From owner-chemistry@ccl.net Sun Jan 16 00:17:00 2011 From: "Andrew Dalke dalke*dalkescientific.com" To: CCL Subject: CCL: PyMCS - still available? Message-Id: <-43649-110115220440-30685-bwF7yAlEZ5fuJ3+N+q68iQ*o*server.ccl.net> X-Original-From: Andrew Dalke Content-Transfer-Encoding: 8bit Content-Type: text/plain; charset=us-ascii Date: Sun, 16 Jan 2011 04:04:23 +0100 Mime-Version: 1.0 (Apple Message framework v1082) Sent to CCL by: Andrew Dalke [dalke_+_dalkescientific.com] On Jan 13, 2011, at 10:44 AM, Kurt De Grave Kurt.DeGrave|*|cs.kuleuven.be wrote: > The FOG program can compute maximal common subgraphs in polynomial time > -- but only on outerplanar graphs. (It can tell you if one of the graphs > is non-outerplanar, in which case you can fall back to another tool.) > > http://people.cs.kuleuven.be/~jan.ramon/fog/ I looked into this because I've wondered about which types of search can be improved by classifying structures into "easy to search" vs. "hard to search", and using different algorithms as appropriate rather than only using an algorithm which works for the hard case. However, you don't make it easy for people to try out your software: - that URL does not have a download link, which is http://people.cs.kuleuven.be/~jan.ramon/fog/readme.html I found it by reading one of the PDFs - the readme says there is a tests/ subdirectory, but there isn't - the code uses "ushort" and "malloc.h" which aren't portable. I also had to force "CC=g++" in the Makefile in order to compile biconn.c (it's a C++ program with a ".c" extension) - While I have a copy of the NCI data set, and found the -db= option to change the default location for it, I didn't try to reverse engineer the format. It's neither SMILES nor SDF. In what I can read it doesn't appear to handle what PyMCS handled, which is the ability to generate the MCS from a group of compounds. I know that other tools, such as GGA's free Indigo toolkit, have code to solve this problem. My search for PyMCS is mostly emotional. I wrote that code, and I spent about 6 weeks developing it. It was the first non-trivial cheminformatics algorithm I wrote and it was the basis for some of Bioreason's technology. And sadly, no progress on tracking down that code. Best regards, Andrew Dalke dalke!=!dalkescientific.com -- Only a month left to register for my "Python for Cheminformatics" and "Web Applications Development for Cheminformatics" courses. 14-15 and 16-18 February. Leipzig, Germany http://dalkescientific.com/training/ From owner-chemistry@ccl.net Sun Jan 16 02:48:00 2011 From: "Jissy AK jissy!^!iisertvm.ac.in" To: CCL Subject: CCL: Charge Transfer integral calculation Message-Id: <-43650-110116021942-11976-HKmCiUfuy7+mnAxPOfZzNg_._server.ccl.net> X-Original-From: Jissy AK Content-Type: multipart/alternative; boundary=001636c5a4f1d68e460499f17c8e Date: Sun, 16 Jan 2011 12:49:27 +0530 MIME-Version: 1.0 Sent to CCL by: Jissy AK [jissy-x-iisertvm.ac.in] --001636c5a4f1d68e460499f17c8e Content-Type: text/plain; charset=ISO-8859-1 Content-Transfer-Encoding: quoted-printable Thanks Marcel, Yes, I was using an older version of ADF. The feature was introduced in the 2010 version. However, it is still possible to determine the charge transfer integrals from the ADF output of previous versions by using the overlap matrix, eigenvector matrix and the eigenvalue matrix in the fragment orbital basis. Jissy On Thu, Jan 13, 2011 at 8:11 PM, Marcel Swart marcel.swart,,icrea.cat < owner-chemistry:ccl.net> wrote: > > Sent to CCL by: Marcel Swart [marcel.swart]_[icrea.cat] > Hello Jissy, > > questions about ADF might better be asked at the ADF Forum: > http://www.scm.com/forums > > In any case, I've just run the same example, and it gives me exactly > what was to be expected, i.e. both the Overlap Integrals, and the > Site Energies. I'm not sure when this TRANSFERINTEGRALS > feature added, but probably it was introduced in the 2010 release. > (see http://www.scm.com/News/ADF2010.html) > > Probably you are using an older version? > > Marcel > > On Jan 13, 2011, at 11:41 AM, Jissy AK jissy%iisertvm.ac.in wrote: > > > Dear colleagues, > > > > I tried out the "AT base pair: Charge transfer > integrals" example given in ADF. I used exactly the same input files as > given in the example. I got a NORMAL TERMINATION for the jobs, but in the > output file, I did not find the overlap integral or the site energies. So= . > how do I get these values? > > > > Thanks in advance > > > > > > -- > > Jissy AK > > PhD Student > > IISER-TVM > > > > "It is nice to know that the computer understands the problem. But I > > would like to understand it too." -- Eugene P. Wigner > > =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D > dr. Marcel Swart > > ICREA Research Professor at > Institut de Qu=EDmica Computacional > Universitat de Girona > > Facultat de Ci=E8ncies > Campus Montilivi > 17071 Girona > Catalunya (Spain) > > tel > +34-972-418861 > fax > +34-972-418356 > e-mail > marcel.swart ~ icrea.cat > marcel.swart ~ udg.edu > web > http://www.marcelswart.eu > =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D > > > > -=3D This is automatically added to each message by the mailing script = =3D-> > > --=20 Jissy AK PhD Student IISER-TVM "It is nice to know that the computer understands the problem. But I would like to understand it too." -- Eugene P. Wigner --001636c5a4f1d68e460499f17c8e Content-Type: text/html; charset=ISO-8859-1 Content-Transfer-Encoding: quoted-printable Thanks Marcel,

