From chemistry-request@server.ccl.net Tue Aug 31 12:14:31 1999 Received: from syntem.eerie.fr (syntem.site-eerie.ema.fr [146.19.248.2]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id MAA04493 for ; Tue, 31 Aug 1999 12:14:30 -0400 Received: from syntem.eerie.fr (arginine.eerie.fr [146.19.248.6]) by syntem.eerie.fr (980427.SGI.8.8.8/980728.SGI.AUTOCF) via ESMTP id SAA37561; Tue, 31 Aug 1999 18:07:10 +0200 (MDT) Message-ID: <37CBFDDA.C5CE165C@syntem.eerie.fr> Date: Tue, 31 Aug 1999 18:07:54 +0200 From: Roger Lahana Reply-To: rlahana@syntem.eerie.fr Organization: Syntem X-Mailer: Mozilla 4.5 [en] (Win95; I) X-Accept-Language: en MIME-Version: 1.0 To: CCL , QSAR Society , CHMINF-L , Diversity List , Medicinal Chemistry List Subject: Drug-like inactive molecules Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit Dear colleagues, We are willing to assemble a database of drug-like molecules which have been shown experimentally to be inactive against a given type of target. By inactive, we mean that such molecules have been tested against a certain target and measured as significantly less active (preferably 2 logs lower) than what would be considered to be a 'hit'. All types of receptors are of interest. Actually, we could well nickname such a database the World Non-Drug Index, although we do not intend to use such a nickname for obvious copyright infringement reasons (we are very respectful of the work done at Derwent to maintain the World Drug Index). And, again, the molecules we are looking for should be drug-like. The purpose of such a database would be to have a reference data set of inactive compounds, so as to be able to compare them with the corresponding active molecules for any given receptor. Our intent is to make such a database publicly available, provided that the inactive data are sent to us on a non confidential basis. If you prefer however to transmit us data on a confidential basis, please contact us to discuss possible arrangements. Thank you for your collaboration. **************************************************************** Dr Roger Lahana Synt:em Vice-President R&D Parc Scientifique G.Besse Computational Drug Discovery 30000 Nimes email: rlahana@syntem.eerie.fr France Tel: +33 (0)466 048 666 Fax: +33 (0)466 048 667 **************************************************************** http://www.syntem.com **************************************************************** From chemistry-request@server.ccl.net Tue Aug 31 13:40:05 1999 Received: from ns.apbiotech.com (ns.apbiotech.com [192.36.117.130]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id NAA04882 for ; Tue, 31 Aug 1999 13:40:04 -0400 From: enrique.carredano@eu.apbiotech.com Received: from mailgate.se.apbiotech.com (unverified [193.235.253.52]) by ns.apbiotech.com (Rockliffe SMTPRA 3.3.1) with ESMTP id for ; Tue, 31 Aug 1999 19:33:25 +0200 Received: from eunotes.apbiotech.com (unverified [193.180.20.124]) by mailgate.se.apbiotech.com (Rockliffe SMTPRA 3.3.1) with SMTP id for ; Tue, 31 Aug 1999 19:29:33 +0200 Received: by eunotes.apbiotech.com(Lotus SMTP MTA v4.6.3 (778.2 1-4-1999)) id 412567DE.00658BC2 ; Tue, 31 Aug 1999 19:29:09 +0100 X-Lotus-FromDomain: XYNET To: chemistry@ccl.net Message-ID: <412567DE.00658A99.00@eunotes.apbiotech.com> Date: Tue, 31 Aug 1999 19:30:18 +0100 Subject: Re: CCL:effects of temperature on hydrophobicity Mime-Version: 1.0 Content-type: text/plain; charset=us-ascii Content-Disposition: inline Hi all CCLers I got some answers to my question regarding the the effects of temperature (say, an increase from 20 to 40 degrees C) on the hydrophobicity properties of a protein? I would like to thank Ricardo Mancera, Devapriya Choudhury, Anil