[gmx-users] Inconsistency in gmx sasa/g_sas buried SASA?

[João M. Damas]

The formula, following your notation, should be (A+B-AB)/2. The value
you're obtaining is the buried area of protein plus the buried area of the
ligand, hence you need to divide it by two.

The remaining differences from the approach [total-area(ligand) -
exposed-area(ligand)] could be due the probe, which "probes" differently in
each approach.

If there are still inconsistencies, please let us know.

Best,
João

On Wed, Mar 4, 2015 at 8:48 PM, Leandro Bortot <leandro.obt at gmail.com>
wrote:

> Dear users,
>
>      I'm trying to calculate how much of a given ligand surface area is
> buried upon binding to a protein.
>      I did it before for two proteins by doing three separate calls of gmx
> sasa, each for the surface and output groups "System" and "System" of files
> containing protein A, protein B and the AB complex. Then, I used to
> calculate the buried area by doing "sasa_A + sasa_B - sasa_AB". However, I
> found some strange values with a protein-ligand system. Can you please
> point me to what I'm doing wrong?
>
>
>      If I follow the previously stated protocol with pdb files of the
> complex, isolated ligand and isolated receptor, I end with the following
> values for the SASAs: 85.8060, 8.288 and 86.4280 nm^2, respectively. By
> doing the "A+B-AB" calculation, I get a buried area of 8.9100 nm^2, which
> is actually more than the whole isolated ligand.
>      On the other hand, by using the -surface and -output groups "System"
> and "Other", I have the value of 2.970 nm^2 of exposed area for the ligand
> in the complex, which corresponds to a buried area of 5.3180 nm^2, 64% of
> the ligand, which seems reasonable according to visual inspection.
>
>      Why are the values calculated by the two approaches not consistent?
>      My first thought was that gmx sasa was not "seeing" the whole ligand
> in the complex structure, hence the very small increment in the complex
> SASA in comparison with the isolated receptor. However, the results for
> using different -surface and -output groups doesn't agree with that.
>      I have the same results with GROMACS 4.6.7 with slightly different
> numerical values, which I assume is due to the changes in the values of
> vdwradii.dat. I get > 100% are buried by doing the "A+B-AB" calculation and
> around 60% when I use "System" and "Other" in g_sas.
>
>      I tried using .gro files created from the .pdb by editconf, but
> nothing changed. I cannot afford to generate the tprs because I'm trying to
> use GROMACS to analyse a large number of complexes which came from a
> virtual screening essay.
>      The .pdb files are typical, there is nothing strange in them. At least
> as much as I can tell.
>
>
>      Here are the commands I used, for clarity.
>
>          gmx sasa -f complex.pdb -s complex.pdb -nopbc -o sasa_complex.xvg
> -surface "System" -output "System" -xvg none -probe 0.14 -ndots 24
>          gmx sasa -f ligand.pdb -s ligand.pdb -nopbc -o sasa_ligand.xvg
> -surface "System" -output "System" -xvg none -probe 0.14 -ndots 24
>          gmx sasa -f receptor.pdb -s receptor.pdb -nopbc -o
> sasa_receptor.xvg -surface "System" -output "System" -xvg none -probe 0.14
> -ndots 24
>          gmx sasa -f complex.pdb -s complex.pdb -nopbc -o
> sasa_difference.xvg -surface "System" -output "Other" -xvg none -probe 0.14
> -ndots 24
>
>
>      Any help is greatly appreciated.
>
> Thank you for your attention,
> Leandro.
> --
> Gromacs Users mailing list
>
> * Please search the archive at
> http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before
> posting!
>
> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>
> * For (un)subscribe requests visit
> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
> send a mail to gmx-users-request at gromacs.org.
>



-- 
João M. Damas
PhD Student
Protein Modelling Group
ITQB-UNL, Oeiras, Portugal
Tel:+351-214469613