=A0=A0=A0=A0=A0=A0=A0=A0=A0=A0=A0=A0 Yes, I was using= an older version of ADF. The feature was introduced in the 2010 version. H= owever, it is still possible to determine the charge transfer integrals=A0 = > from the ADF output of previous versions by using the overlap matrix, eigen= vector matrix and the eigenvalue matrix in the fragment orbital basis.

Jissy

On Thu, Jan 13, 2011 at 8:11 PM= , Marcel Swart marcel.swart,,icrea.cat <owner-chemist= ry:ccl.net> wrote:

Sent to CCL by: Marcel Swart [marcel.swart]_[icrea.cat]
Hello Jissy,

questions about ADF might better be asked at the ADF Forum:
http://www.scm.com/= forums

In any case, I've just run the same example, and it gives me exactly what was to be expected, i.e. both the Overlap Integrals, and the
Site Energies. I'm not sure when this TRANSFERINTEGRALS
feature added, but probably it was introduced in the 2010 release.
(see htt= p://www.scm.com/News/ADF2010.html)

Probably you are using an older version?

Marcel

On Jan 13, 2011, at 11:41 AM, Jissy AK jissy%iisertvm.ac.in wrote:

> Dear colleagues,
>
> =A0 =A0 =A0 =A0 =A0 =A0 =A0 =A0 =A0I tried out the "AT base pair:= Charge transfer integrals" example given in ADF. I used exactly the s= ame input files as given in the example. I got a NORMAL TERMINATION for the= jobs, but in the output file, I did not find the overlap integral or the s= ite energies. So. how do I get these values?
>
> Thanks in advance
>
>
> --
> Jissy AK
> PhD Student
> IISER-TVM
>
> "It is nice to know that the computer understands the problem. Bu= t I
> would like to understand it too." -- Eugene P. Wigner

=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D
dr. Marcel Swart

ICREA Research Professor at
Institut de Qu=EDmica Computacional
Universitat de Girona

Facultat de Ci=E8ncies
Campus Montilivi
17071 Girona
Catalunya (Spain)

tel
+34-972-418861
fax
+34-972-418356
e-mail
marcel.swart ~ icrea.cat=
marcel.swart ~ udg.edu
web
http://www.marcelsw= art.eu
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D



-=3D This is automatically added to each message by the mailing script =3D-=
E-mail to subscribers: CHEMISTRY:ccl.n= et or use:
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--
Jissy AK
PhD Student=
IISER-TVM

