joelib-devel

[Joelib-devel] LogP and MolarRefractivity

[<chr...@ba...>]

Hi all,

I have a question regarding the descriptors LogP and MolarRefractivity:

If I calculate these descriptors for the molecule Oc1ccccc1OC  (which is also
used
in the class GroupContributionTest) using a 3D-structure (see file "tst.sdf"
attached at the end of the mail)
with the command:

convert.sh +d tst.sdf

I get the following wrong results:

>  <MolarRefractivity>
4.3751E1
>  <LogP>
2.2822


But if I delete all H-Atoms by using:
convert.sh -h +d tst.sdf

I get the following results,
which are correct according to the information in GroupContributionTest:

>  <MolarRefractivity>
3.46588E1
>  <LogP>
1.4007999999999998

My question is: Why do I get the wrong results, if I do not delete the H-Atoms?
Do I am on the save side, if I always delete H-Atoms when using a
group contribution method??
(For the "PolarSurfaceArea" it seems, that it doesn't matter if I use "-h" or
not.....)

(By the way, I've used version 2003-08-04)

All the best and thank you very much in advance,
Christoph Niederalt
_________________________________________
Bayer Technology Services GmbH
PT-AS-CS
Leverkusen, K  9
Tel.: +49 (0)214 30 75414
Fax:  +49 (0)214 30 64801
E-Mail:  chr...@ba...
Internet :  http://www.bayertechnology.com

tst.sdf:
===snip===
Model1
  Cerius2 01120415373D 1   1.00000
Structure written by MSI Cerius2 SD Exporter
 17 17  0  0  0  0  0  0  0  0999 V2000
    1.0524   -1.7053   -0.0293 C   0  0  0  0  0  0
    2.1287   -1.6085   -0.0417 H   0  0  0  0  0  0
    0.2023   -0.5743    0.0099 C   0  0  0  0  0  0
    0.6723    0.7567    0.0358 O   0  0  0  0  0  0
   -1.1895   -0.7709    0.0242 C   0  0  0  0  0  0
   -2.0332    0.3430    0.0629 O   0  0  0  0  0  0
   -1.7189   -2.0726   -0.0001 C   0  0  0  0  0  0
   -2.7901   -2.2293    0.0108 H   0  0  0  0  0  0
   -0.8683   -3.1781   -0.0387 C   0  0  0  0  0  0
   -1.2814   -4.1784   -0.0573 H   0  0  0  0  0  0
    0.5140   -2.9945   -0.0532 C   0  0  0  0  0  0
    1.1714   -3.8540   -0.0831 H   0  0  0  0  0  0
    2.0823    0.9796    0.0217 C   0  0  0  0  0  0
   -3.0188    0.1062    0.0707 H   0  0  0  0  0  0
    2.2712    2.0723    0.0457 H   0  0  0  0  0  0
    2.5572    0.5287    0.9194 H   0  0  0  0  0  0
    2.5320    0.5731   -0.9095 H   0  0  0  0  0  0
  1  2  1  0  0  0
  1  3  1  0  0  0
  1 11  2  0  0  0
  3  4  1  0  0  0
  3  5  2  0  0  0
  4 13  1  0  0  0
  5  6  1  0  0  0
  5  7  1  0  0  0
  6 14  1  0  0  0
  7  8  1  0  0  0
  7  9  2  0  0  0
  9 10  1  0  0  0
  9 11  1  0  0  0
 11 12  1  0  0  0
 13 15  1  0  0  0
 13 16  1  0  0  0
 13 17  1  0  0  0
M  END
$$$$

Re: [Joelib-devel] LogP and MolarRefractivity

[Joerg K. W. <we...@in...>]

Hi Christoph,

wrong ... mmhh ... depends on the standpoint of the observer. You surely 
know, and this is still an 'small' actual problem for JOELib and 
OpenBabel and a 'big' problem for all NOT-OPENSOURCE programs. Which 
means: The descriptor calculation process depends on four different 
expert systems (aromaticity, hybridization, implicite valence and 
finally atom type). See:
http://www-ra.informatik.uni-tuebingen.de/software/joelib/tutorial/atomtyper.html
and actual discussions:
http://sourceforge.net/mailarchive/message.php?msg_id=6905792
http://sourceforge.net/mailarchive/forum.php?thread_id=3732947&forum_id=3042

Mostly all ALL descriptors depends on the assigned atom type, so the 
result for each descriptors will change for each other program, because 
most of them have their own atomTyper. JOELib and OpenBabel uses the 
same and are OpenSource, but there is still room for improvement to be 
more general.
So the group contribution definitions are
joelib\src\joelib\data\plain\LogP.contributions
joelib\src\joelib\data\plain\MR.contributions
joelib\src\joelib\data\plain\PSA.contributions

If you use hydrogens from other programs, they will be used to assign 
the SMART patterns, if you remove the hydrogens, JOELib/OpenBabel will 
calculate the implicite hydrogen count on its own, which is, taking my 
descriptor calculation experience into account, really good.
For the definition of the SMARTS group parts see original literature 
reference for these definitions or ask Stephen Jelfs (Gillet/Willet 
group) for more details, because he has implemented this algorithm.
s....@sh...

