From owner-chemistry@ccl.net Mon Jan 10 16:20:00 2011 From: "Nancy nancy5villa]-[gmail.com" To: CCL Subject: CCL: Pioglitazone Tautomers Message-Id: <-43594-110110145148-15882-mK/nlsIcw0zsd3wF3EGYFA^-^server.ccl.net> X-Original-From: Nancy Content-Type: multipart/alternative; boundary=20cf3054a61978e1d504998349b5 Date: Mon, 10 Jan 2011 14:50:59 -0500 MIME-Version: 1.0 Sent to CCL by: Nancy [nancy5villa{}gmail.com] --20cf3054a61978e1d504998349b5 Content-Type: text/plain; charset=ISO-8859-1 How do you know that the first tautomer (diketone) is the most stable at pH 7.0? 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, >> Nancyhttp://www.ccl.net/chemistry/sub_unsub.shtmlConferences: > http://server.ccl.net/chemistry/announcements/conferences/> > > --20cf3054a61978e1d504998349b5 Content-Type: text/html; charset=ISO-8859-1 Content-Transfer-Encoding: quoted-printable How do you know that the first tautomer (diketone) is the most stable at pH= 7.0?

Thanks,
Nancy



On = Mon, Jan 10, 2011 at 4:16 AM, Gabriele Cruciani gabri(0)chemiome.chm.unipg.it <owner-chemistry[]ccl.net> 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 n= ot help you to understand which form will be more 'relevant' for do= cking. In protein the tautomeric equilibria may produce and stabilize diffe= rent forms according to the complementary site. There are examples of tauto= meric form in protein not stable in water, where the energy difference is m= ore than 5 Kcal/mol.

MoKa software (ww= w.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 me= thods 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). =A0The thiazolidinedione ring can exist in numerous differe= nt
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




-=3D This is automatically added to each message by the mailing script =3D-=
E-mail to subscribers: CHEMISTRY[]ccl.net or use:
=A0 =A0 http://www.ccl.net/cgi-bin/ccl/send_ccl_message

E-mail to administrators: CHEMISTRY-REQUEST[]ccl.net or use
=A0 =A0 http://www.ccl.net/cgi-bin/ccl/send_ccl_message
http://www.ccl.net/chemistry/sub_unsub.sh= tml

Before posting, check wait time at: http://www.ccl.net

Job: http://www.ccl.n= et/jobs Conferences: http://server.ccl.net/chemistry/anno= uncements/conferences/

Search Messages: http://www.ccl.net/chemistry/searchccl/index.shtml
=A0 =A0 http= ://www.ccl.net/spammers.txt

RTFI: http://www.ccl.net/chemistry/aboutccl/instructions/



--20cf3054a61978e1d504998349b5--