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
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Received on Wed Nov 02 2011 - 15:00:03 PDT