"It is nice to know that the computer understands= the problem. But I
would like to understand it too." -- Eugene P. Wigner
--001636c5a4f1d68e460499f17c8e-- From owner-chemistry@ccl.net Sun Jan 16 03:22:00 2011 From: "Bonoit Bonoit bonoit_10,+,yahoo.fr" To: CCL Subject: CCL: MPn and CBS methods Message-Id: <-43651-110116024323-19239-vIWXtALq11HKvK9kGOehSg#%#server.ccl.net> X-Original-From: "Bonoit Bonoit" Date: Sun, 16 Jan 2011 02:43:22 -0500 Sent to CCL by: "Bonoit Bonoit" [bonoit_10-$-yahoo.fr] Hi cclers, I'm searching a detailed paper on the Moller-Plesset theory (perturbation) and CBS methods. Your help will be appreciated Sincerely, Bonoit From owner-chemistry@ccl.net Sun Jan 16 04:25:00 2011 From: "Andreas Bender bender.andreas~!~gmail.com" To: CCL Subject: CCL: in silico biotargets fishing - reverse screening Message-Id: <-43652-110116042214-854-PQGpG1Rv7ihgw84RWXtJxA(-)server.ccl.net> X-Original-From: Andreas Bender Content-Transfer-Encoding: 8bit Content-Type: text/plain; charset=ISO-8859-1 Date: Sun, 16 Jan 2011 09:21:59 +0000 MIME-Version: 1.0 Sent to CCL by: Andreas Bender [bender.andreas+*+gmail.com] Hi Andrew, There are several methods around to predict protein targets of small molecules, both ligand-based and structure-based ones. One example of the ligand-based approaches is SEA from the Shoichet group (http://sea.bkslab.org/) which is based on fingerprints. Last year also a webtool, PharmMapper, has been published which allows you to predict targets using pharmacophores, the address is http://59.78.96.61/pharmmapper/. So there are the web interfaces, but on the other hand it's also relatively easy to take all the bioactivity data from e.g. ChEMBL and train a multi-class model on fingerprints or any other descriptors you find relevant. A recent review article on the topic has been written by Ma et al., http://www.ncbi.nlm.nih.gov/pubmed/20221898. We also wrote one in 2007 which you can find here: http://dx.doi.org/10.1016/j.ddtec.2006.12.008. Currently I am finishing another review article on the topic, so if you (or anyone else on the list) is interested in receiving a copy when published please just let me know. Best wishes, Andreas -- Andreas Bender, PhD Lecturer for Molecular Informatics Unilever Centre, Cambridge University http://www-ucc.ch.cam.ac.uk Personal: http://www.andreasbender.de On Fri, Jan 14, 2011 at 11:24 AM, Andrew Voronkov drugdesign[]yandex.ru wrote: > > Sent to CCL by: Andrew Voronkov [drugdesign+*+yandex.ru] > Dear CCL users, > I have seen a very interesting presentation from Intelligand on biotargets in silico deconvolution for the known compounds. This is pharmacophore-based screening approach for some sets of biotargets. What are other methods, software and approaches available for in silico biotarget identification for compounds without know targets-mechanisms of action? The best of course would be to find some tools which is possible to use locally? > > > Best regards, > Andrew>      http://www.ccl.net/cgi-bin/ccl/send_ccl_message>      http://www.ccl.net/cgi-bin/ccl/send_ccl_message>      http://www.ccl.net/chemistry/sub_unsub.shtml>      http://www.ccl.net/spammers.txt> > > From owner-chemistry@ccl.net Sun Jan 16 05:00:00 2011 From: "Shirin Seifert shirin.seifert|-|gmail.com" To: CCL Subject: CCL: koopmans' theorem Message-Id: <-43653-110116042937-8988-3rhFGM9xtKC7TtLdP1a14A#server.ccl.net> X-Original-From: Shirin Seifert Content-Type: multipart/alternative; boundary=0016e659fd0875d92e0499f34d9c Date: Sun, 16 Jan 2011 12:59:22 +0330 MIME-Version: 1.0 Sent to CCL by: Shirin Seifert [shirin.seifert : gmail.com] --0016e659fd0875d92e0499f34d9c Content-Type: text/plain; charset=ISO-8859-1 Hi, On using the koopmans' theorem to estimate the first and second ionization energy of a cation, should the geometry of the molecule be that of the cation (but neutral)? or the considered geometry is from the optimized neutral molecule? Thanks for your explanation in advance. Regards, S.S --0016e659fd0875d92e0499f34d9c Content-Type: text/html; charset=ISO-8859-1 Hi,

On using the koopmans' theorem to estimate the first and second ionization energy of a cation, should the geometry of the molecule be that of the cation (but neutral)? or the considered geometry is from the optimized neutral molecule?

Thanks for your explanation in advance.

Regards,
S.S
--0016e659fd0875d92e0499f34d9c-- From owner-chemistry@ccl.net Sun Jan 16 05:35:00 2011 From: "Goedele Roos groos()vub.ac.be" To: CCL Subject: CCL: koopmans' theorem Message-Id: <-43654-110116052132-9557-NNcuKTMm5Hn6Q/U/s6rWsg%a%server.ccl.net> X-Original-From: Goedele Roos Date: Sun, 16 Jan 2011 11:21:18 +0100 Sent to CCL by: Goedele Roos [groos^^^vub.ac.be] Hi, If you would like to know the IE of cation with Koopmanss theorem, take the cation geometry; if you would like to know IE of the neutral molecule, take the geometry of neutral molecule. Best regards, Goedele >Hi, > >On using the koopmans' theorem to estimate the first and second ionization >energy of a cation, should the geometry of the molecule be that of the >cation (but neutral)? or the considered geometry is from the optimized >neutral molecule? > >Thanks for your explanation in advance. > >Regards, >S.S > > _____________________________ Goedele Roos, PhD Department of General Chemistry VIB Department of Molecular and Cellular Interactions | http://www.vib.be/ Structural Biology Brussels, Vrije Universiteit Brussel | http://www.structuralbiology.be/ Brussels Center for Redox Biology | http://redox.vub.ac.be/ Vrije Universiteit Brussel, Building G, room 10G714 Pleinlaan 2, 1050 Brussels,Belgium phone: +32 2 6293312 fax: +32 2 6293317 E-mail: groos|,|vub.ac.be From owner-chemistry@ccl.net Sun Jan 16 06:18:00 2011 From: "Jun Zhang coolrainbow:-:yahoo.cn" To: CCL Subject: CCL: CL: koopmans' theorem Message-Id: <-43655-110116061634-32205-qb1yJAWj7Rhgb94hGf3L3w++server.ccl.net> X-Original-From: Jun Zhang Content-Type: multipart/alternative; boundary="0-738748691-1295176576=:97253" Date: Sun, 16 Jan 2011 19:16:16 +0800 (CST) MIME-Version: 1.0 Sent to CCL by: Jun Zhang [coolrainbow]-[yahoo.cn] --0-738748691-1295176576=:97253 Content-Type: text/plain; charset=iso-8859-1 Content-Transfer-Encoding: quoted-printable Hello: In my opinion, Koopmans' theorem is based on frozen orbital approximation, = therefore it is uneccessary to relax the nuclei configuration. If you inten= d to get a adiabatic ionization, however, delta SCF is more sutible. Cheers! Jun Zhang =0ANankai University =0Acoolrainbow,+,yahoo.cn =A0Shirin Seifert shirin.seifert|-|gmail.com =A0CCL: koopmans' theorem =A0"Zhang, Jun " Hi, On using the koopmans' theorem to estimate the first and second ionization = energy of a cation, should the geometry of the molecule be that of the cati= on (but neutral)? or the considered geometry is from the optimized neutral = molecule? =0A Thanks for your explanation in advance. Regards, S.S =0A=0A=0A=0A --0-738748691-1295176576=:97253 Content-Type: text/html; charset=iso-8859-1 Content-Transfer-Encoding: quoted-printable
Hello:

