From owner-chemistry@ccl.net Wed Jun 28 02:22:30 1995 Received: from dingo.cc.uq.oz.au for M.Dooley@mailbox.uq.oz.au by www.ccl.net (8.6.10/930601.1506) id CAA03229; Wed, 28 Jun 1995 02:18:46 -0400 Received: from localhost by dingo.cc.uq.oz.au with SMTP id AA01681 (5.67a/IDA-1.5 for ); Wed, 28 Jun 1995 16:18:44 +1000 Date: Wed, 28 Jun 1995 16:18:37 +1000 (GMT+1000) From: Michael Dooley X-Sender: ddmdoole@dingo.cc.uq.oz.au To: Compuational Chemistry List Subject: Re:POSTED RESPONSES: Quantitative assessment of novel ligands Message-Id: Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Dear Netters, Thanks to everyone who responded to my query >I'm searching for a protocol or recipe of 'vital statistics' to assess >novel ligands that i've designed, so that i'll have firm arguments to >convince organic chemists to synthesise a molecule. I'm using biosym >software + intuition to de novo design ligands for a target with good >x-ray data and also have access to Oxford Molecular software. If it >might not be possible to roughly predict binding constants for novel >compounds that differ greatly from known ligands, are there methods to >predict the effects of modifications to known ligands. I'm aware of >scoring functions such as Bohm Comput-aided mol des (1994) 243, but I'm >not sure if this would be appropriate. Eagerly awaiting any suggestions. ************************************************************************* Michael, We have done some preliminary work on assessing binding energies as calculated from a series of molecular dynamics runs of an inhibitor bound to the active site of Influenza sialidase. This can be found in J Med Chem 37, 616 (1994) and the work was done by a colleague Neil Taylor. A more comprehensive paper is at the moment being reviewed for publication in J Comp Chem, but I'm not sure when that will published. I have adapted the protocol Neil developed to several other Sialidase's and have obtained reasonable results that enable me to at least say whether a compound is worth proceeding with. The protocol involves a series of molecular dynamics runs on the inhibitor docked into the active site of the protein/enzyme of interest and then determining the pairwise non-bonded interaction energy between the inhibitor and the protein. This enables me to determine a set relative binding energies. i.e. compound A > compound B >> compound c = compound d. Both Neil and I will hopefully be presenting results at the drug-design conference later in the year in Cairns. I forgot to mention we used Biosym's InsightII and Discover for the calculations and viewing of the results. Bye Jeff. -- Jeff Dyason Department of Medicinal Chemistry, Victorian College of Pharmacy, Ph: 61 3 9903-9110 Monash University, Parkville, Fax: 61 3 9903-9582 Melbourne Victoria Australia e-mail: jcd@vcp.monash.edu.au ****************************************************************************** Dear Michael Dooley. As you are undoubtedly aware there are no simple solutions to your problem. And the problem is not unique to you, everyone in drug design faces it. I have just a few comments to make: We have implemented Boehm's LUDI scoring algorithm (in Sybyl), and find it somewhat unsatisfactory because it is overly sensitive to the positions of the atoms, and the hydrogens in particular. Also, one could wish to make a more sophisticated distinction between various types of hydrogen bonds. An inherent deficiency in considering the ligand/protein complex is that the ligand/water (and protein/water) complexes are equally important. To my knowledge the only proper way to treat this is by means of free energy perturbation calculations (simulations). Which means hard work or (and ?) good luck to get decent results. Chemical