Furthermore, you surely know that the LogP is not really good, i've once 
ago published a paper about LogP/LogS prediction and this LogP was one 
of the worst, although my models were overfitted (can be seen in actual 
accepted papers, available in 2-3 weeks). See publication section:
http://www-ra.informatik.uni-tuebingen.de/mitarb/wegner

So yes, i recommend to remove all hydrogens, until no general public 
definition FOR ALL PROGRAMS is available ... see mailing list discussion 
above.
Often people believe that descriptors are program independent. 
Especially taking into account that descriptors depends on a complex 
atom assignment process this IS JUST WRONG !!! I complain this in my two 
actual papers and this is actually one of the big problems.

So i believe, that nearly all descriptor calculation programs produce 
different results (most use their own atom typer), even if the 
descriptor calculation algorithm is exactly the same, which is also not 
always true.

Regards, Joerg


> I have a question regarding the descriptors LogP and MolarRefractivity:
> 
> If I calculate these descriptors for the molecule Oc1ccccc1OC  (which is also
> used
> in the class GroupContributionTest) using a 3D-structure (see file "tst.sdf"
> attached at the end of the mail)
> with the command:
> 
> convert.sh +d tst.sdf
> 
> I get the following wrong results:
> 
> 
>> <MolarRefractivity>
> 
> 4.3751E1
> 
>> <LogP>
> 
> 2.2822
> 
> 
> But if I delete all H-Atoms by using:
> convert.sh -h +d tst.sdf
> 
> I get the following results,
> which are correct according to the information in GroupContributionTest:
> 
> 
>> <MolarRefractivity>
> 
> 3.46588E1
> 
>> <LogP>
> 
> 1.4007999999999998
> 
> My question is: Why do I get the wrong results, if I do not delete the H-Atoms?
> Do I am on the save side, if I always delete H-Atoms when using a
> group contribution method??
> (For the "PolarSurfaceArea" it seems, that it doesn't matter if I use "-h" or
> not.....)
> 
> (By the way, I've used version 2003-08-04)
> 
> All the best and thank you very much in advance,
> Christoph Niederalt
> _________________________________________
> Bayer Technology Services GmbH
> PT-AS-CS
> Leverkusen, K  9
> Tel.: +49 (0)214 30 75414
> Fax:  +49 (0)214 30 64801
> E-Mail:  chr...@ba...
> Internet :  http://www.bayertechnology.com
> 
> tst.sdf:
> ===snip===
> Model1
>   Cerius2 01120415373D 1   1.00000
> Structure written by MSI Cerius2 SD Exporter
>  17 17  0  0  0  0  0  0  0  0999 V2000
>     1.0524   -1.7053   -0.0293 C   0  0  0  0  0  0
>     2.1287   -1.6085   -0.0417 H   0  0  0  0  0  0
>     0.2023   -0.5743    0.0099 C   0  0  0  0  0  0
>     0.6723    0.7567    0.0358 O   0  0  0  0  0  0
>    -1.1895   -0.7709    0.0242 C   0  0  0  0  0  0
>    -2.0332    0.3430    0.0629 O   0  0  0  0  0  0
>    -1.7189   -2.0726   -0.0001 C   0  0  0  0  0  0
>    -2.7901   -2.2293    0.0108 H   0  0  0  0  0  0
>    -0.8683   -3.1781   -0.0387 C   0  0  0  0  0  0
>    -1.2814   -4.1784   -0.0573 H   0  0  0  0  0  0
>     0.5140   -2.9945   -0.0532 C   0  0  0  0  0  0
>     1.1714   -3.8540   -0.0831 H   0  0  0  0  0  0
>     2.0823    0.9796    0.0217 C   0  0  0  0  0  0
>    -3.0188    0.1062    0.0707 H   0  0  0  0  0  0
>     2.2712    2.0723    0.0457 H   0  0  0  0  0  0
>     2.5572    0.5287    0.9194 H   0  0  0  0  0  0
>     2.5320    0.5731   -0.9095 H   0  0  0  0  0  0
>   1  2  1  0  0  0
>   1  3  1  0  0  0
>   1 11  2  0  0  0
>   3  4  1  0  0  0
>   3  5  2  0  0  0
>   4 13  1  0  0  0
>   5  6  1  0  0  0
>   5  7  1  0  0  0
>   6 14  1  0  0  0
>   7  8  1  0  0  0
>   7  9  2  0  0  0
>   9 10  1  0  0  0
>   9 11  1  0  0  0
>  11 12  1  0  0  0
>  13 15  1  0  0  0
>  13 16  1  0  0  0
>  13 17  1  0  0  0
> M  END
> $$$$
> 
> 
> 
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-- 
Dipl. Chem. Joerg K. Wegner
Center of Bioinformatics Tuebingen (ZBIT)
Department of Computer Architecture
Univ. Tuebingen, Sand 1, D-72076 Tuebingen, Germany
Phone: (+49/0) 7071 29 78970
Fax: (+49/0) 7071 29 5091
E-Mail: mailto:we...@in...
WWW:    http://www-ra.informatik.uni-tuebingen.de
--
Never mistake motion for action.
                          E. Hemingway