In my opinion, Koopmans' theore= m is based on frozen orbital approximation, therefore it is uneccessary to = relax the nuclei configuration. If you intend to get a adiabatic ionization= , however, delta SCF is more sutible.


Cheers!

Jun Zhang=0ANankai University
=0Acoolrainbow,+,yahoo.cn


 Shirin Seifert shirin.seifert|-|gmail.com <owner-chemi= stry,+,ccl.net>
 CCL: koopmans' theorem
 "Zhang, Jun -id#3= zy-" <coolrainbow,+,yahoo.cn>


Hi,
On using the koopmans' theorem to estimate the first and second ioniz= ation energy of a cation, should the geometry of the molecule be that of th= e cation (but neutral)? or the considered geometry is from the optimized ne= utral molecule?
=0A
Thanks for your explanation in advance.

Re= gards,
S.S
=0A

=0A=0A=0A=0A= =0A=0A=0A   --0-738748691-1295176576=:97253-- From owner-chemistry@ccl.net Sun Jan 16 08:23:00 2011 From: "Ehsan Shakerzadeh ehsan_shakerzadeh---yahoo.com" To: CCL Subject: CCL: koopmans' theorem Message-Id: <-43656-110116081614-16983-3d0AhYMvX31ssJgmAuocqw:server.ccl.net> X-Original-From: Ehsan Shakerzadeh Content-Type: multipart/alternative; boundary="0-1339737717-1295183759=:61776" Date: Sun, 16 Jan 2011 05:15:59 -0800 (PST) MIME-Version: 1.0 Sent to CCL by: Ehsan Shakerzadeh [ehsan_shakerzadeh|-|yahoo.com] --0-1339737717-1295183759=:61776 Content-Type: text/plain; charset=iso-8859-1 Content-Transfer-Encoding: quoted-printable Hi=0AIt is necessary to know that what you want to calculate. It means that= for =0Aexample if you want to calculate Hardness or chemical potential usi= ng Koopman =0Atheorem, as the external potential must be constant you must = use vertical IE and =0AEA with single point keyword.(more details J. Phys. = Chem. A 2008, 112, =0A3486-3491)=0A=A0=0AChamran University, =0AAhvaz, Iran= . With Kind Regards,=0AEhsan Shakerzadeh=0AComputational Chemistry Group, = =0AChemistry Departement,=0A=0A=0A=0A=0A________________________________=0A= > From: Shirin Seifert shirin.seifert|-|gmail.com = =0ATo: "Shakerzadeh, Ehsan " =0ASent: = Sun, January 16, 2011 1:29:22 AM=0ASubject: CCL: koopmans' theorem=0A=0AHi,= =0A=0AOn using the koopmans' theorem to estimate the first and second ioniz= ation =0Aenergy of a cation, should the geometry of the molecule be that of= the cation =0A(but neutral)? or the considered geometry is from the optimi= zed neutral =0Amolecule?=0A=0AThanks for your explanation in advance.=0A=0A= Regards,=0AS.S=0A=0A=0A=0A --0-1339737717-1295183759=:61776 Content-Type: text/html; charset=iso-8859-1 Content-Transfer-Encoding: quoted-printable
=0A
=0A

Hi<= ?xml:namespace prefix =3D o ns =3D "urn:schemas-microsoft-com:office:office= " />

=0A

It = is necessary to know that what you want to calculate. It means that for exa= mple if you want to calculate Hardness or chemical potential using Koopman = theorem, as the external potential must be constant you must use vertical I= E and EA with single point keyword.(more details J. Phys. Chem. A 2008, 112= , 3486-3491)

=0A


 With Kin= d Regards,
Ehsan Shakerzadeh
Computational Chemistry Group,
Chemi= stry Departement,

=0A

<= /SPAN>Chamran University,
= Ahvaz, Iran.

=0A

=0A

=0A

=0A
=0A
=0A= From: Shirin Seifert shirin.se= ifert|-|gmail.com <owner-chemistry++ccl.net>
To: "Shakerzadeh, Ehsan " <ehsan_shake= rzadeh++yahoo.com>
Sent: Sun, January 16, 2011 1:29:22 AM
Subject: CCL: koopmans' theorem

Hi,

On usi= ng the koopmans' theorem to estimate the first and second ionization energy= of a cation, should the geometry of the molecule be that of the cation (bu= t neutral)? or the considered geometry is from the optimized neutral molecu= le?

Thanks for your explanation in advance.

