxol derivative that I needed. I then naievely loaded the
> > new pdb file into xLEaP and tried to create a prmtop and inpcrd file, but
> > this failed because I hadn't set the necessary Amber parameters in the
> new
> > taxol residue (which is named TA1). There are also a few other
> non-standard
> > residues that come with the 1JFF struture, but luckily someone else at my
> > institution has provided me with the necessary library and frcmod files.
> >
> > Now I realized that I needed to set the parameters. I was initally trying
> > to use this tutorial:
> > http://ambermd.org/tutorials/advanced/tutorial1/section1.htm, but I also
> > found this tutorial:
> >
> >
> http://www.rosswalker.co.uk/tutorials/amber_workshop/Tutorial_five/create_prmtop.htm
> > .
> > In both tutorials, the prmtop and inpcrd files are created for sustiva,
> but
> > it seems that in the first tutorial, the charges were calculated (which I
> > could do since I have a WebMo account at UB) and in the second tutorial
> > everything was done with antechamber. My question now is what should I be
> > doing?
> >
> > -Matt
> >
> > On Sat, Oct 29, 2011 at 6:52 PM, Jason Swails <jason.swails.gmail.com
> > >wrote:
> >
> > > A couple questions. What is TA1? Why did you load it into Accelrys?
> If
> > > it was just to add hydrogen atoms, leap will do that for standard amino
> > > acids.
> > >
> > > If it turns out that TA1 is a new residue, you'll need to create a new
> > PDB
> > > file from *just* the TA1 atoms (you can cut-and-paste from your big PDB
> > > file into a new PDB file, no need to re-number), and run just that PDB
> > > through antechamber (and parmchk) to get charges and parameters. Then,
> > > load those along with your force field when you build your parameter
> file
> > > in leap.
> > >
> > > The tutorial here: http://ambermd.org/tutorials/advanced/tutorial1/ is
> > > probably most applicable to your problem.
> > >
> > > HTH,
> > > Jason
> > >
> > > On Sat, Oct 29, 2011 at 6:12 PM, Matthew D Antalek
> > > <mantale1.binghamton.edu>wrote:
> > >
> > > > Jason,
> > > >
> > > > Thank you for the explanation. When I first load the pdb file into
> > > tleap,
> > > > I get the following output:
> > > >
> > > > ......
> > > > Created a new atom named: H485 within residue: .R<TA1 844>
> > > > Created a new atom named: H487 within residue: .R<TA1 844>
> > > > Created a new atom named: H489 within residue: .R<TA1 844>
> > > > Created a new atom named: H491 within residue: .R<TA1 844>
> > > > Created a new atom named: H493 within residue: .R<TA1 844>
> > > > Created a new atom named: H495 within residue: .R<TA1 844>
> > > > Created a new atom named: H497 within residue: .R<TA1 844>
> > > > Created a new atom named: H499 within residue: .R<TA1 844>
> > > > Created a new atom named: H501 within residue: .R<TA1 844>
> > > > Created a new atom named: H503 within residue: .R<TA1 844>
> > > > Created a new atom named: H505 within residue: .R<TA1 844>
> > > > Created a new atom named: H507 within residue: .R<TA1 844>
> > > > Created a new atom named: H509 within residue: .R<TA1 844>
> > > > Created a new atom named: H511 within residue: .R<TA1 844>
> > > > Created a new atom named: H513 within residue: .R<TA1 844>
> > > > Created a new atom named: H515 within residue: .R<TA1 844>
> > > > Created a new atom named: H517 within residue: .R<TA1 844>
> > > > Created a new atom named: H519 within residue: .R<TA1 844>
> > > > Created a new atom named: H521 within residue: .R<TA1 844>
> > > > Created a new atom named: H523 within residue: .R<TA1 844>
> > > > total atoms in file: 13333
> > > > Leap added 1864 missing atoms according to residue templates:
> > > > 2 Heavy
> > > > 1799 H / lone pairs
> > > > 63 unknown element
> > > > The file contained 2238 atoms not in residue templates
> > > >
> > > > I then try to save the amber parameter files and I get the following
> > > > output:
> > > >
> > > > ...
> > > > FATAL: Atom .R<TA1 844>.A<H465 229> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H467 230> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H469 231> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H471 232> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H473 233> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H475 234> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H477 235> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H479 236> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H481 237> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H483 238> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H485 239> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H487 240> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H489 241> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H491 242> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H493 243> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H495 244> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H497 245> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H499 246> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H501 247> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H503 248> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H505 249> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H507 250> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H509 251> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H511 252> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H513 253> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H515 254> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H517 255> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H519 256> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H521 257> does not have a type.
> > > > FATAL: Atom .R<TA1 844>.A<H523 258> does not have a type.
> > > > Failed to generate parameters
> > > > Parameter file was not saved.
> > > >
> > > >
> > > > I'm guessing that I'm getting these errors because of the 63 "unknown
> > > > elements" and the "atoms not in residue templates" when I loaded the
> > pdb
> > > > file. Is this just from Accelyrs, or is it because there was some
> other
> > > > error in the file?