intuition is likely to be your best tool. (although an analysis tool like Goodford's GRID is helpful) But you and your synthetic chemists have to accept that our ability to predict is not perfect, - it is probably more like that of the meteorologist making his weather forecast: better than random. Sorry, if this sounds awfully pessimistic. Cheers, Leif Norskov Novo Nordisk A/S Copenhagen Denmark lnl@novo.dk ******************************************************************************** In response to your question - 'what molecular parameters can be generated to convince an organic chemist to synthesise a molecule you have designed?' Before embarking on this process you should also view the question from the organic chemists point of view. He will be considering your compound and prioritising it with other compounds he is already synthesising and will probably make this assessment based on i) synthesisability (a major problem with de novo designed ligands) ii) the state of the project (is it early days and leads are scarce, or is it towards the end of the project when fine tuning is the focus?) iii) how far is the structure away from the known SAR iv) in the light of ii and iii what are the chances of success and are the risks worth taking. There are probably other questions, but I doubt whether any other parameters will make a great difference to your ability to persuade a busy organic chemist to synthesise your compounds. Presumably you are convinced that the molecules you have designed are worth making, therefore your best approach is to present your argument based on how you have designed the molecules, but most important of all, you should have your chemist collaborators on board at an early stage in the modelling and involve them as much as possible in the process. Along with the basic tenet of modelling: 'No modelling without experimentation' (A. Vintner) we should possibly add: 'No synthesis without dialog' ?! If you are not convinced yourself that these molecules are worth making and that their synthesis will answer this question, then you need to get into activity prediction, i.e. QSAR using MOPAC generated parameters, principal component analysis etc, or using Comfa (Tripos). These are not trivial exercises but do give a prediction that may help to decide whether the molecules are worth synthesising. Good luck anyway! Chris Snell Molecular Modelling and Computational Chemistry Sandoz Institute for Medical Research 5 Gower Place London WC1E 6BN E-Mail snell@sandoz.com Tel 0171-333-2165 Fax 0171-387-4116 ******************************************************************************* Michael, A program from edusoft called HINT (Hydrophobic Interactions) will give a rough estimate for the binding constant of a ligand/protein complex. The www address is a follows: http://www.i2020.net/edusoft/hint.html The nice thing about this program is the "pretty" pictures that can be generated in order to "validate" your claim for ligand synthesis. In my experience most synthetic organic chemists seem to love color graphics and are usually willing to bend over backwards to assist you with your problem once you provide them with some justification. The software currently interfaces with InsightII, Sybyl, and Chem-X. Also, QSAR analysis can carry alot of weight with synthetic organic chemists (a standard module in most software packages). I would suggest that COMFA QSAR would carry more weight than standard QSAR. Furthermore, HINT can be used as an additional COMFA field with QSAR within Sybyl. If I can provide further assistance, please drop me a line. As a side note, do you know how difficult it is to obtain a post-doctoral position in your neck of the woods? I hope that I have been of some help, Shawn