Kumar Kandalam, Robert Bywater and Mike Gilson for their valuable answers. Here comes a summary Ricardo Mancera wrote Do a literature search on Privalov, he's done a lot of work on the temperature dependence of protein denaturation and hydrophobicity. It might be useful to look also for papers by Dill, Lee and Sharp. Devapriya Choudhury wrote Hydrophobicity, in general, increases with temperature. This has interesting consequences for protein folding (remember proteins are thought to fold due to hydrophobic collapse, this should be more pronounced at high temperature, paradoxically they unfold at high temperatures). There is a very nice review on this aspect by Peter l. Privalov. Check Adv. Prot. Chem. Mike Gilson wrote An increase in temperature is generally believed to enhance the hydrophobic effect, based upon data on the solvation of hydrophobic molecules (vacuum to water) as a function of temperature. In fact, that some proteins denature at cold temperatures is often attributed to the diminution of the hydrophobic effect at low temperature. I believe the Privalov review is the following. (I didn't find anything more recent by him in Adv. Prot. Chem.) PRIVALOV PL, GILL SJ STABILITY OF PROTEIN-STRUCTURE AND HYDROPHOBIC INTERACTION ADV PROTEIN CHEM 39: 191-234 1988 I also recommend a recent analysis from Schellman, both for the paper itself and for the references it contains: "Temperature, Stability,and the Hydrophobic Interaction" Biophys. J. 73:2960-64, 1997. Anil Kumar Kandalam wrote With an increase in temperature in the range of 20-40C, there is change in the confirmational folding of the amino rather an imino acid PROLINE which would maintain the protein stable, with an increased stability of the protein as a function of its hydrophobic microenvironment in all those proteins where proline happens to be an essential component of the protein. In those proteins which do not have the iminoacid proline as a component, the activity regulation of the protein as a function of temperature where activation of the active sites of the protein is far more greater in comparison to deactivation. In general, majority of the proteins after their synthesis, fold in a cooperative fashion which demands the natural physiological conditions as it involves nothing but the interaction of aminoacids. Hence the temperature increase within the physiological range would facilitate easy folding by the increased interactions between the activated hydrophobic aminoacids. Robert Bywater wrote It depends on what you mean by a hydrophobic property. The following can all be ascribed, at least in part, to 'hydrophobic interactions' : - protein folding - ligand-protein interactions - protein-protein interactions - insertion of membrane proteins into membrane If by hydrophobic property you mean interactions between nonpolar surfaces that are enhanced by exclusion of water (the 'standard' definition of 'hydrophobic interaction') then since the latter is associated with an increase in entropy there will be a reduction in the overall free energy and because of delta(G) = delta(H) - T.delta(S) this effect will increase linearly with temperature. NB other types of interaction such as hydrogen bonding and ion-pairing also require desolvation to take place so this entropic contribution is by no means exclusive to the 'hydrophobic interaction'. __________________________ Thank you again for your contributions. Enrique Enrique Carredano, MSc, PhD +46 (0)18 16 50 00 tel Polymer and Surface Chemistry +46 (0)18 16 50 42 direct Amersham Pharmacia Biotech +46 (0)18 16 63 96 fax Bjorkg 30, 751 84 Uppsala Sweden enrique.carredano@eu.apbiotech.com From chemistry-request@server.ccl.net