AMBER Archive (2007)

Subject: Re: AMBER: antechamber fails with large molecules

From: Ilyas Yildirim (yildirim_at_pas.rochester.edu)
Date: Sat Nov 03 2007 - 10:47:49 CST

Dear Francesco,

Can you send me the .pdb structure of that molecule? I am curious on how
it looks like.

Regards,

On Sat, 3 Nov 2007, Francesco Pietra wrote:

> Hi Ilyas:
> That molecule of 500 atoms was a bold starting at a time that I knew even less
> than I know now. I mentioned that in the context of the new respgen.c only to
> remind my interest. Set aside. There is no theory to deal computationally with
> that.
>
> What you are saying (and other subscribers said in parallel interventions) does
> not apply to organic chemistry/natural product chemistry, except perhaps in
> rare out-of-the-norm cases, if any. At any event, I am not aware of any single
> example of treating a complicated organic molecule as residues to be recomposed
> later. The reason is simple: any portion is generally highly flexible - which
> defeats any choice of residues - and any portion you can conceive interacts
> strongly with neighboring portions. No repetitive units, very scarce similarity
> with units in other families of compounds, and a behavior that depends on large
> sections of the molecule, if not, in many cases, on the whole. That is
> certainly the case of my 500-atoms molecule, and even of the other smaller
> members of the family.
>
> This is why computational medicinal chemists do docking for very small - or
> very rigid - ligands only. Nonetheless, nature is able to dock specifically
> with molecules as alrge and as flexible as above.
>
> Perhaps one could calculate partial charges rapidly with antechamber (not for
> 500-atoms molecule, say 150-atoms) carry out a simulated annealing and/or a
> montecarlo sampling and then refining by calculating the partial charges for a
> wide variety of low-energy conformers. Finally, averaging.
>
> regards
> francesco
>
>
>
> --- Ilyas Yildirim <yildirim_at_pas.rochester.edu> wrote:
>
> > In these papers, they deal with POPC molecule and calculate the resp
> > charges for POPC so that they can form a 128 POPC bilayer structure. They
> > choose 12 conformations for POPC and they show that with this choice, they
> > can predict some of the experimental results. Whether 12 is enough or not,
> > I do not know. I am sure they have their reasons on why they have chosen
> > 12 conformations for POPC.
> >
> > It is, still, following the resp protocol, though I am not sure how they
> > followed the resp protocol. POPC looks more complicated than an RNA
> > nucleotide, but it is still possible to follow the resp protocol to
> > calculate the charges. After the resp charge calculation for POPC, they
> > create the molecule which has 128 POPC in it.
> >
> > So, for a 500 atom system, can you calculate the resp charges? Quantum
> > Mechanical optimization can take forever for this system. If you want to
> > stick with fixed charge method, you have to divide your structure into sub
> > structures. Dr. SantaLucia's group created a database for modified RNA
> > nucleotides.
> >
> > http://ozone3.chem.wayne.edu:8080/Modifieds/jsps/move.jsp#
> >
> > In their paper (Aduri, R., Psciuk, B. T., Saro, P., Taniga, H., Schlegel,
> > H. B., SantaLucia, J., Jr. (2007) "AMBER Force Field Parameters for the
> > Naturally Occurring Modified Nucleosides in RNA", J. Chem. Theory and
> > Comput., 3, 1464 -1475.), they explain how they calculated the resp
> > charges. For some big complicated nucleotides, they made some
> > approximations such as diving that particular nucleotide into 2 parts; one
> > is the sugar part and the other one is the base part. They optimize and
> > calculate the resp charges of these two parts seperately. At the end, they
> > combine these two parts to create the library file for that particular
> > complicate nucleotide.
> >
> > So, even though you cannot calculate the resp charges for a 500 atom
> > system directly, you can make approximation by diving the structure into
> > small segments and calculate the resp charges for those segments
> > seperately. At the end, you can combine the resp charges to create your
> > library file for 500 atom system. How to divide your structure into
> > sub segments/structures depend on how your structure looks like. The most
> > important point of these sub segments should be that they should not
> > interact with each other crucially (at least the interaction should not be
> > too big). For instance, in an RNA nucleotide, you can divide the
> > nucleotide into sugar + base because the interaction between these two is