Feaster University of Iowa Dept. of Chemistry feaster@tessa.iaf.uiowa.edu ****************************************************************************** There are probably over a hundred citations for the use of CoMFA as a tool for predicting biological activities (conversely I know of none for BioSym or Oxford Molecular save that of Boehm and Richards, the developers). If you are involved with known receptor structures, some of the work by Garland Marshall and his collaborators, for example in JACS, might be relevant. Sorry I don't have specific referebnces handy -- yet another biased developer, Dick Cramer cramer@xhost3.tripos.com ****************************************************************************** A variety of QSAR techniques have been developed for the purpose of predicting the activity of ligands. CoMFA, comparative molecular field analysis, is a relatively new technique which was developed by Dick Cramer of Tripos. There is a catch. Tripos holds a patent on the method and you need a license for Sybyl for the job. CoMFA involves the following steps: 1) Generate a set of molecules (learning set + set of new molecules) and superimpose them. The hard step is deciding on a reasonable conformation and determining which atoms to use in the superposition. You also need to calculate the charges on the molecule. MOPAC with the AM1 Hamiltonian works well. 2) You save the set of molecules with charges in a molecular database. 3) Each molecule in the database is imbedded in a three-dimensional grid. A charged probe molecule is placed at each point in the grid and the interaction energy between the probe and the ligand is calculated at each grid point. The three-dimensional matrix of energy values, one per grid point, is called a field. Tripos' software divides the energy calculation into two parts: a steric portion based on van der Waals interactions and an electrostatic part. 4) In the last step, you correlate the biological or chemical activity of the ligands with the field values. In effect, each energy at each grid point corresponds to an "independent variable" so the number of independent variables far exceeds the number of molecules in the database. Hence the method of partial least squares (PLS) is required to construct the model. In the PLS algorithm, linear combination(s) of the field values is(are) calculated which best explain the data. These linear combinations are the new independent variables and are called components. 5) With these components in hand, you can predict the activity of the new ligands. I don't guarantee success. The Martin group at Abbott and the Kubinyi group at BASF have had extensive experience with the method. CoMFA did quite well in modelling logP of amino acids. I am finishing up a CoMFA analysis of inhibitors of a serine protease for the Hansch group at Pomona. Wayne Steinmetz ******************************************************************************** I would be very interested to receive a summary of replies. We face similar problems for the assessment of novel ligands. We have found variants of Bohm's scoring function useful in conjunction with simple simulation protocols to check the ligand binds as expected. The problem is that if your set of designs bind differently and/or have very different chemistry, one needs to have alot of faith in the ability of current methods to differentiate between them. However reparametrising Bohm-like scoring functions to agree with experimental data for the receptor you're interested in should be effective. Of course this isn't always possible. There's a recent paper by people at Merck who correlated interaction energies with binding affinities when designing HIV protease inhibitors and they got nice results. with thanks