Regards,
S.S

=0A=0A --0-1339737717-1295183759=:61776-- From owner-chemistry@ccl.net Sun Jan 16 08:57:00 2011 From: "nathanael weill naweill-*-gmail.com" To: CCL Subject: CCL: in silico biotargets fishing - reverse screening Message-Id: <-43657-110116001317-31352-HEchTXI1ow5fq8yfLINZtQ*|*server.ccl.net> X-Original-From: nathanael weill Content-Type: multipart/alternative; boundary=0016363b84b0a9ffec0499efb86a Date: Sun, 16 Jan 2011 00:13:01 -0500 MIME-Version: 1.0 Sent to CCL by: nathanael weill [naweill^gmail.com] --0016363b84b0a9ffec0499efb86a Content-Type: text/plain; charset=ISO-8859-1 Hi, many approaches exists and can be classified in 3 groups: 1) Protein based. By comparing proteins, known binders from protein A can be predicted as binder of protein B if protein A and protein B are very similar. 2) ligand based. By comparing ligands, if a molecule is similar to a known binder of a protein, then the molecule can be exected to bind this protein. 3) protein ligand based. By comparing complexes of protein ligands, target fishing is possible. In adittion, inverse docking is also possible. I strongly recommend a recent review on that specific topic : http://onlinelibrary.wiley.com/doi/10.1002/minf.200900081/abstract best regards nathanael weill On Fri, Jan 14, 2011 at 6:24 AM, Andrew Voronkov drugdesign[]yandex.ru < owner-chemistry^-^ccl.net> wrote: > > Sent to CCL by: Andrew Voronkov [drugdesign+*+yandex.ru] > Dear CCL users, > I have seen a very interesting presentation from Intelligand on biotargets > in silico deconvolution for the known compounds. This is pharmacophore-based > screening approach for some sets of biotargets. What are other methods, > software and approaches available for in silico biotarget identification for > compounds without know targets-mechanisms of action? The best of course > would be to find some tools which is possible to use locally? > > > Best regards, > Andrew> > > -- Nathanael WEILL, PhD McGill University Department of Chemistry Otto Maass Building 801 Sherbrooke St. West, lab 206A Montreal, QC, Canada H3A 2K6 Phone: 514-398-5501 Fax: 514-398-3797 nathanael.weill^-^mail.mcgill.ca --0016363b84b0a9ffec0499efb86a Content-Type: text/html; charset=ISO-8859-1 Content-Transfer-Encoding: quoted-printable
Hi,
many approaches exists and can be classified in 3 groups:
1) Protein based. By comparing proteins, known binders from protein A= can be predicted as binder of protein B if protein A and protein B are ver= y similar.=A0
2) ligand based. By comparing ligands, if a molecule is similar to a k= nown binder of a protein, then the molecule can be exected to bind this pro= tein.
3) protein ligand based. By comparing complexes of protein = ligands, target fishing is possible.=A0In adittion, inverse docking is also= possible.

I strongly recommend a recent review on that specific t= opic :=A0http://onlinelibrary.wiley.com/doi/10.1002/m= inf.200900081/abstract

best regards
nathanael weill

On Fri, Jan 14, 2011 at 6:24 AM, Andrew Voronkov drugde= sign[]yandex.ru <= owner-chemistry^-^ccl.net> wrote:

Sent to CCL by: Andrew Voronkov [drugdesign+*+yandex.ru]
Dear CCL users,
I have seen a very interesting presentation from Intelligand on biotargets = in silico deconvolution for the known compounds. This is pharmacophore-base= d screening approach for some sets of biotargets. What are other methods, s= oftware and approaches available for in silico biotarget identification for= compounds without know targets-mechanisms of action? The best of course wo= uld be to find some tools which is possible to use locally?


Best regards,
Andrew



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--
=A0 =A0 =A0 =A0 =A0 =A0= =A0 =A0
Nathanael WEILL, PhD
McGill University
Department of Che= mistry
Otto Maass Building
801 Sherbrooke St. West, lab 206A
Montr= eal, QC, Canada
H3A 2K6

