From owner-chemistry@ccl.net Tue Jan 11 16:45:00 2011 From: "Nancy nancy5villa%x%gmail.com" To: CCL Subject: CCL:G: Pioglitazone Tautomers Message-Id: <-43604-110111155619-6891-GNor3OvCB0AJzpnE4p0KDw[]server.ccl.net> X-Original-From: Nancy Content-Type: multipart/mixed; boundary=0015174734b60a79410499985054 Date: Tue, 11 Jan 2011 15:56:03 -0500 MIME-Version: 1.0 Sent to CCL by: Nancy [nancy5villa%gmail.com] --0015174734b60a79410499985054 Content-Type: multipart/alternative; boundary=0015174734b60a793b0499985052 --0015174734b60a793b0499985052 Content-Type: text/plain; charset=ISO-8859-1 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 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 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/> > > --0015174734b60a793b0499985052 Content-Type: text/html; charset=ISO-8859-1 Content-Transfer-Encoding: quoted-printable Hi All,

Using MarvinSketch v5.3.3 (ChemAxon software), the predicted= pKa value of the acidic hydrogen on the thiazolidinedione ring of pioglita= zone is 4.57 (see attached "Figure_1.gif").=A0 Therefore, the pre= dominant species at pH 7.0 predicted by MarvinSketch is the one depicted in= "Figure_2.gif".=A0 The different tautomeric forms predicted by M= arvinSketch are shown in "Figure_3.gif".

Can anyone explain where these predictions come from, and if they are c= orrect?

Thanks,
Nancy


On Mo= n, 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




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