chris Chris Murray | Proteus Molecular Design Ltd., | Tel: 01625-500555 Lyme Green Business Park, | Fax: 01625-500666 Macclesfield, Cheshire, | Email: C.W.Murray@proteus.co.uk SK11 0JL, UK | ********************************************************************************* Dear Michael, According to your question in CCL about tools for the ligands design, I want to turn your attention to the program Apex-3D integrated with insightII (BIOSYM). It allows among other things to build 3D QSAR models and predict binding constants for novel compounds. A short description of the methods incorporated into Apex-3D can be found in the http://www.dcl.co.il/apex3d.html. More detailed description is in the Apex-3D Manual available from BIOSYM. Please feel free to contact me for additional information. Sincerely yours Boris Vesterman *---------------------------------------------------* | Boris Vesterman, Ph.D. | | | | DCL Systems International Ltd. | | 20 Galgalei Haplada St. Herzlia Industrial Area | | P.O.B. 544 Herzlia 46105 Israel | | Phone: 972-9-584684 | | Fax: 972-9-543917 | | E-mail: boris@dcl.co.il | *---------------------------------------------------* ********************************************************************************* If you have a set of related molecules you might be successful with CoMFA. The best references are to Garland Marshall in J. Med. Chem. His group did several different test cases. You could do the calculations with Oxford Molecular ASP/TSAR. Let me know what other answers you get. @@@@@@@@@@@ Yvonne Martin, Senior Project Leader @ Computer Assisted Molecular Design Project @@@@@@@@ @ D-47E, AP10 2fl @ @ Abbott Laboratories @ @ 100 Abbott Park Road @@@@@@@@@@ Abbott Park, IL 60064-3500 Phone: 708 937-5362 FAX: 708 937-2625 yvonne.martin@abbott.com Andy McCammon wrote a nice review article: (1) Straatsma, T. P.; McCammon, J. A., "Theroetical Calculations of Relative Affinities of Binding," Methods in Enzymology 1991, 202, 497-511. yvonne.martin@abbott.com ****************************************************************************** ***************************************************************************** I further e-mailed Boris (below) and his speedy reply is printed at bottom. Thanks Boris! >Dear Boris, > Thankyou for your fast reply to my query on quantit. asess. >novel ligands. On the subject of Apex-3D, a member of our group >has investigated the application of this software to our problem. >This avenue is still under investig. but this is our No 1 problem: > we have many crystal structures of target and ligand and so have very >good information on overlays of different ligands. Apex-3D wants to >manipulate our data set away from reality to suit its own ideas on how >the ligands should align, which seems like a backwards step! Any ideas? >Cheers >Michael Dooley Michael, I am familiar with this problem. When Apex-3D was created most of the attention was paid to the "black box" approach, when no X-ray data are available for enzyme-ligand complex. Unfortunately in case when you have additional information about crystal structures of target and ligand, Apex-3D still tries to generate its own superposition hypothesis. You can reduce this list of different biophores by selection of most appropriate Task Definition parameters and tolerances. I mean the following: to describe atom_class's and atom_property's for the specific ligand groups, reduce tolerance ( as narrow as possible ) to decrease the number of possible alignments. May be in some cases it is not so simple, and I'll be happy to answer any questions you have. BTW, this autumn Apex-3D new version will be shipped ( integrated with InsightII v.95.0. There is a set of tools for much flexible task definition and user