Phone: 514-398-5501
Fax: 514-398-3797
nathanael.weill^-^mail.mc= gill.ca

--0016363b84b0a9ffec0499efb86a-- From owner-chemistry@ccl.net Sun Jan 16 13:51:00 2011 From: "Nancy nancy5villa**gmail.com" To: CCL Subject: CCL: Pioglitazone Tautomers Message-Id: <-43658-110116132929-1728-gZpXEmPpgqrQNFY3DBy5tQ/./server.ccl.net> X-Original-From: Nancy Content-Type: multipart/alternative; boundary=00248c11da372a17cd0499fad862 Date: Sun, 16 Jan 2011 13:29:14 -0500 MIME-Version: 1.0 Sent to CCL by: Nancy [nancy5villa[]gmail.com] --00248c11da372a17cd0499fad862 Content-Type: text/plain; charset=ISO-8859-1 Content-Transfer-Encoding: quoted-printable Using quantum chemical calculations, you found that the diketone form is dominant; does this mean that the enol form predicted by MarvinSketch v3.5.= 4 in the published article is wrong? "Structure-based design of a thiazolidinedione which targets the mitochondrial protein mitoNEET" Bioorg Med Chem Lett. 2010 Feb 1;20(3):819-23 Thanks, Nancy On Thu, Jan 13, 2011 at 10:31 PM, Andreas Klamt klamt(a)cosmologic.de < owner-chemistry,+,ccl.net> wrote: > Sent to CCL by: Andreas Klamt [klamt,cosmologic.de] > Hi Nancy, > > as I wrote in the previous message, we find by quantum chemical > calculations within the COSMO-RS solvation that the diketone form is more > stable by abot 12 kcal/mol, that means it absolutely dominates! > > Andreas > > Am 13.01.2011 22:25, schrieb Nancy nancy5villa~!~gmail.com: > > Hi All, > > I happened to find a published article where molecular docking simulation= s > of TZDs against a novel protein is detailed: > > "Structure-based design of a thiazolidinedione which targets the > mitochondrial protein mitoNEET" Bioorg Med Chem Lett. 2010 Feb > 1;20(3):819-23 > > In this paper, the authors, using MarvinSketch v3.5.4, determined that th= e > TZDs would exist predominantly in the enol form at pH 7.4, as opposed to = the > diketone form (see attached figure). It appears that the article's tauto= mer > prediction was based only on the pH prior to docking, and had nothing to = do > with ligand-protein interactions. > > Does anyone know if the diketone or enol, or perhaps a different tautomer= , > would be predominant at pH 7.4? > > Thanks in advance. > Nancy > > > > On Wed, Jan 12, 2011 at 9:53 AM, Andreas Klamt klamt-*-cosmologic.de < > owner-chemistry(_)ccl.net > wrote: > >> >> Sent to CCL by: Andreas Klamt [klamt[*]cosmologic.de] >> Hi All, >> >> let me put my 5 cents into the game: >> We have done quantum calculations for the heterocyclic ring, with just a >> methyl group, since electronically the remainder of the compound should = have >> almost no influence on the heterocycle. >> DFT/COSMO-RS calculations prove the neutral species >> SMILES:CC1C(=3DO)[NH]C(=3DO)S1 of the Pioglitazone heterocycle to be fav= ored >> by 11.3 kcal/mol compared to all other neutral species of the heterocycl= e, >> which means that there is no other relvant neutral form. >> >> We find with COSMOtherm that the pka of the heterocycle is 6.55, i.e. at >> pH=3D7 it should be deprotonated with about 25%. >> Since the pka of the conj. acid of the pyridine ring according to >> COSMOtherm (we calculated diethylpyridine) is ~5.6 there should be ~10% = in >> the zwitterionic form. >> >> It will be hard to decide this finally, unless someone measures it, but = we >> are quite confident to be qualitatively right here, because the energy >> differences for the tautomers should not have more than 5 kcal/mol erro,= as >> we learned in in the SAMPL2 tautomer contest: >> see Andreas Klamt and Michael Diedenhofen, Some conclusions regarding th= e >> predictions of tautomeric equilibria in solution based on the SAMPL2 >> challenge, http://www.springerlink.com/content/l577667th758n6h1/ >> >> Andreas >> >> >> >> >> >> >>> >>> Hi All, >>> >>> Using MarvinSketch v5.3.3 (ChemAxon software), the predicted pKa value >>> of the acidic hydrogen on the thiazolidinedione ring of pioglitazone is >>> 4.57 (see attached "Figure_1.gif"). Therefore, the predominant species >>> at pH 7.0 predicted by MarvinSketch is the one depicted in >>> "Figure_2.gif". The different tautomeric forms predicted by MarvinSketc= h >>> are shown in "Figure_3.gif". >>> >>> Can anyone explain where these predictions come from, and if they are >>> correct? >>> >>> Thanks, >>> Nancy >>> >>> >>> On Mon, Jan 10, 2011 at 4:16 AM, Gabriele Cruciani >>> gabri(0)chemiome.chm.unipg.it >>> >>> > wrote: >>> >>> >>> Sent to CCL by: Gabriele Cruciani [gabri##chemiome.chm.unipg.it >>> ] >>> >>> Nancy, >>> the first form you reported is the most stable in water at pH 7.0. >>> However, the fact that one form is more stable than another in water >>> does not help you to understand which form will be more 'relevant' >>> for docking. In protein the tautomeric equilibria may produce and >>> stabilize different forms according to the complementary site. There >>> are examples of tautomeric form in protein not stable in water, >>> where the energy difference is more than 5 Kcal/mol. >>> >>> MoKa software (www.moldiscovery.com ) >>> >>> is fast and accurate to produce tautomer stable in water, but it can >>> produce also all the (plausible) tautomeric forms. >>> >>> Then, a possibility is to dock them into your protein, to see if >>> docking methods may differentiate their binding. >>> >>> Gabriele Cruciani >>> >>> >>> >>> >>> Hi All, >>> >>> I am performing molecular docking and molecular dynamics >>> simulations of the >>> thiazolidinedione pioglitazone binding to the PPAR-gamma >>> receptor protein >>> (PDB ID: 1ZGY). The thiazolidinedione ring can exist in numerous >>> different >>> tautomeric states; I have attached a figure depicting several of >>> them. >>> Which tautomer would be dominant at the physiological pH of ~7.0= ? >>> >>> Also, are there any software programs that can predict which >>> tautomer would >>> be correct? >>> >>> Thanks in advance, >>> Nancy> >>> >>> >>> E-mail to subscribers: CHEMISTRY[a]ccl.net >>> or use:> >>> E-mail to administrators: CHEMISTRY-REQUEST[a]ccl.net >>> or useConferences: >>> >>> http://server.ccl.net/chemistry/announcements/conferences/> >>> >>> >>> >>> >> -- >> Dr. Jens Reinisch >> Chemist / Customer Support >> COSMOlogic GmbH & Co. KG >> Burscheider Strasse 515 >> D-51381 Leverkusen, Germany >> >> phone +49-2171-363664 >> mobile +49-163-7337310 >> fax +49-2171-731689 >> e-mail reinisch[*]cosmologic.de >> web www.cosmologic.de >> >> HRA 20653 Amtsgericht Koeln, GF: Dr. Andreas Klamt >> Komplementaer: COSMOlogic Verwaltungs GmbH >> HRB 49501 Amtsgericht Koeln, GF: Dr. Andreas Klamt >> >> >> >> >> >> >> E-mail to subscribers: CHEMISTRY(_)ccl.net or >> use:>> >> E-mail to administrators: CHEMISTRY-REQUEST(_)ccl.netor useConferences: >> http://server.ccl.net/chemistry/announcements/conferences/>> >> >> > > > -- > PD. Dr. Andreas Klamt > CEO / Gesch=E4ftsf=FChrer > COSMOlogic GmbH & Co. KG > Burscheider Strasse 515 > D-51381 Leverkusen, Germany > > phone +49-2171-731681 > fax +49-2171-731689 > e-mail klamt(_)cosmologic.de > > web www.cosmologic.de > > HRA 20653 Amtsgericht Koeln, GF: Dr. Andreas Klamt > Komplementaer: COSMOlogic Verwaltungs GmbH > HRB 49501 Amtsgericht Koeln, GF: Dr. Andreas Klamt > > -=3D This is automatically added to each message by the mailing script = =3D- To > recover the email address of the author of the message, please change the > strange characters on the top line to the ,+, sign. You can also look up th= e > X-Original-From: line in the mail header. E-mail to subscribers: > CHEMISTRY,+,ccl.net or use:= E-mail to administrators: > CHEMISTRY-REQUEST,+,ccl.net or useBefore posting, check wait > time at: http://www.ccl.netConferences: > http://server.ccl.net/chemistry/announcements/conferences/ Search > Messages: http://www.ccl.net/chemistry/searchccl/index.shtml If your mail > bounces from CCL with 5.7.1 error, check:= RTFI: > http://www.ccl.net/chemistry/aboutccl/instructions/ --00248c11da372a17cd0499fad862 Content-Type: text/html; charset=ISO-8859-1 Content-Transfer-Encoding: quoted-printable Using quantum chemical calculations, you found that the diketone form is do= minant; does this mean that the enol form predicted by MarvinSketch v3.5.4 = in the published article is wrong?