> > > >
> > > > Thanks,
> > > > Matt
> > > >
> > > >
> > > >
> > > > On Sat, Oct 29, 2011 at 6:03 PM, Jason Swails <
> jason.swails.gmail.com
> > > > >wrote:
> > > >
> > > > > Hi Matt,
> > > > >
> > > > > Antechamber is designed to derive charges for a small ligand that
> > docks
> > > > in
> > > > > a protein, not an entire protein. It runs a semi-empirical quantum
> > > > > mechanical calculation to determine the charge density around the
> > > > molecule,
> > > > > and then fits partial charges to match that electrostatic
> potential,
> > > more
> > > > > or less. QM calculations are quite expensive, and they're never
> run
> > on
> > > > > full proteins to determine charges. They're run on small compounds
> > and
> > > > > single amino acid/nucleic acid residues to define charges for that
> > > > residue,
> > > > > which are then used on full proteins. As the error message
> suggests,
> > > > > antechamber will not work for full proteins, as that's not what it
> > was
> > > > > designed for.
> > > > >
> > > > > My guess is that Accelrys messed up some of the atom and/or residue
> > > > naming
> > > > > in your PDB which prevents leap from recognizing your structure.
> The
> > > > only
> > > > > time you should need to run antechamber (or get other parameters)
> is
> > > when
> > > > > you have non-standard amino acids or other small organic molecules
> in
> > > > your
> > > > > structure. All other residues (standard amino acids and nucleic
> acid
> > > > > residues) should have their parameters already defined in existing
> > > > > parameter sets (including parameters and partial charges).
> > > > >
> > > > > If you print out the full error you're getting on the first step,
> we
> > > may
> > > > be
> > > > > able to help more.
> > > > >
> > > > > HTH,
> > > > > Jason
> > > > >
> > > > > On Sat, Oct 29, 2011 at 5:51 PM, Matthew D Antalek
> > > > > <mantale1.binghamton.edu>wrote:
> > > > >
> > > > > > Hi all,
> > > > > >
> > > > > > I modified the 1JFF structure from pdb.org using Acclerys, and
> > > saved
> > > > > the
> > > > > > structure as a pdb file. I then loaded the file into leap and
> tried
> > > to
> > > > > > generate the prmtop and inpcrd file but i was getting "FATAL"
> > errors
> > > > when
> > > > > I
> > > > > > tried to save. So I figured it was because there were some
> > parameters
> > > > > > missing or LEaP wasn't recognizing some of the atoms. Then I
> tried
> > to
> > > > > > follow
> > > > > > the steps on this tutorial to try and use antechamber to fix the
> > pdb
> > > > > file,
> > > > > > but I got more errors.
> > > > > >
> > > > > >
> > > > > > Warning: detected more than 10 Residue sequence numbers;
> > > > > > this may be a large multiple residue PDB file;
> > > > > > large multiple residue PDB files are not supported.
> > > > > > Continuing, but problems may be encountered.
> > > > > > The atom number exceeds the MAXATOM, reallocate memory
> > > > > > Info: the bond number exceeds MAXBOND, reallocate memory
> > > automatically
> > > > > >
> > > > > > Error: cannot run "/home/matthew/amber11/bin/bondtype -j full -i
> > > > > > ANTECHAMBER_BOND_TYPE.AC0 -o ANTECHAMBER_BOND_TYPE.AC -f ac" in
> > > > > > judgebondtype() of antechamber.c properly, exit
> > > > > > [matthew.matt-pc octMD]$
> > > > > >
> > > > > >
> > > > > > I got the initial "warning" message many many times. If anyone
> > knows
> > > if
> > > > > > there is something that must be done for large pdb files or if
> > anyone
> > > > > knows
> > > > > > of a good antechamber tutorial, please let me know.
> > > > > >
> > > > > > Sincerely,
> > > > > > Matt Antalek
> > > > > > _______________________________________________
> > > > > > AMBER mailing list
> > > > > > AMBER.ambermd.org
> > > > > > http://lists.ambermd.org/mailman/listinfo/amber
> > > > > >
> > > > >
> > > > >
> > > > >
> > > > > --
> > > > > Jason M. Swails
> > > > > Quantum Theory Project,
> > > > > University of Florida
> > > > > Ph.D. Candidate
> > > > > 352-392-4032
> > > > > _______________________________________________
> > > > > 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
> > > >
> > >
> > >
> > >
> > > --
> > > Jason M. Swails
> > > Quantum Theory Project,
> > > University of Florida
> > > Ph.D. Candidate
> > > 352-392-4032
> > > _______________________________________________
> > > 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
> >
>
>
>
> --
> Jason M. Swails
> Quantum Theory Project,
> University of Florida
> Ph.D. Candidate
> 352-392-4032
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
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Received on Wed Nov 02 2011 - 15:00:04 PDT