control of biophore and model selection. A special tool that is currently under development can help to solve your problem. It allows to create a biophore from a user defined superposition. All your suggestion in this direction are highly appreciated. Best Regards Boris Vesterman *---------------------------------------------------* | Boris Vesterman, Ph.D. | | | | DCL Systems International Ltd. | | 20 Galgalei Haplada St. Herzlia Industrial Area | | P.O.B. 544 Herzlia 46105 Israel | | Phone: 972-9-584684 | | Fax: 972-9-543917 | | E-mail: boris@dcl.co.il | *---------------------------------------------------* **************************************************************************** From owner-chemistry@ccl.net Wed Jun 28 03:07:29 1995 Received: from jazz.ucc.uno.edu for JSMCM@jazz.ucc.uno.edu by www.ccl.net (8.6.10/930601.1506) id CAA03907; Wed, 28 Jun 1995 02:53:51 -0400 Received: from jazz.ucc.uno.edu by jazz.ucc.uno.edu (PMDF #2820 ) id <01HS7I7R520K8ZLZNC@jazz.ucc.uno.edu>; Tue, 27 Jun 1995 17:18:57 CST Date: 27 Jun 1995 17:18:57 -0600 (CST) From: JORGE Subject: Re: CCL:Ab-initio Force Constants To: dcav@loriot.lsmc.u-bordeaux.fr Cc: chemistry@ccl.net Message-id: <01HS7I7R520M8ZLZNC@jazz.ucc.uno.edu> X-VMS-To: IN%"dcav@loriot.lsmc.u-bordeaux.fr" X-VMS-Cc: IN%"chemistry@ccl.net" ,JSMCM MIME-version: 1.0 Content-type: TEXT/PLAIN; CHARSET=US-ASCII Content-transfer-encoding: 7BIT Regarding: >dcav@loriot.lsmc.u-bordeaux.fr >Ab-initio frequency calculations give >force constants in cartesian and internal >coordinates, the units being respectively >hartree/bohr (and not hartree/bohr**2) and >atomic units. Does somebody know how to >convert them in mdyn/angstrom? Actually, the units of force constant are Ha/bohr**2 the conversion to mdyn/A**2 is 1 mdyn/A = 0.0642305 Ha/bohr**2 Best regards Jorge ********************************************************************* * * * * Dr. Jorge M. Seminario * e-mail: jsmcm@uno.edu * * Assistant Professor for Research * jsmcm@jazz.ucc.uno.edu * * Department of Chemistry * Phone: 504-286-7216 (off.) * * University of New Orleans * Fax: 504-286-6860 (off.) * * New Orleans, Louisiana 70148 * phone: 504-834-1927 (home) * * USA * * * * * ********************************************************************* From owner-chemistry@ccl.net Wed Jun 28 04:37:35 1995 Received: from hearnvax.nic.surfnet.nl for J.Nilsson@farm.RUG.NL by www.ccl.net (8.6.10/930601.1506) id EAA04630; Wed, 28 Jun 1995 04:25:50 -0400 Received: from mailhost.rug.nl by HEARNVAX.nic.SURFnet.nl (PMDF V4.2-12 #3330) id <01HS8IHFMW8000FRGC@HEARNVAX.nic.SURFnet.nl>; Wed, 28 Jun 1995 10:25:33 +0200 (MET-DST) Received: from dep.farm.rug.nl by mailhost.rug.nl with SMTP (PP); Wed, 28 Jun 1995 10:25:36 +0200 Received: from novell_farm1.farm.rug.nl by dep.farm.rug.nl (KAA05129); Wed, 28 Jun 1995 10:21:15 +0200 Received: from FARM1/MAIL by novell_farm1.farm.rug.nl (Mercury 1.20); 28 Jun 95 10:24:39 MET Received: from MAIL by FARM1 (Mercury 1.20); 28 Jun 95 10:24:19 MET Date: Wed, 28 Jun 1995 10:24:18 +0100 (CET) From: Jonas Nilsson Subject: CoMFA patent? To: chemistry@ccl.net Message-id: <914BEF0940@novell_farm1.farm.rug.nl> Organization: Pharmacy Dept Groningen University X-Envelope-to: chemistry@ccl.net X-Mailer: Pegasus Mail for Windows (v2.01) Content-transfer-encoding: 7BIT Priority: normal Dear Netters, In the summary from Michael Dooley, Wayne Steinmetz claims that there is a patent for CoMFA as a method. What exactly stands in this patent? If there is such a patent, where can I get a copy of the official patent documents? Thanks in advance, Jonas Nilsson Dep of Med Chemistry Groningen, The Netherlands E-mail: j.nilsson@farm.rug.nl From owner-chemistry@ccl.net Wed Jun 28 06:37:33 1995 Received: from