"Structure-based design of a= thiazolidinedione which targets the mitochondrial protein mitoNEET" B= ioorg Med Chem Lett. 2010 Feb 1;20(3):819-23

Thanks,
Nancy


On Thu, Jan 13, = 2011 at 10:31 PM, Andreas Klamt klamt(a)co= smologic.de <owner-chemistry,+,ccl.net> wrote:
Sent to CCL by: Andreas Klamt [klamt,cosmologic.de] =20 =20 =20
Hi Nancy,

as I wrote in the previous message, we find by quantum chemical calculations within the COSMO-RS solvation that the diketone form is more stable by abot 12 kcal/mol, that means it absolutely dominates!
Andreas

Am 13.01.2011 22:25, schrieb Nancy nancy5villa~!~gmail.com:
Hi All,

I happened to find a published article where molecular docking simulations of TZDs against a novel protein is detailed:

"Structure-based design of a thiazolidinedione which targets the mitochondrial protein mitoNEET" Bioorg Med Chem Lett. 2010 Feb 1;20(3):819-23

In this paper, the authors, using MarvinSketch v3.5.4, determined that the TZDs would exist predominantly in the enol form at pH 7.4, as opposed to the diketone form (see attached figure).=A0 It appears that the article's tautomer prediction was based only on the pH prior to docking, and had nothing to do with ligand-protein interactions.

Does anyone know if the diketone or enol, or perhaps a different tautomer, would be predominant at pH 7.4?

Thanks in advance.
Nancy



On Wed, Jan 12, 2011 at 9:53 AM, Andreas Klamt klamt-*-co= smologic.de <owner-chemistry(_)ccl.net> wrote:

Sent to CCL by: Andreas Klamt [klamt[*]cosmologic.de]
Hi All,

let me put my 5 cents into the game:
We have done quantum calculations for the heterocyclic ring, with just a methyl group, since electronically the remainder of the compound should have almost no influence on the heterocycle.
DFT/COSMO-RS calculations prove the neutral species
SMILES:CC1C(=3DO)[NH]C(=3DO)S1 of the Pioglitazone heterocycle to be favored by 11.3 kcal/mol compared to all other neutral species of the heterocycle, which means that there is no other relvant neutral form.

We find with COSMOtherm that the pka of the heterocycle is 6.55, i.e. at pH=3D7 it should be deprotonated with about 25%. Since the pka of the conj. acid of the pyridine ring according to COSMOtherm (we calculated diethylpyridine) is ~5.6 there should be ~10% in the zwitterionic form.

