Re: AMBER: Gas-phase energies (and more)

From: Jason K <>
Date: Fri, 26 Jan 2007 21:36:25 +0000

Dear Yong (and everyone else who might be reading this),

Thank you very much for your fast reply.

The truth is that I am only using the R(+)-A4 pentapeptide as a test system
because sufficient data using experimental techniques very similar to ours
have been published. What I am actually interested to investigate (in very
few words) is the stability of particular conformations of peptides in
different environments (vacuum, organic solvents and water, the latter being
either implicitly or explicitly simulated). The systems that I simulate
range from 20 to 50 amino acids, and the total simulation time amounts to
several hundreds of nanoseconds. Therefore computational time is an issue. I
must confess however that I have not done any benchmarks on my systems using
polarisable force fields; I suppose this is the next thing to do.
So far I've been running everything using ff99, but I have been thinking for
several months it may be worth switching to "better" parameter sets.

Now, to a few more basic questions...

Are there any "built-in" tools and/or other scripts one would like to share
for performing a potential energy surface scan, so that I could compare
simple PES maps from MM from QM calculations?

If not, could someone point me to the direction of performing MD or energy
minimisation using internal coordinate restraints? Are the options used the
same used for NMR-type restraints?

Finally, does any software exist that can reliably convert from amber
restart (given the parameter file) to internal coordinates (z-matrix) AND
back? I have tried with antechamber, but is generally seems a bit slow (not
surprisingly since it's prime role is parameter fitting and not mere format
conversion) and often crashes out. Furthermore, it does not seem to convert
directly to restart files but only to pdb (a lot of time being spent to
creating unnecessary lists of atom and residue numbers, residue and chain
names) and not always reliable: it worked with the very simple Ace-Ala-Nme
structure, but with my 20-aa-long peptide:

*** glibc detected *** double free or corruption: 0x00000000005a8490 ***
Segmentation fault

and one other time, on a perhaps slightly more exotic heparin molecule it
projected all coordinates to a single axis (!). As far as I know OpenBabel
does not cope with the conversion either, so does anyone know any software
that can do this? I know it is my general ignorance on scripting that is
probably to blame here, yet if there is indeed a script that can be relied
on this conversion, for a system of any size, I would feel very obliged.

[I know that for simple PES scans on small molecules I could extract the
internal coordinates from the gaussian output, convert them into pdb with
babel or newzmat or something similar and finally into rst format, however
this coordinate conversion is a more general problem and the rst to pdb to
zmat to pdb to rst procedure seems quite cumbersome, slow and error-prone].

I do not want this to sound like a criticism, I really appreciate
everybody's help, just some simple issues can take more time than they ought
to. Unfortunately, against a computer I still feel defenseless.

Best Regards,


On 1/25/07, Yong Duan <> wrote:
> Jason,
> Actually the term "gas-phase" or "condensed phase" is somewhat relative.
> Taking your system as an example, if the charges are developed using the
> QM
> esp of the entire molecule, it is probably justified to use gas-phase esp
> if
> the intention is to model its gas-phase behavior, assuming you use
> multiple
> representative conformations in the esp calculation. However, if the
> approach is to obtain the charges of the di-peptides and piece together
> the
> charges for the whole molecule, it is not a clear cut as to how to obtain
> the charges. The reason for this is that, as you might anticipate, the
> peptide (Ace-Arg(+)-Ala-Ala-Ala-Ala-Nme) is sufficiently large that it may
> have tendency to form compact (collapsed) structures, even in gas-phase.
> If
> this is the case, the residues that tend to be burried should perhaps use
> the condensed-phase charges. Intuitively, only those exposed atoms should
> assume gas-phase charges and other atoms should behave like in some sort
> of
> solvent. This is not exactly "hair-splitting". I would say that only the
> fully polarizable force field can do this (or, in a more modest tone, has
> the potential to do the job).
> If you only want to simulate these small peptides in gas-phase, I think
> you
> should use the ff02 charges with polarizability because, theoretically, it
> should be able to deal with it. In fact, if you go through the paper of
> Cieplak et al (JCC paper with Kollman and Caldwell), the charges of ff02
> was
> fitted in gas-phase with polarization. If you are concerned by the added
> cost, simulating such small peptides is really pretty easy these days even
> using the fully polarizable force field.
> As for the torsion parameters, because each torsion parameter set is
> closely
> related to the charges, it makes sense to try Wang et al's torsion
> parameters first. In the work of Wang, the torsion tuning was done in
> gas-phase. In other words, the fitting of the torsion was done by
> comparing
> the di-ala gas-phase energies. But the tests were done in aqueous
> solution.
> So, it should work.
> Hope this helps.
> Good luck!
> yong
> -----Original Message-----
> From: [] On Behalf
> Of
> Jason K
> Sent: Thursday, January 25, 2007 3:04 PM
> To:
> Subject: AMBER: Gas-phase energies (and more)
> Dear AMBER users,
> Much of the research in the group where I work addresses the structures of
> boimolecules in a solvent-free environment. We are trying to reproduce our
> experimental results by molecular mechanical simulations and
> -subsequently-
> the concern that most AMBER parameter sets are tuned to replicate
> condensed-phase energies for small peptides becomes quite relevant. Since
> the electrostatics contribute the most to the energy of the system
> (especially in vacuo), also being the kind of interactions that differ the
> most between the gas phase and solution, I would like to know what
> approach
> I could adopt to generate charge assignments that are more likely to
> mirror
> the electrostatics in the absence of solvent. So far (to partially answer
> my
> own question) I have come across two approaches, (excluding, of course
> re-parameterising the force field in the gas-phase):
> 1) Use the "ff02" residues but with ipol=0 (thus using the "gas phase",
> "static" point-charges). [From what I have gathered, a polarisable force
> field should handle the electrostatics in a vacuum, implicit or explicit
> solvent, at least in theory, but I do not know to what extent this is true
> for the models in AMBER or to what extent they have been tested and hence
> I
> am unwilling to make this assumption]. I am still unsure on whether this
> is
> indeed appropriate, what objections could one raise against using ff02
> charges for gas-phase calculations?
> 2) "Scaling down" the HF/6-31G* charges (by e.g. a factor of 0.8) to
> somewhat relieve the overestimated dipoles. I would be extremely grateful
> if
> someone could tell me how to calculate the partial charges for residues
> with
> non-integer charge. Has this approach been tested?
> Does anyone know any other methods for a "better" representation of
> gas-phase electrostatics of biomolecules?
> Finally, I am bound to ask about other parameters, especially dihedrals.
> Will the tortional terms in parm99.dat or even frcmod.02 (dot
> somethingsomething) drive the peptide away from the "real" gas-phase
> minima?
> I am currently running calculations on a small system
> (Ace-Arg(+)-Ala-Ala-Ala-Ala-Nme) which has been addressed previously and
> see
> which parameter set of the ones available gives "better" energies compared
> with QM, or correspondence with experiment. Yet if anyone could propose me
> a
> different testing method or a more "standard" system, please do so. (The
> reason a protonated peptide is needed is that neutral peptides are not
> directly observable by mass spectrometry and related techniques).
> Thanks in advance
> Jason
> PS1. I haven't read the paper carefully yet, but in Wang et al. J. Comp.
> Chem. (2006) 27(6):781-790 were both the MM and QM calculations performed
> in
> water for the Ace-Ala-Nme dihedral scan ("figure 3") or was the QM done in
> the absence of (implicit) solvation?
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Received on Wed Jan 31 2007 - 06:07:10 PST
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