From chemistry-request@server.ccl.net Wed Feb 20 08:59:41 2002 Received: from gate.boehringer-ingelheim.de ([148.188.1.36]) by server.ccl.net (8.11.6/8.11.0) with SMTP id g1KDxe524294 for ; Wed, 20 Feb 2002 08:59:41 -0500 Received: from bibex01.bc.de.bic by gate.boehringer-ingelheim.de via smtpd (for server.ccl.net [192.153.40.39]) with SMTP; 20 Feb 2002 13:57:24 UT Received: by bibex01.eu.boehringer.com with Internet Mail Service (5.5.2653.19) id <1NL3F327>; Wed, 20 Feb 2002 14:59:13 +0100 Message-ID: From: Christian.Pilger@bc.boehringer-ingelheim.com To: chemistry@ccl.net Subject: aqueous solubilities of organic compounds Date: Wed, 20 Feb 2002 14:59:13 +0100 MIME-Version: 1.0 X-Mailer: Internet Mail Service (5.5.2653.19) Content-Type: text/plain; charset="iso-8859-1" Content-Transfer-Encoding: 8bit X-MIME-Autoconverted: from quoted-printable to 8bit by server.ccl.net id g1KDxf524295 Dear collegues, as I promised, I provide you with a summary of replies, that I received upon my request about methods for the prediction of aqueous solubilities. I would like to thank everyone, who responded ! Best regards, Christian ________________________________________________________________ Dr. Christian Pilger Dept. Chemical Research / Structural Research K91-00-10 Boehringer Ingelheim Pharma KG D-88397 Biberach/Germany Phone: 07351-545749 Fax: 07351-5497924 mailto: christian.pilger@bc.boehringer-ingelheim.com --------------------------- Carlos Faerman [CFaerman@etrx.com] Dear Dr. Pilger, This is a very important issue in the pharma/biotech world ! I have two remarks to make: 1) The experimental values for solubilities are available, among other sources, in the Beilstein database, currently available online. 2)Without endorsing any specific software company, Gastro Plus by Simulations Plus, Lancaster California seems to have a reasonable success in predicting solubility. I would be very interested in finding out what your experience or someone else's is in this field. --------------------------- David Gallagher [dgallagher@cachesoftware.com] There is a zipped file which includes a water solubility QSPR along with the calibration set of 156 environmentally significant organic molecules and water solubility data available at: http://www.cachesoftware.com/downloads/LogW.zip The QSPR uses descriptors calculated by MOPAC-COSMO. The r^2 correlation is 0.95. It is located on: http://www.cachesoftware.com/cache/applications.shtml If you do not already have the CAChe software to open the files, you can download a free evaluation copy from the same site. David Gallagher, Fujitsu --------------------------- David van der Spoel [spoel@xray.bmc.uu.se] Check out: @Article{Wang2001b, author = {J. M. Wang and W. Wang and S. H. Huo and M. Lee and P. A. Kollman}, title = {Solvation model based on weighted solvent accessible surface area}, journal = {J. Phys. Chem. B}, year = 2001, volume = 105, pages = {5055-5067} } A very simple area based method. However, I haven't been able to get meaningful numbers out of it.. --------------------------- Dearden John [J.C.Dearden@livjm.ac.uk] We have recently tested the ability of a number of software packages to predict aqueous solubility, and I attach a few PowerPoint slides with some preliminary results. We took our 113 compounds from a data-set of over 600 solubilities published by Abraham and Le (J. Pharm. Sci. 88 (1999) 868-880, by taking roughly every sixth compound. I've included a similar comparison of log P predictions, from which you can see that the ability to predict log S is nothing like so good as the ability to predict log P. --------------------------- Erik Johansson [erik.johansson@umetrics.com] Arne Brändström (retired from AZ Mölndal) has worked a lot on his own method for aqueous solubility. I saw a early manuscript a couple of years ago but I am not sure if this is published. --------------------------- George Vacek [vacek@schrodinger.com] QikProp predicts a variety of pharmaceutical properties, including solubility, that are important in determining ADME characteristics for drug candidates. The complete set of properties predicted by QikProp, methods, data and literature references are available at http://www.schrodinger.com For the specific case of solubility, the data set and descriptors are detailed in the article W. L. Jorgensen and E. M. Duffy, Bioorg. Med. Chem. Lett., 10 (2000) 1155-8. --------------------------- Igor Tetko [itetko@yahoo.com] You can use our ALOGPS software that predict both aqueous solubility and lipophilicity of chemicals. The description of this software can