Tue Aug 31 18:42:21 1999 Received: from pegasus.arc.nasa.gov (pegasus.arc.nasa.gov [128.102.199.140]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id SAA00910 for ; Tue, 31 Aug 1999 18:42:21 -0400 Received: (from ricca@localhost) by pegasus.arc.nasa.gov (8.9.1/8.9.1) id PAA06724 for chemistry@ccl.net; Tue, 31 Aug 1999 15:38:41 -0700 (PDT) Date: Tue, 31 Aug 1999 15:38:41 -0700 (PDT) From: Alessandra Ricca Message-Id: <199908312238.PAA06724@pegasus.arc.nasa.gov> To: chemistry@ccl.net Hi all, I am looking for a QM/MD code (free or commercial) to study the interaction between gas phase molecules and a surface. In particular I would like to run NVT simulations using a bath (300 K) coupled to the surface and imposing a given velocity to the incoming gas phase molecules. As a QM I would like to use DFT (non local). Thanks. I will summarize. Alessandra Alessandra Ricca Mail: Thermosciences Institute Senior Research Scientist NASA Ames Research Center ELORET Corporation Mail Stop 230-3 http://www.eloret.com Moffett Field, CA 94035-1000 From chemistry-request@server.ccl.net Wed Sep 1 07:10:43 1999 Received: from ccl.net (atlantis.ccl.net [192.148.249.4]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id HAA04505 for ; Wed, 1 Sep 1999 07:10:43 -0400 Received: from RBAD33.RBACRXCLU.BAS.ROCHE.COM (mail-external-basel.bas.roche.com [196.3.50.190]) by ccl.net (8.8.6/8.8.6/OSC 1.1) with ESMTP id HAA13416 for ; Wed, 1 Sep 1999 07:06:58 -0400 (EDT) Received: from rbamsemcn1.bas.roche.com (rbamsemcn1.bas.roche.com [145.245.211.139]) by Roche.COM (PMDF V5.2-31 #33472) with ESMTP id <01JFGGSR8DGK9DPWNN@Roche.COM> for chemistry@www.ccl.net; Wed, 1 Sep 1999 13:06:17 +0200 Received: by rbamsemcn1.bas.roche.com with Internet Mail Service (5.5.2448.0) id ; Wed, 01 Sep 1999 13:06:02 +0200 Content-return: allowed Date: Wed, 01 Sep 1999 13:06:13 +0200 From: "Sherborne, Brad {DISC~Welwyn}" Subject: RE: FW: Drug-like inactive molecules To: "'rlahana@syntem.eerie.fr'" , "Arthur M. Doweyko" Cc: QSAR Society , CCL Message-id: <431EB483DFB4D111A2D50000F843C5C4011E5AC8@rwemsem2.wel.roche.com> MIME-version: 1.0 X-Mailer: Internet Mail Service (5.5.2448.0) Content-type: text/plain; CHARSET=US-ASCII I hope that this advances debate! Would it be more sensible for Roger's purpose to strive for SETS of compounds that span >= 2 log units (activity and inactivity). There are too many compounds that are inactive against a particular target (shades of the diversity debate here), as anyone working in industry can testify. SETS are obviously then up for discussion, but I'd apply a general classifier of chemically congeneric. These would then likely be covered in the same patent, where such data is sometimes available. Personally I'd see a greater importance in a "Non-drug Index" database for focussing on congeneric sets of compounds that span bioavailable and non-bioavailable, adverse effects and safe, etc. I'm not sure whether this data would be covered to any extent in public literature. All the best Brad > Brad Sherborne Registered address > Roche Products Limited > Roche Discovery Welwyn 40 Broadwater Road > * Phone : (+44) 01707 366551 Welwyn Garden City > * Fax No : (+44) 01707 366907 Hertfordshire AL7 3AY > * e-mail : Brad.Sherborne@roche.com Registration Number 100674 > From chemistry-request@server.ccl.net Wed Sep 1 07:39:41 1999 Received: from tdsede-exg.tdsede.dom ([194.235.134.141]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id HAA04633 for ; Wed, 1 Sep 1999 07:39:40 -0400 Received: by TDSEDE.EXG with Internet Mail Service (5.5.2232.9) id ; Wed, 1 Sep 1999 12:33:53 +0100 Message-ID: <314CB0E40556D2118D930000C07CAAF66549@TDSEDE.EXG> From: Paulo Couto To: "'chemistry@ccl.net'" Subject: Marching Cube File Format Date: Wed, 1 Sep 1999 12:33:51 +0100 MIME-Version: 1.0 X-Mailer: Internet Mail Service (5.5.2232.9) Content-Type: text/plain Dear CCL members I wonder if there is any w95/98 molecular visualization package that can read data from marching cubes format files and plot isovalue surfaces. An alternative would be a conversion utility to g94 cube file format. Can anyone help me with this? Thanks in advance Best Regards Paulo Couto ( pauloc@tduarte.pt ) + -----------------------------------------------------------------------+ | Unix is user friendly, it simply chooses its friends wisely ! | + -----------------------------------------------------------------------+ From chemistry-request@server.ccl.net Wed Sep 1 09:59:43 1999 Received: from arnold.chem.uoa.gr (arnold.chem.uoa.gr [195.134.76.50]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id JAA05158 for ; Wed, 1 Sep 1999 09:59:41 -0400 Received: from localhost (jkerk@localhost) by arnold.chem.uoa.gr (8.8.8/8.8.8) with SMTP id QAA11819 for ; Wed, 1 Sep 1999 16:48:38 +0300 (EET DST) Date: Wed, 1 Sep 1999 16:48:38 +0300 (EET DST) From: John Kerkines To: chemistry@ccl.net Subject: v.A. Fock Message-ID: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Dear friends, Does anybody remember when (and where) Vladimir Fock died? I know that he was born in 1898, and I seem to remember that he died in 1980 but I am not sure about it. Thanks John From chemistry-request@server.ccl.net Wed Sep 1 06:22:37 1999 Received: from ccl.net (atlantis.ccl.net [192.148.249.4]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id GAA03497 for ; Wed, 1 Sep 1999 06:22:37 -0400 Received: from syntem.eerie.fr (syntem.site-eerie.ema.fr [146.19.248.2]) by ccl.net (8.8.6/8.8.6/OSC 1.1) with ESMTP id GAA13009 for ; Wed, 1 Sep 1999 06:18:53 -0400 (EDT) Received: from syntem.eerie.fr (arginine.eerie.fr [146.19.248.6]) by syntem.eerie.fr (980427.SGI.8.8.8/980728.SGI.AUTOCF) via ESMTP id MAA45976; Wed, 1 Sep 1999 12:18:02 +0200 (MDT) Message-ID: <37CCFD88.FF1CC137@syntem.eerie.fr> Date: Wed, 01 Sep 1999 12:18:48 +0200 From: Roger Lahana Reply-To: rlahana@syntem.eerie.fr Organization: Syntem X-Mailer: Mozilla 4.5 [en] (Win95; I) X-Accept-Language: en MIME-Version: 1.0 To: "Arthur M. Doweyko" CC: rlahana@syntem.eerie.fr, QSAR Society , CCL Subject: Re: FW: Drug-like inactive molecules References: <37CCD96B.5E859B9@syntem.eerie.fr> <37CCF220.88D333F@cris.com> Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit Arthur, "Arthur M. Doweyko" wrote: > No company in their right mind would release any structural information in their > database. Your idea seems reasonable, but only without thinking of the > ramifications. Thank you for your contribution to this debate. As you maybe noticed, I am also working in a company, so I certainly know what you mean. And as you certainly noticed as well, our intent again is to make all these data publicly available. Should my request be targeted at pharmaceutical companies, I would certainly not use public discussion lists and I would certainly not announce that we would make the collected data publicly available. Clearly, this initiative is mainly addressed to academic scientists, as it should appear after thinking of the ramifications. Regards, Roger From chemistry-request@server.ccl.net Wed Sep 1 03:48:30 1999 Received: from ccl.net (atlantis.ccl.net [192.148.249.4]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id DAA02887 for ; Wed, 1 Sep 1999 03:48:30 -0400 Received: from syntem.eerie.fr (syntem.site-eerie.ema.fr [146.19.248.2]) by ccl.net (8.8.6/8.8.6/OSC 1.1) with ESMTP id DAA11653 for ; Wed, 1 Sep 1999 03:44:48 -0400 (EDT) Received: from syntem.eerie.fr (arginine.eerie.fr [146.19.248.6]) by syntem.eerie.fr (980427.SGI.8.8.8/980728.SGI.AUTOCF) via ESMTP id JAA42591; Wed, 1 Sep 1999 09:43:59 +0200 (MDT) Message-ID: <37CCD96B.5E859B9@syntem.eerie.fr> Date: Wed, 01 Sep 1999 09:44:44 +0200 From: Roger Lahana Reply-To: rlahana@syntem.eerie.fr Organization: Syntem X-Mailer: Mozilla 4.5 [en] (Win95; I) X-Accept-Language: en MIME-Version: 1.0 To: han_waterbeemd@sandwich.pfizer.com, QSAR Society , CCL Subject: Re: FW: Drug-like inactive molecules References: Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit Dear Han, han_waterbeemd@sandwich.pfizer.com wrote: > What is not a hit today may be one tomorrow! Thank you for this sensible comment, which gives me the opportunity to clarify this point: what is not a hit today *on a given target* may be one tomorrow *on another one*! Therefore, we would record this molecule in our database as a non-hit for the target(s) where it has been shown it is not a hit. The fact that it could become a hit on something different would not be in the scope of the database. To some extent, if it is indeed active on some other targets, then it should be in the WDI or other similar databases. The idea really is to be able to get for any given target a list of measured non-hits. It is not to say that molecules in such a database are inactive against every present and future target. A good example of this is Cocaine, which is indeed in the WDI for its well-known CNS activity, but which has been measured as inactive on the histamine H1 receptor. Cocaine would then be referenced as "inactive on H1". Roger **************************************************************** Dr Roger Lahana Synt:em Vice-President R&D Parc Scientifique G.Besse Computational Drug Discovery 30000 Nimes email: rlahana@syntem.eerie.fr France Tel: +33 (0)466 048 666 Fax: +33 (0)466 048 667 **************************************************************** http://www.syntem.com **************************************************************** From chemistry-request@server.ccl.net Wed Sep 1 17:24:07 1999 Received: from lucia.u.arizona.edu (mcafiero@lucia.U.Arizona.EDU [128.196.137.26]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id RAA08210 for ; Wed, 1 Sep 1999 17:24:06 -0400 Received: from localhost (mcafiero@localhost) by lucia.u.arizona.edu (8.8.8/8.8.8) with ESMTP id OAA40086; Wed, 1 Sep 1999 14:20:10 -0700 Date: Wed, 1 Sep 1999 14:20:10 -0700 (MST) From: Mauricio L Cafiero To: John Kerkines cc: chemistry@ccl.net Subject: Re: CCL:v.A. Fock In-Reply-To: Message-ID: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Hello: He died in 1974. Mauricio Cafiero Graduate Student: Theoretical and Computational Quantum Chemistry Dept. of Chemistry University of Arizona Tucson, AZ From chemistry-request@server.ccl.net Wed Sep 1 21:10:55 1999 Received: from mail.telis.org (mail.telis.org [209.142.0.15]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id VAA09016 for ; Wed, 1 Sep 1999 21:10:54 -0400 Received: from [207.49.121.222] (s01-pm16.snaustel.campuscwix.net [207.49.121.222]) by mail.telis.org (8.9.3/8.9.3) with ESMTP id SAA31205 for ; Wed, 1 Sep 1999 18:06:22 -0700 X-Sender: gammadas@mail.telis.org Message-Id: Mime-Version: 1.0 Content-Type: text/plain; charset="us-ascii" Date: Wed, 1 Sep 1999 20:09:13 -0500 To: chemistry@ccl.net From: Goutam Das Subject: new email address To CCL: Please send mail to my new email address: "gammadas@netscape.net" Thank you. GOUTAM DAS Research Scientist BETZDEARBORN (A division of Hercules) PO BOX 4300, 9669 GROGANS MILL ROAD THE WOODLANDS, TX 77387-4300, USA # 281.367.6201 xt 425/409 email:gammadas@telis.org; gammadas@netscape.net