AMBER Archive (2003)

Subject: Re: AMBER: mgbjsb radii in GBSA

From: Giulio Rastelli (rastelli.giulio_at_unimo.it)
Date: Sat Nov 15 2003 - 11:05:49 CST

> I would like to calculate the binding energy of a protein-ligand
> complex
> using GBSA. I created topologies of ligand, receptor and complex with
> leap,
> setting as default the mgbjsb radii (amber7) to be used with igb=4. The
> ligand
> uses the gaff force field, the protein uses ff99 and the complex uses
> mixed
> gaff+ff99.
> While the GB energies of the receptor and of the complex seem ok, the
> GB
> energy of the ligand is out of scale. I noticed that in the topology
> file
> of the ligand, the first atom has a radius of zero (which explains why
> EGB
> goes out of range) while the others are different from zero. Even if I
> tried only for ten different molecules, it seems that when the first
> atom
> in the prep file belongs to a charged group (eg COO-, NH3+), its radius
> is set to zero. Differently, all atoms have a non-zero radius, and GBSA
> works
> fine.
> I include a prep file of a molecule that did NOT work, as an example.
> Any ideas of why this could happen?
> Thank you very much in advance for your help
>
Here is the point, following a few suggestions I received:
1) using amber atom types instead of gaff atom types give a correct
assignment of mgbjsb radii in the topology file. However please note
that to build the topology I need to set many missing parameters (the
amber force field has much fewer parameters than gaff for organic
molecules). Using parmchk -i lig.prep -f prepi -o frcmod -p parm99.dat
still I have missing parameters (for example it does not recognize CA-HA!)
Since I would like to run mm_pbsa automatically for a set of many
ligands, I cannot manually edit the frcmod file.
2) time ago I posted an example of mm_pbsa calculation which used the
gaff force field and mgbjsb radii, that assigned a radius of zero to the
first atom in the prep file of the ligand. After many tests, I am pretty
inclined to say that there is a bug in the code for assignment of mgbjsb
radii to gaff-atom types (the atom type which had a zero radii was the
carboxyl oxygen o, nothing strange). Bugfix 24 was meant to solve a few
problems regarding lower-case atom types in gaff, and to account for
mbondi radii. I wonder if anybody could also check the code where mgbjsb
radii are read, that would be great!.
3) mbondi radii in mm_pbsa work fine, but as far as I understand,
mm_pbsa was tested only for mgbjsb radii to be used with igb=4. Not
sure, therefore, about the meaning of using mbondi radii, and if I can.

Hoping that somebody will take care of this problem....
thank you very much
Giulio

-----------------------------------------------------------------------
The AMBER Mail Reflector
To post, send mail to amber_at_scripps.edu
To unsubscribe, send "unsubscribe amber" to majordomo_at_scripps.edu