It will be hard to decide this finally, unless someone measures it, but we are quite confident to be qualitatively right here, because the energy differences for the tautomers should not have more than 5 kcal/mol erro, as we learned in in the SAMPL2 tautomer contest:
see Andreas Klamt and Michael Diedenhofen, Some conclusions regarding the predictions of tautomeric equilibria in solution based on the SAMPL2 challenge, http://www.springerlink.c= om/content/l577667th758n6h1/

Andreas







Hi All,

Using MarvinSketch v5.3.3 (ChemAxon software), the predicted pKa value
of the acidic hydrogen on the thiazolidinedione ring of pioglitazone is
4.57 (see attached "Figure_1.gif"). Therefore, the predominant species
at pH 7.0 predicted by MarvinSketch is the one depicted in "Figure_2.gif". The different tautomeric forms pred= icted by MarvinSketch
are shown in "Figure_3.gif".

Can anyone explain where these predictions come from, and if they are
correct?

Thanks,
Nancy


On Mon, Jan 10, 2011 at 4:16 AM, Gabriele Cruciani
gabri(0)chemiome.chm.unipg.it <= http://chemiome.chm.unipg.it>

<owner-chemistry[a]ccl.net <mailto:owner-chemistry[a]ccl.n= et>> wrote:


=A0 =A0Sent to CCL by: Gabriele Cruciani [gabri##chemiome.chm.unipg.it
=A0 =A0<http://chemiome.chm.unipg.it>]

=A0 =A0Nancy,
=A0 =A0the first form you reported is the most stable in wate= r at pH 7.0.
=A0 =A0However, the fact that one form is more stable than another in water
=A0 =A0does not help you to understand which form will be mor= e 'relevant'
=A0 =A0for docking. In protein the tautomeric equilibria may produce and
=A0 =A0stabilize different forms according to the complementary site. There
=A0 =A0are examples of tautomeric form in protein not stable in water,
=A0 =A0where the energy difference is more than 5 Kcal/mol.
=A0 =A0MoKa software (www.moldiscovery.com <h= ttp://www.moldiscovery.com>)

=A0 =A0is fast and accurate to produce tautomer stable in water, but it can
=A0 =A0produce also all the (plausible) tautomeric forms.

=A0 =A0Then, a possibility is to dock them into your protein, to see if
=A0 =A0docking methods may differentiate their binding.

=A0 =A0Gabriele Cruciani




=A0 =A0 =A0 =A0Hi All,

=A0 =A0 =A0 =A0I am performing molecular docking and molecula= r dynamics
=A0 =A0 =A0 =A0simulations of the
=A0 =A0 =A0 =A0thiazolidinedione pioglitazone binding to the PPAR-gamma
=A0 =A0 =A0 =A0receptor protein
=A0 =A0 =A0 =A0(PDB ID: 1ZGY). The thiazolidinedione ring can exist in numerous
=A0 =A0 =A0 =A0different
=A0 =A0 =A0 =A0tautomeric states; I have attached a figure depicting several of
=A0 =A0 =A0 =A0them.
=A0 =A0 =A0 =A0Which tautomer would be dominant at the physiological pH of ~7.0?

=A0 =A0 =A0 =A0Also, are there any software programs that can predict which
=A0 =A0 =A0 =A0tautomer would
=A0 =A0 =A0 =A0be correct?

=A0 =A0 =A0 =A0Thanks in advance,
=A0 =A0 =A0 =A0Nancy>


=A0 =A0E-mail to subscribers: CHEMISTRY[a]ccl.net
=A0 =A0<mailto:CHEMISTRY[a]ccl.net&= gt; or use:>
=A0 =A0E-mail to administrators: CHEMISTRY-REQUEST[a]ccl.net
=A0 =A0<mailto:CHEMISTRY-REQUEST[a]ccl.net> or useConferences:

--
Dr. Jens Reinisch
Chemist / Customer Support
COSMOlogic GmbH & Co. KG
Burscheider Strasse 515
D-51381 Leverkusen, Germany

phone =A0 +49-2171-363664
mobile =A0+49-163-7337310
fax =A0 =A0 +49-2171-731689
e-mail =A0reinisch[*]cosmologic.de
web =A0 =A0 www.cosmologic.de

HRA 20653 Amtsgericht Koeln, GF: Dr. Andreas Klamt
Komplementaer: COSMOlogic Verwaltungs GmbH
HRB 49501 Amtsgericht Koeln, GF: Dr. Andreas Klamt 



--=20
PD. Dr. Andreas Klamt
CEO / Gesch=E4ftsf=FChrer
COSMOlogic GmbH & Co. KG
Burscheider Strasse 515
D-51381 Leverkusen, Germany

phone  	+49-2171-731681
fax    	+49-2171-731689
e-mail 	klam=
t(_)cosmologic.de

web    	www.cosmolog=
ic.de

HRA 20653 Amtsgericht Koeln, GF: Dr. Andreas Klamt
Komplementaer: COSMOlogic Verwaltungs GmbH
HRB 49501 Amtsgericht Koeln, GF: Dr. Andreas Klamt
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