From owner-chemistry@ccl.net Fri Nov 30 08:19:01 2012 From: "Mariyam Haque mariyam.haque^-^iccs.edu" To: CCL Subject: CCL: Rmsd of redocked poses Message-Id: <-47946-121130030545-23714-U8W8FfV2KWya32LRN/aZOg^_^server.ccl.net> X-Original-From: "Mariyam Haque" Date: Fri, 30 Nov 2012 03:05:43 -0500 Sent to CCL by: "Mariyam Haque" [mariyam.haque(0)iccs.edu] Hi, I have performed redocking studies on 19 pdbs of the same protein to validate the docking protocol before virtual screening. In most cases I have values of rmsds of best ranked poses < 1 while in 5 of the pdbs I have values above three. Upon visual inspection and rmsd calculation of poses other than the best ranked ones for these five, I find that often the 'other' poses have rmsds below 2 (which is acceptable). I would like to know how could I justify these results. Thanks Mariyam Haque mariyam.s.haque/./gmail.com, mariyam.haque/./iccs.edu Computational Drug Design Unit, Dr. Panjwani Center for Molecular Medicine and Drug Research, University of Karachi, Pakistan From owner-chemistry@ccl.net Fri Nov 30 15:22:00 2012 From: "mahnaz gh mahnaz271163,,yahoo.com" To: CCL Subject: CCL: how to use two basis set in one input Message-Id: <-47947-121130133350-26311-B3Uk0F94odfmehEVJdXY9g[*]server.ccl.net> X-Original-From: "mahnaz gh" Date: Fri, 30 Nov 2012 13:33:49 -0500 Sent to CCL by: "mahnaz gh" [mahnaz271163++yahoo.com] I have an almost large molecule,aligand and and a transition metal. How can I optimize the ligand atoms with B3LYP/6-311+G level of theory and the metal with B3LYP/DZVP? I want to know how should I explain for gaussview this command? Best regards, mahnaz gh From owner-chemistry@ccl.net Fri Nov 30 16:58:01 2012 From: "Vladimir Chupakhin chupvl%%gmail.com" To: CCL Subject: CCL: Rmsd of redocked poses Message-Id: <-47948-121130144842-17591-JtNA8j9XeB1A/V7pffb/hA!A!server.ccl.net> X-Original-From: Vladimir Chupakhin Content-Type: multipart/alternative; boundary=0015174c33c471835b04cfbbaf16 Date: Fri, 30 Nov 2012 11:47:55 -0800 MIME-Version: 1.0 Sent to CCL by: Vladimir Chupakhin [chupvl^-^gmail.com] --0015174c33c471835b04cfbbaf16 Content-Type: text/plain; charset=UTF-8 Hello, It's just don't work for that poses and the reasons can be different. But keep in mind that RMSD is not the best measure of docking quality, because of several factors. For example if you have long substituent that do not bind the same way as in x-ray and do not form any important interactions - just treat it as correct. Also if you have removed water from the binding site and they do participate in interactions with ligands - the original position can be moved. The other point - sometimes ligands have symmetry plane of pharmacophoric patterns - thus rotation of the ligand 180 degrees will produce the same interactions but of course RMSD will be hugely different. For virtual screening I consider first make an test run for better validation of the scoring function by using DUDe service (dude.docking.org) to produce the decoys (inactive) compounds and dock them to protein and producing ROC curve. Vladimir Chupakhin, San Diego, CA, USA On Fri, Nov 30, 2012 at 12:05 AM, Mariyam Haque mariyam.haque^-^iccs.edu < owner-chemistry*ccl.net> wrote: > > Sent to CCL by: "Mariyam Haque" [mariyam.haque(0)iccs.edu] > Hi, > > I have performed redocking studies on 19 pdbs of the same protein to > validate the docking protocol before virtual screening. In most cases I > have values of rmsds of best ranked poses < 1 while in 5 of the pdbs I have > values above three. Upon visual inspection and rmsd calculation of poses > other than the best ranked ones for these five, I find that often the > 'other' poses have rmsds below 2 (which is acceptable). > > I would like to know how could I justify these results. > > Thanks > > Mariyam Haque > mariyam.s.haque|gmail.com, mariyam.haque|iccs.edu > Computational Drug Design Unit, Dr. Panjwani Center for Molecular Medicine > and Drug Research, University of Karachi, Pakistan> > > --0015174c33c471835b04cfbbaf16 Content-Type: text/html; charset=UTF-8 Content-Transfer-Encoding: quoted-printable Hello,

It's just don't work for that poses and t= he reasons can be different.