disperse.demon.co.uk for davel@chmqst.demon.co.uk by www.ccl.net (8.6.10/930601.1506) id GAA06150; Wed, 28 Jun 1995 06:35:02 -0400 Received: from post.demon.co.uk by disperse.demon.co.uk id aa25337; 28 Jun 95 11:00 +0100 Received: from chmqst.demon.co.uk by post.demon.co.uk id aa11918; 28 Jun 95 11:00 +0100 From: David Livingstone Organization: ChemQuest To: chemistry@ccl.net Date: Wed, 28 Jun 1995 08:40:54 +0100 Subject: CCL:Quantitaive Assessment of Novel ligands CC: m.dooley@mailbox.uq.oz.au Priority: normal X-mailer: Pegasus Mail for Windows (v2.01) Message-ID: <9506281100.aa11918@post.demon.co.uk> Hi, Michael Dooley asked the question: "I'm searching for a protocol or recipe of 'vital statistics' to assess novel ligands that i've designed, so that i'll have firm arguments to convince organic chemists to synthesise a molecule. I'm using biosym software +....." There are probably as many ways to do this as there are chemists that you work with but I think that Chris Snell from Sandoz put his finger on it; " ........... but most important of all, you should have your chemist collaborators on board at an early stage in the modelling and involve them as much as possible in the process." Nobody likes to be told what to do and it is often very easy to hide some very good reasons behind a lot of gobbledegook. Let the chemists play with your toys and they will be convinced themselves. I have always found that this approach works best. Regards, Dave. ------------------------------------------------------------------ D.J. Livingstone ChemQuest Cheyney House, 19-21 Cheyney St., Steeple Morden. Herts UK SG8 0LP Phone & Fax: +44 (0)1763 852569 e-mail davel@chmqst.demon.co.uk ------------------------------------------------------------------ From owner-chemistry@ccl.net Wed Jun 28 07:22:34 1995 Received: from rzusuntk.unizh.ch for toukie@zui.unizh.ch by www.ccl.net (8.6.10/930601.1506) id HAA06616; Wed, 28 Jun 1995 07:15:05 -0400 From: Received: from rzurs3.unizh.ch by rzusuntk.unizh.ch (4.1/SMI-4.1.9) id AA13674; Wed, 28 Jun 95 13:15:02 +0200 Received: by rzurs3.unizh.ch (AIX 3.2/UCB 5.64/4.03) id AA44597; Wed, 28 Jun 1995 13:15:02 +0200 Message-Id: <9506281115.AA44597@rzurs3.unizh.ch> Subject: MacroModel w/ Linux OS? To: chemistry@ccl.net Date: Wed, 28 Jun 1995 13:15:01 +0200 (MEST) X-Mailer: ELM [version 2.4 PL24 PGP2] Content-Type: text Content-Length: 500 Dear Colleagues; If anyone has succeeded in getting the programme MacroModel to run under the Linux operating system, I would be most grateful if you would contact me. Thanks in advance for your cooperation. Sincerely, (Dr.) S. Shapiro Institut fuer orale Mikrobiologie und allgemeine Immunologie Zentrum fuer Zahn-, Mund- und Kieferheilkunde der Universitaet Zuerich Plattenstrasse 11 Postfach CH-8028 Zuerich 7 Switzerland Internet: toukie@zui.unizh.ch FAX-nr: ( ... + 1) 261'56'83 From owner-chemistry@ccl.net Wed Jun 28 07:37:34 1995 Received: from enar.organik.uni-erlangen.de for jens@EROS.CCC.Uni-Erlangen.DE by www.ccl.net (8.6.10/930601.1506) id HAA06669; Wed, 28 Jun 1995 07:21:27 -0400 Received: from kochab.erosnet (kochab.organik.uni-erlangen.de) by enar.organik.uni-erlangen.de with SMTP id AA06078 for CHEMISTRY@ccl.net (5.65c/IDA-1.4.4/bs-02); Wed, 28 Jun 1995 13:09:07 +0200 Received: by kochab.erosnet (5.x/SMI-4.1/client) id AA13515; Wed, 28 Jun 1995 13:09:05 +0200 Date: Wed, 28 Jun 1995 13:09:05 +0200 From: Jens.Sadowski@EROS.CCC.Uni-Erlangen.DE Message-Id: <9506281109.AA13515@kochab.erosnet> To: CHEMISTRY@ccl.net, gdch-cic@EROS.CCC.Uni-Erlangen.DE Subject: Corina: 2D-to-3D Mail Server Cc: jens@EROS.CCC.Uni-Erlangen.DE X-Sun-Charset: US-ASCII Corina: 2D-to-3D Mail Server ---------------------------- We offer free access to our 2D-to-3D conversion