> > not too big (at least that is what the approximation is in some of the
> > resp calculations in the above database).
> >
> > By the way, when you use antechamber to get the charges, they won't be
> > the resp charges.
> >
> > Best,
> >
> > On Fri, 2 Nov 2007, Francesco Pietra wrote:
> >
> > > Hopefully polarizable force fields will put - they alone - the house in
> > order.
> > > I doubt, simply because it seems too good.
> > >
> > > People using the fixed charge strategy have long devised to mediate between
> > > conformers. A very careful piece of work to this regard came recently from
> > > Hungary, concerning the POPC lipidic double layer (J Comput Chem 2007, 28,
> > > 2051-8). Is such type of huge work absolutely needed routinely? Other
> > groups -
> > > in the context of hugh-level publication - still treat the same POPC with
> > fixed
> > > charges for a single conformer (JACS 2007, 129, 6970-1). Surely, it depends
> > on
> > > the precision to attain. My conformers, plagued by huge degrees of freedom
> > and
> > > differing in energy by 1 kcal/mol, can't be treated computationally in
> > > condensed phase at any level of theory.
> > >
> > > francesco
> > >
> > >
> > > --- Ilyas Yildirim <yildirim_at_pas.rochester.edu> wrote:
> > >
> > > > As I wrote in my previous email, polarizable force fields are still under
> > > > development. In amber99 force field, there is a parameter defined
> > > > as polarizability, but this is for Mg2+ and F- ions. I am not sure how
> > the
> > > > polarizability is implemented to AMBER 9, but I am not aware of a fully
> > > > constructed polarizable force field. Others might know more about this.
> > > >
> > > > Best,
> > > >
> > > > On Fri, 2 Nov 2007, Eddie Men wrote:
> > > >
> > > > > This is a good question (or one I also have):
> > > > >
> > > > > "A better solution might be to use a polarizable force field, which
> > will
> > > > > change the charges of the atoms by time, depending on the neighbouring
> > > > > atoms they are interacting. Polarizable force fields are still in
> > > > > development stage, and I am not aware of any fully working polarizable
> > > > > force field."
> > > > >
> > > > > I tried a model with resp charges for ATP braking it into ADP and PO3,
> > > > > however when computing free energies the ATP breaks spontaneously at
> > > > > very low temperature ( because both molecules are negative charged),
> > > > > so I changed to a QM/MM description.
> > > > >
> > > > > Is it possible to model that reaction with polarizable forece fields?.
> > > > > What about mixing force fields?.
> > > > >
> > > > >
> > > > > Eddie
> > > > >
> > > > >
> > > > > Best,
> > > > >
> > > > >
> > > > > Ilyas Yildirim wrote:
> > > > > > I know this question was discussed before, but I, also, do not
> > > > understand
> > > > > > the reason to calculate the resp charges for a system like a molecule
> > > > > > which has 500 atoms in it. My understanding of charges and its
> > importance
> > > > > > in a structure is as follows:
> > > > > >
> > > > > > Some charge distrubution (point charges in this case) has to be
> > chosen
> > > > > > such that it is going to mimic the Q.M. potential around the
> > molecule.
> > > > > > Currently, constant charges are used in molecules, meaning the
> > charges
> > > > > > do not change by simulation time (except for some polarizable force
> > field
> > > > > > implementations, which is still new). The critical question is this:
> > For
> > > > > > this molecule, is there only one conformation or more than one? If it
> > is
> > > > > > a small molecule, probably it will choose one particular
> > conformation,
> > > > > > which implies that one charge distribution might be reasonable enough
> > to
> > > > > > mimic the quantum mechanical potential around this molecule.
> > > > > >
> > > > > > If the structure is too big, then it will probably have more than one
> > > > > > conformation to choose. Without knowing the conformations this
> > molecule
> > > > > > can choose, a constant charge distribution model will never work. The
> > > > best
> > > > > > thing to do (if someone wants to use constant charge model) is to
> > divide
> > > > > > this molecule into sub-molecules (like residues) and then to
> > calculate
> > > > the
> > > > > > charges for these sub-molecules (this is still an approximation
> > though).
> > > > > >
> > > > > > A better solution might be to use a polarizable force field, which
> > will
> > > > > > change the charges of the atoms by time, depending on the
> > neighbouring
> > > > > > atoms they are interacting. Polarizable force fields are still in