be found at: Tetko, I.V.; Tanchuk, V. Yu.; Kasheva, T. N.; Villa, A. E. P. Estimation of Aqueous Solubility of Chemical Compounds Using E-state Indices, J. Chem. Inf. Comput. Sci., 2001, 41, 1488-1493. Tetko, I.V.; Tanchuk, V. Yu.; Villa, A. E. P. Prediction of n-Octanol/Water Partition Coefficients from PHYSPROP Database Using Artificial Neural Networks and E-state Indice, J. Chem. Inf. Comput. Sci., 2001, 41, 1407-1421. Tetko, I.V.; Tanchuk, V.Yu.; Kasheva, T.N.; Villa, A.E.P. Internet Software for Calculation of Lipophilicity and Aqueous Solubility of Chemical Compounds, J. Chem. Inf. Comput. Sci., 2001, 41, 246-252. We have new version 2.1 of this program that is available for testing as a standalone program. You can also use free on-line version ALOGPS 2.0 available at WWW http://www.lnh.unil.ch/~itetko/logp. A nice feature of the standalone version is a possibility to create a user's LIBRARY of compounds. This can improve prediction of this software for similar compounds in 2-3 times (article in preparation). The ALOGPS 2.1 will be available at the WWW soon. The description of the algorithm used in the LIBRARY mode, Associative Neural Network, will be published in JCICS soon (I am waiting for the galley-proof of the article). You can download the set of compounds used in the aqueous solubility study at http://www.lnh.unil.ch/~itetko/logp/logs.html --------------------------- John McKelvey [jmmckel@attglobal.net] I think that one of the best beople to talk to about this might be Andreas Klampt there in Germany...Andreas.Klamt@CosmoLogic.de --------------------------- Hugo Kubinyi [kubinyi@t-online.de] Dear Dr. Pilger, there is a simple solution for liquids - just take the inverse lipophilicity as a good estimate. The problem is much more difficult for solids. Most probably you know about the correlation of solubility with log P and mp. - however there is no method to predict the mp., the crystal lattice, the intermolecular forces in the crystal and, therefore, no possibility to predict the solvation enthalpy and entropy - which influences lipophilicity. If somebody (especially vendors) tells you something else, you should be a little suspicious. For a database that is not too expensive see: http://esc.syrres.com/interkow/PhysProp.htm --------------------------- Robert L. Lipnick [Lipnick.Robert@epamail.epa.gov] Check papers on water solubility estimation from chemical structure and log P and MP by Samuel Yalkowsky, Univ. of Arizona. Also, he maintains a water solubility database. --------------------------- Lowell Hall [hall@enc.edu] Dear Christian: I collaborate with Marc Parham of Interactive analysis, Bedford, MA. We have a model that is available for evaluation on a web site. The model is based on a very large database of experimental data. You can contact Marc at Marc Parham and view the site at www.InteractiveAnalysis.com The computation is very fast. --------------------------- Phil Howard [howardp@syrres.com] We have a program that predicts water solubility from octanol/water partition coefficient (see http://esc.syrres.com/interkow/wskow.htm) and it is available for free from the U.S.EPA (http://www.epa.gov/oppt/exposure/docs/episuitedl.htm). We are working on a program that will calculate water solubility using fragment constants that will be available soon. One of the nice features of this program is that it will allow one to calculate the water solubility from a close structural analog by using only the fragments that are different between the structural analog and the chemical of interest. We also have a database of water solubility data (see http://esc.syrres.com/interkow/PhysProp.htm) that has over 6000 water solubility values. This is available in a variety of formats including ISISBase; the latter allows substructure searching. --------------------------- J. W. McFarland [reckon.dat@attglobal.net] Dear Dr. Pilger: Here is a recent publication that describes one method and refers to some others that have been published. Some of these contain extensive datasets. Others have been published since. If you send me your address I will send you a reprint. McFarland, J. W.; Avdeef, A.; Berger, C. M.; Raevsky, O. A. Estimating the Water Solubilities of Crystalline Compounds from Their Chemical Structures Alone. J. Chem. Inf. Comput. Sci. 2001, 41(5), 1355-1359. --------------------------- Stephen Bowlus [stephen.bowlus@lionbioscience.com] The most extensive commercial effort I am aware of is ACD, which uses variants of the general solubility equation, with terms as surrogates for melting point where