program Corina via email. Just mail your structures and Corina returns the 3D-atomic coordinates. Every user has 1000 structures free. More information at http://schiele.organik.uni-erlangen.de/services/3d.html. Send your structure file (MDL MOLFILE format recommended) to corina@EROS.CCC.Uni-Erlangen.de with a subject line reading Props=A_XYZ ReturnFormat=xxx where xxx is the desired return format (the input format is recognized automatically). Return formats are "mol" - MDL MOLFILE, "xyz" - XYZ format, "pdb" - PDB format, "smd" - Standard Molecular Data, "jcamp" - a spectrosopy standard, "compass", "ctx", "molgen", "sharc", "cascii", and "cbin". The mail body is your structure file without any annotations. Possible input formats are all of the above plus SMILES strings and "441". ------------------------------------------------------------------------------ | Dr. Jens Sadowski | | | | Computer-Chemie-Centrum Tel.: +49 (0)9131 85-6569 | | Universitaet Erlangen-Nuernberg FAX: +49 (0)9131 85-6566 | | Naegelsbachstrasse 25 Email: Sadowski@EROS.CCC.Uni-Erlangen.DE | | D-91052 Erlangen, Germany | ------------------------------------------------------------------------------ From owner-chemistry@ccl.net Wed Jun 28 08:52:36 1995 Received: from mailhub.cc.columbia.edu for shenkin@still3.chem.columbia.edu by www.ccl.net (8.6.10/930601.1506) id IAA07517; Wed, 28 Jun 1995 08:39:21 -0400 Received: from still3.chem.columbia.edu by mailhub.cc.columbia.edu with SMTP id AA19921 (5.65c+CU/IDA-1.4.4/HLK for <@mailhub.cc.columbia.edu:chemistry@ccl.net>); Wed, 28 Jun 1995 08:39:08 -0400 Received: by still3.chem.columbia.edu (931110.SGI/930416.SGI.AUTO) for @mailhub.cc.columbia.edu:chemistry@ccl.net id AA07146; Wed, 28 Jun 95 08:39:07 -0400 From: "Peter Shenkin" Message-Id: <9506280839.ZM7144@still3.chem.columbia.edu> Date: Wed, 28 Jun 1995 08:39:05 -0400 In-Reply-To: "CCL:MacroModel w/ Linux OS?" (Jun 28, 1:15pm) References: <9506281115.AA44597@rzurs3.unizh.ch> X-Mailer: Z-Mail (3.1.0 22feb94 MediaMail) To: , chemistry@ccl.net Subject: Re: CCL:MacroModel w/ Linux OS? Content-Type: text/plain; charset=us-ascii Mime-Version: 1.0 On Jun 28, 1:15pm, wrote: > Subject: CCL:MacroModel w/ Linux OS? > If anyone has succeeded in getting the programme MacroModel to run under > the Linux operating system, I would be most grateful if you would contact me. We do not support or license this configuration, so if anybody has succeeded in this, I would be most grateful if he would contact me as well. :-) > Thanks in advance for your cooperation. Ditto. -P. -- ************************ The secret of life: ************************* *Peter S. Shenkin, Box 768 Havemeyer Hall, Chemistry, Columbia Univ.,* *NY, NY 10027; shenkin@columbia.edu; (212)854-5143; FAX: 678-9039* ************* If you find a loose thread, don't pull it. ************* From owner-chemistry@ccl.net Wed Jun 28 09:07:35 1995 Received: from ohstpw.mps.ohio-state.edu for L330%SUEARN2.BITNET@mps.ohio-state.edu by www.ccl.net (8.6.10/930601.1506) id JAA07923; Wed, 28 Jun 1995 09:06:05 -0400 From: Received: from SUEARN2.BITNET (MAILER@SUEARN2) by MPS.OHIO-STATE.EDU (PMDF V5.0-3 #9122) id <01HS8FOWWB808WWTPN@MPS.OHIO-STATE.EDU> for CHEMISTRY@ccl.net; Wed, 28 Jun 1995 09:06:04 -0400 (EDT) Date: Mon, 19 Jun 95 19:09 MSK Subject: newest DEC computers for quantum chemistry: test 178 of G92/G94 To: CHEMISTRY@ccl.net Message-id: <01HS8FOX028Y8WWTPN@MPS.OHIO-STATE.EDU> Content-transfer-encoding: 7BIT Dear CCLers ! Do somebody have the times for test 178 of G92/G94 running on new DEC computers 8200/8400 or at least on DEC2100 5/250 (both are based on the newest 21164 chip) ? It's interesting to compare this data for comparison of performance of SGI Power Challenge and DEC 8200/8400 for