> > > > > > development stage, and I am not aware of any fully working
> > polarizable
> > > > > > force field.
> > > > > >
> > > > > > Best,
> > > > > >
> > > > > > On Thu, 1 Nov 2007, Junmei Wang wrote:
> > > > > >
> > > > > >
> > > > > >> Personally I don't think there is a good approach to get good
> > charges
> > > > (such as HF/6-31G* RESP). AM1BCC may be a good candidate. The problem is
> > that
> > > > antechamber may not handle such large molecules well. In amber10, I have
> > > > improved the code a little bit to handle large molecules much better, in
> > a
> > > > long run I also plan to develop a even simpler, but more reliable charges
> > > > (compared to am1-bcc) for arbitrary organic molecules. This method will
> > be
> > > > available in amber11.
> > > > > >>
> > > > > >> Best
> > > > > >>
> > > > > >> Junmei
> > > > > >>
> > > > > >> ----- Original Message ----
> > > > > >> From: Francesco Pietra <chiendarret_at_yahoo.com>
> > > > > >> To: amber_at_scripps.edu
> > > > > >> Sent: Thursday, November 1, 2007 3:29:26 AM
> > > > > >> Subject: Re: AMBER: antechamber fails with large molecules
> > > > > >>
> > > > > >> You may remeber that I tried unsuccessfully to get the partial
> > charges
> > > > with
> > > > > >> Antechamber in Amber9 for a 500-atoms non-repetitive molecule. Prof
> > > > Case, and
> > > > > >> others, suggested, however, that, even if calculated, the partial
> > > > charges would
> > > > > >> be unreliable for such a large residue.
> > > > > >>
> > > > > >> Is the new code intended to solve this question too?
> > > > > >>
> > > > > >> At any event, do you plan to make the new code available? An when? I
> > > > have
> > > > > >> frequently problems of large ligands.
> > > > > >>
> > > > > >> Thanks
> > > > > >>
> > > > > >> francesco pietra
> > > > > >>
> > > > > >>
> > > > > >> --- Junmei Wang <junmwang_at_yahoo.com> wrote:
> > > > > >>
> > > > > >>
> > > > > >>> Could you send me the file? I have modified the respgen.c code a
> > > > little bit
> > > > > >>> to handle large molecules, but it is not in amber9.
> > > > > >>>
> > > > > >>> Best
> > > > > >>>
> > > > > >>> Junmei
> > > > > >>>
> > > > > >>> Dear amber users:
> > > > > >>>
> > > > > >>> I am trying fit RESP charges with antechamber to a large
> > > > > >>> organic molecule (342 atoms) with the command:
> > > > > >>>
> > > > > >>> antechamber –i biscalix.log –fi gout –o biscalix_resp.mol2
> > > > > >>> -fo mol2 –c resp
> > > > > >>>
> > > > > >>> This fitting process failed with the following errors:
> > > > > >>>
> > > > > >>> “The number of the path atoms exceeds
> > > > > >>> MAXPATHATOMNUM(1900000) for atom[148],extend the size and
> > > > > >>> reallocate the memory automatically reallocate memory for
> > > > > >>> pathscore[148] failed
> > > > > >>> Info: the atom number exceeds the MAXATOM, reallocate
> > > > > >>> memory automatically
> > > > > >>> Amber 9 RESP
> > > > > >>> Unit 5 Error on OPEN: ANTECHAMBER_RESP1.IN
> > > > > >>> Error: cannot run "resp -O -i ANTECHAMBER_RESP1.IN -o
> > > > > >>> ANTECHAMBER_RESP1.OUT -e ANTECHAMBER.ESP -t qout" in
> > > > > >>> resp() of charge.c properly, exit”.
> > > > > >>>
> > > > > >>> Could someone give me any idea about how to solve this
> > > > > >>> type of problems?
> > > > > >>>
> > > > > >>> Thanks in advance,
> > > > > >>> Vânia Calisto
> > > > > >>>
> > > > > >>>
> > > > > >>>
> > > > > >>>
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> > > > --
> > > > Ilyas Yildirim
> > > > ---------------------------------------------------------------
> > > > = Department of Chemistry - =
> > > > = University of Rochester - =
> > > > = Rochester, NY 14627-0216 - Ph.:(585) 275 67 66 (Office) =
> > > > = http://www.pas.rochester.edu/~yildirim/ =
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> > --
> > Ilyas Yildirim
> > ---------------------------------------------------------------
> > = Department of Chemistry - =
> > = University of Rochester - =
> > = Rochester, NY 14627-0216 - Ph.:(585) 275 67 66 (Office) =
> > = http://www.pas.rochester.edu/~yildirim/ =
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-- 
  Ilyas Yildirim
  ---------------------------------------------------------------
  = Department of Chemistry      -                              =
  = University of Rochester      -                              =
  = Rochester, NY 14627-0216     - Ph.:(585) 275 67 66 (Office) =
  = http://www.pas.rochester.edu/~yildirim/                     =
  ---------------------------------------------------------------

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