But keep in mind that= RMSD is not the best measure of docking quality, because of several factor= s.
For example if you have long substituent that do not bind the same way= as in x-ray and do not form any important interactions - just treat it as = correct. Also if you have removed water from the binding site and they do p= articipate in interactions with ligands - the original position can be move= d. The other point - sometimes ligands have=C2=A0symmetry plane=C2=A0of=C2= =A0pharmacophoric patterns - thus rotation of the ligand 180 degrees will p= roduce the same interactions but of course RMSD will be hugely different.

For virtual screening I consider first make an test run= for better validation of the scoring function by using DUDe service (dude.docking.org) to produce the decoys = (inactive) compounds and dock them to protein and producing ROC curve.

Vladimir Chupakhin,
=
San Diego, CA, USA




On Fri, Nov 30, 2012 at 12:05 AM, Mariya= m Haque mariyam.haque^-^iccs.edu <o= wner-chemistry*ccl.net> wrote:

Sent to CCL by: "Mariyam =C2=A0Haque" [mariyam.haque(0)iccs.edu]
Hi,

I have performed redocking studies on 19 pdbs of the same protein to valida= te the docking protocol before virtual screening. In most cases I have valu= es of rmsds of best ranked poses < 1 while in 5 of the pdbs I have value= s above three. Upon visual inspection and rmsd calculation of poses other t= han the best ranked ones for these five, I find that often the 'other&#= 39; poses have rmsds below 2 (which is acceptable).

I would like to know how could I justify these results.

Thanks

Mariyam Haque
mariyam.s.haque|gmail.com, mariyam.haque|iccs.edu=
Computational Drug Design Unit, Dr. Panjwani Center for Molecular Medicine = and Drug Research, University of Karachi, Pakistan



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--0015174c33c471835b04cfbbaf16-- From owner-chemistry@ccl.net Fri Nov 30 17:34:00 2012 From: "Rupashree Ray shyama.tum%a%gmail.com" To: CCL Subject: CCL: how to use two basis set in one input Message-Id: <-47949-121130173309-22590-Lge8lSrXj4NA/Gnw9Ft6Vw[]server.ccl.net> X-Original-From: "Rupashree Ray" Date: Fri, 30 Nov 2012 17:33:08 -0500 Sent to CCL by: "Rupashree Ray" [shyama.tum|-|gmail.com] Hi Mahnaz, In order to define 2 basis sets, you can use the section Add Input in gaussview. This will come after the coordinate section of your input. The lines should look like this... C O H 0 3-21G **** Zn 0 DZVP **** B3LYP you can mention in method section. Also specify basis set as gen. I hope this helps you. Best Ray From owner-chemistry@ccl.net Fri Nov 30 21:08:01 2012 From: "Regina Politi reginap%a%unc.edu" To: CCL Subject: CCL: Rmsd of redocked poses Message-Id: <-47950-121130172410-17792-Gito25TBoob+RABdUEufRQ#,#server.ccl.net> X-Original-From: "Regina Politi" Date: Fri, 30 Nov 2012 17:24:09 -0500 Sent to CCL by: "Regina Politi" [reginap:+:unc.edu] Dear Miriyam, In the process of docking ligand finds its position into the proteins active site after a certain number of moves in its conformational space. The moves incorporate rigid body transformations such as translations and rotations, as well as internal changes to the ligands structure including torsion angle rotations. Each of these moves in the conformation space of the ligand induces a total energetic cost of the system, and hence after every move the total energy of the system is calculated. Force field energy evaluation are most often used to select energetically reasonable conformations. In most of the cases the native conformation (native pose) has the lowest energy but it is possibly for a pose to deviate from native conformation and yet to have the lowest force field energy. Especially it should be considered that not all the possible energy terms are taken into account when the force field energy is calculated. For example such term as solvetion entropy is not taken into account. Hope it helps, Regina > "Mariyam Haque mariyam.haque^-^iccs.edu" wrote: > > Sent to CCL by: "Mariyam Haque" [mariyam.haque(0)iccs.edu] > Hi, > > I have performed redocking studies on 19 pdbs of the same protein to validate the docking protocol before virtual screening. In most cases I have values of rmsds of best ranked poses < 1 while in 5 of the pdbs I have values above three. Upon visual inspection and rmsd calculation of poses other than the best ranked ones for these five, I find that often the 'other' poses have rmsds below 2 (which is acceptable). > > I would like to know how could I justify these results. > > Thanks > > Mariyam Haque > mariyam.s.haque/./gmail.com, mariyam.haque/./iccs.edu > Computational Drug Design Unit, Dr. Panjwani Center for Molecular Medicine and Drug Research, University of Karachi, Pakistan > >