this is not known. Most of the models of which I am aware are based on the Yalkowsky model, or that is the one most frequently discussed in the literature. The main problem with it seems to be the melting point: there is limited utility to the model if you can't get an accurate estimate (i.e. measurement) of mp. So within this framework, methods to estimate mp are of great interest. A frequently overlooked program in this area is a group contribution method, Chemicalc (Suzuki & Kudo, JCAMD, 1990, 4, 155; Suzuki, JCAMD, 1991, 5, 149). I have used this mostly for logP estimation, so I can't comment on its strength for solubility, which it also calculates. The program is available > from QCPE, or I can send you the code for the PC (runs in a DOS window). From chemistry-request@server.ccl.net Thu Feb 21 03:59:32 2002 Received: from mail2.zrz.tu-berlin.de ([130.149.4.14]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id g1L8xW521289 for ; Thu, 21 Feb 2002 03:59:32 -0500 Received: from mailszrz.zrz.tu-berlin.de ([130.149.4.11]) by mail2.zrz.tu-berlin.de with esmtp (exim-3.35) id 16dp4C-0000ZZ-00; Thu, 21 Feb 2002 09:59:04 +0100 Received: from natrium.chem.tu-berlin.de ([130.149.169.143]) by mailszrz.zrz.tu-berlin.de with esmtp (exim-3.35) id 16dp49-00079P-00; Thu, 21 Feb 2002 09:59:01 +0100 Mime-Version: 1.0 X-Sender: chwu0531@mailszrz.zrz.tu-berlin.de Message-Id: In-Reply-To: <1014226904.3c73dfd8ed6eb@webmail.unige.ch> References: <1014226904.3c73dfd8ed6eb@webmail.unige.ch> Date: Thu, 21 Feb 2002 09:59:02 +0100 To: Pascal.Boulet@chiphy.unige.ch From: Christoph van =?iso-8859-1?Q?W=FCllen?= Subject: Re: CCL:Fwd: for Fermi and Coulomb holes Cc: chemistry@ccl.net Content-Type: text/plain; charset="iso-8859-1" ; format="flowed" Content-Transfer-Encoding: 8bit X-MIME-Autoconverted: from quoted-printable to 8bit by server.ccl.net id g1L8xW521290 >Dear CCL'ers, > >Recently, I've been asked a question about the difference between the Coulomb >hole and the Fermi hole. Could someone give me an answer? > In my opinion, the "fermi hole" comes along only by the pauli principle, that is, it is there even if there is no electron-electron interaction. The "coulomb hole" on the other hand vanishes if the electron interaction is switched off. Yours, +---------------------------------+----------------------------------+ | Prof. Christoph van Wüllen | Tele-Phone (+49) (0)30 314 27870 | | Technische Universität Sekr. C3 | Tele-Fax (+49) (0)30 314 23727 | | Straße des 17. Juni 135 | eMail | | D-10623 Berlin, Germany | Christoph.vanWullen@TU-Berlin.De | +---------------------------------+----------------------------------+ -- From chemistry-request@server.ccl.net Wed Feb 20 14:53:23 2002 Received: from mail.libertysurf.net ([213.36.80.91]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id g1KJrG531046 for ; Wed, 20 Feb 2002 14:53:16 -0500 Received: from gros-bill.lct.jussieu.fr (195.242.88.221) by mail.libertysurf.net (5.1.053) id 3C6C7B8000104EF4; Wed, 20 Feb 2002 20:52:41 +0100 Message-Id: <5.1.0.14.0.20020220200950.00a1a110@mailhost.lct.jussieu.fr> X-Sender: pollet@mailhost.lct.jussieu.fr (Unverified) X-Mailer: QUALCOMM Windows Eudora Version 5.1 Date: Wed, 20 Feb 2002 20:51:43 +0100 To: Pascal.Boulet@chiphy.unige.ch, chemistry@ccl.net From: Rodolphe Pollet Subject: Re: CCL:Fwd: for Fermi and Coulomb holes In-Reply-To: <1014226904.3c73dfd8ed6eb@webmail.unige.ch> Mime-Version: 1.0 Content-Type: text/plain; charset="us-ascii"; format=flowed >Here is my question: > >I have recently been reading "A Chemist's Guide to Density Functional >Theory". >On page 26 of the book the authors discuss the Fermi hole in terms of >pair density >and state that "Usually the exchange hole is largest around the probe >electron." > >Can anyone tell me why this is so? Why is it not largest at the >reference electron, >like the Coulomb hole? The Fermi hole is the exchange-hole and it is delocalized over the nuclei. Its shape resembles a localized orbital that would describe the bond, when the reference electron is in the corresponding bonding region. The simplest example is the H2 molecule, where the Fermi hole equals minus the HOMO density and is thus completely independent of the reference electron. Moreover, the Coulomb hole in molecules is not really centered around the reference electron but actually strongly depends on the position of the nucleus nearest to that electron. You can find more on this subject by searching for Buijse & Baerends articles. You will also soon find an article by me, A. Savin and F. Colonna in IJQC, where we show correlation holes along a nonlinear adiabatic connection path. --- R. Pollet pollet@pandora.saclay.cea.fr From chemistry-request@server.ccl.net Thu Feb 21 05:25:13 2002 Received: from hawk.dcu.ie ([136.206.1.5]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id g1LAPD523340 for ; Thu, 21 Feb 2002 05:25:13 -0500 Received: from dcu.ie (136.206.86.63) by hawk.dcu.ie (6.0.040) id 3C73AA2500007309 for chemistry@ccl.net; Thu, 21 Feb 2002 10:24:51 +0000 Message-ID: <3C74CAAC.AF2B806F@dcu.ie> Date: Thu, 21 Feb 2002 10:23:40 +0000 From: Dermot Brougham X-Mailer: Mozilla 4.73 [en] (Win98; I) X-Accept-Language: en MIME-Version: 1.0 To: chemistry@ccl.net Subject: teaching & software Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit Hi, Last year I asked ccl about free and commercial molecular modelling software for teaching. For better or for worse I bought Hyperchem in the end and ran a short lecture series/workshop which went quite well. I would like to extend this course to be a 36hr module to include drug design / virtual screening / docking. A few questions to anyone who has done something similar: 1. Is this appropriate undergrad fare? 2. What software would you recommend (whether free or commercial)? Note it must be windows based-I know this is a big limitation. 3. What is the best approach to teaching this sort of material? I will summarise if requested. Thanks, Dermot -- Dr. Dermot Brougham School of Chemical Sciences Dublin City University Dublin 9 Ireland Tel 353 1 7005472 Fax 353 1 7005503 From chemistry-request@server.ccl.net Thu Feb 21 09:13:51 2002 Received: from guppy.vub.ac.be ([134.184.129.2]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id g1LEDp530215 for ; Thu, 21 Feb 2002 09:13:51 -0500 Received: from mach.vub.ac.be (mach.vub.ac.be [134.184.129.3]) by guppy.vub.ac.be (8.9.1b+Sun/3.17.1.ap (guppy)) id PAA13804; Thu, 21 Feb 2002 15:12:42 +0100 (MET) for Received: from resu1.ulb.ac.be (resu1.ulb.ac.be [164.15.59.200]) by mach.vub.ac.be (8.9.3/3.13.3.ap (mach)) id PAA17914; Thu, 21 Feb 2002 15:13:28 +0100 (MET) for chemistry@ccl.net Date: Thu, 21 Feb 2002 15:13:28 +0100 (MET) Message-Id: <200202211413.PAA17914@mach.vub.ac.be> From: Pierre Mignon To: chemistry@ccl.net Subject: references for in-silico mutation calculations X-Mailer: Webmail ULB v2.1 Hello, I am interested in in-silico mutation calculations concerning biological systems, and I'd like to find a review or something fully detailed about it, does someone can give me such references ? Thank you in advance. Pierre Mignon PhD student in the Free University of Brussels (VUB) From chemistry-request@server.ccl.net Thu Feb 21 16:13:00 2002 Received: from chimail.cambridgehealth.com ([140.239.39.194]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id g1LLCx506958 for ; Thu, 21 Feb 2002 16:13:00 -0500 Received: by chimail.cambridgehealth.com from localhost (router,slmail V5.1); Thu, 21 Feb 2002 16:17:13 -0500 for Received: from edelo [140.239.39.147] by chimail.cambridgehealth.com [140.239.39.194] (SLmail 5.1.0.4420) with SMTP id 5F58138F01584CDB9AD389804E675B85 for ; Thu, 21 Feb 2002 16:17:12 -0500 Message-Id: <4.1.20020221160033.00bf2b60@140.239.39.194> X-Sender: eoregan@140.239.39.194 X-Mailer: QUALCOMM Windows Eudora Pro Version 4.1 Date: Thu, 21 Feb 2002 16:06:49 -0500 To: chemistry@ccl.net From: "Edel O'Regan" Subject: Cheminformatics and Structure-Based Drug Design conferences Mime-Version: 1.0 Content-Type: multipart/alternative; boundary="=====================_24229490==_.ALT" X-SLUIDL: BB95A230-F73342A2-92B7DB26-2DF3E407 --=====================_24229490==_.ALT Content-Type: text/plain; charset="us-ascii" Cambridge Healthtech Institute presents the: Second Annual Structure-Based Drug Design conference in April in Boston http://www.healthtech.com/2002/sbd/index.htm Sixth Annual Cheminformatics conference in May in Philadelphia http://www.chi-intelligentdrug.com/cin.asp Edel O'Regan Ph.D. Conference Producer Cambridge Healthtech Institute FAX: 617-630-1325 Phone: 617-630-1323 email: eoregan@healthtech.com --=====================_24229490==_.ALT Content-Type: text/html; charset="us-ascii" Cambridge Healthtech Institute presents the:

Second Annual Structure-Based Drug Design conference in April in Boston
        http://www.healthtech.com/2002/sbd/index.htm

Sixth Annual Cheminformatics conference in May in Philadelphia
        http://www.chi-intelligentdrug.com/cin.asp


Edel O'Regan Ph.D.
Conference Producer
Cambridge Healthtech Institute
FAX: 617-630-1325
Phone: 617-630-1323
email: eoregan@healthtech.com --=====================_24229490==_.ALT--