quantum-chemical tasks. Best regards, Dr. N. Anikin, N.D.Zelinsky Institute of Organic Chemistry, Moscow From owner-chemistry@ccl.net Wed Jun 28 09:13:28 1995 Received: from ohstpw.mps.ohio-state.edu for L330%SUEARN2.BITNET@mps.ohio-state.edu by www.ccl.net (8.6.10/930601.1506) id JAA07837; Wed, 28 Jun 1995 09:02:06 -0400 From: Received: from SUEARN2.BITNET (MAILER@SUEARN2) by MPS.OHIO-STATE.EDU (PMDF V5.0-3 #9122) id <01HS8FJZBS1S8WWTQV@MPS.OHIO-STATE.EDU> for CHEMISTRY@ccl.net; Wed, 28 Jun 1995 09:02:05 -0400 (EDT) Date: Wed, 21 Jun 95 18:52 MSK Subject: newest DEC computers for quantum chemistry:TEST 178 for g92/g94 To: CHEMISTRY@ccl.net Message-id: <01HS8FJZF9FM8WWTQV@MPS.OHIO-STATE.EDU> Content-transfer-encoding: 7BIT Dear CCLers ! Do somebody have the times for test 178 of G92/G94 running on new DEC computers 8200/8400 or at least on DEC2100 5/250 (both are based on the newest 21164 chip) ? It's interesting to compare this data for comparison of performance of SGI Power Challenge and DEC 8200/8400 for quantum-shemical tasks. Best regards, Dr. N. Anikin, N.D.Zelinsky Institute of Organic Chemistry, Moscow From owner-chemistry@ccl.net Wed Jun 28 10:22:34 1995 Received: from ns.trans.net for kmay@trans.net by www.ccl.net (8.6.10/930601.1506) id KAA10213; Wed, 28 Jun 1995 10:22:08 -0400 Received: from [194.59.178.14] by ns.trans.net (4.1/SMI-4.1) id AA09275; Wed, 28 Jun 95 16:21:59 BST Message-Id: <9506281521.AA09275@ns.trans.net> X-Sender: kmay@mailhost (Unverified) Mime-Version: 1.0 Content-Type: text/plain; charset="us-ascii" Date: Wed, 28 Jun 1995 16:23:29 +0200 To: chemistry@ccl.net From: kmay@trans.net (Klaus J.W.May) Subject: European FTP Site for SCULPT available Hi Netters: many European Chemists who wanted to download SCULPT via the WWW from http://www.intsim.com/~isigen faced some problems with slow connection speeds and timeouts. Now there is a European FTP site on my server. Since anonymous FTP is not set up on this machine yet, everybody who wants to download SCULPT should please send me a short email and I will reply with all Instructions. SCULPT was developed from Profs. Jane and Dave Richardson at Duke, and Mark Surles at the San Diego Supercomputercenter and is sold now through Interactive Simulations ( Mark@intsim.com) for US$ 700 for Universities and US$ 2.500,- for Industrial Customer. It does interactive realtime minimizations of molecular structures and requires an SGI. Bye Klaus J.W. May e-mail: kmay@trans.net May & Partner SciTech Consult Phone/Fax: xx49-(89) 333 569 Mandlstr. 15 Mobile national: 0172-620 38 38 international: xx49-172-620 30 38 D - 80802 Munich GERMANY From owner-chemistry@ccl.net Wed Jun 28 11:10:10 1995 Received: from shiva.jussieu.fr for bouyer@ext.jussieu.fr by www.ccl.net (8.6.10/930601.1506) id LAA11279; Wed, 28 Jun 1995 11:00:02 -0400 Received: from idf.ext.jussieu.fr (idf.ext.jussieu.fr [134.157.81.129]) by shiva.jussieu.fr (8.6.10/jtpda-5.1) with ESMTP id QAA20804 for ; Wed, 28 Jun 1995 16:59:53 +0200 Received: from [134.157.11.12] by idf.ext.jussieu.fr (8.6.10/jtpda-4.0) with SMTP; Wed, 28 Jun 1995 16:59:50 +0200 X-Sender: bouyer@idf.ext.jussieu.fr Message-Id: Mime-Version: 1.0 Content-Type: text/plain; charset="us-ascii" Date: Wed, 28 Jun 1995 17:04:12 +0100 To: chemistry@ccl.net From: bouyer@ext.jussieu.fr (Frederic BOUYER) Subject: Summary: Gamess - Trudge keyword Hello, I'll sum up replies about the TRUDGE keyword in Gamess. Special thanks are due to Dr. David Heisterberg and Dr. Brett Bode for our fruitful discussions. ============================================================================== >From Dr. Brett Bode: Hello, The trudge keyword activates a Direct Energy minimization mechanism for optimizing geometries. What this means is the GAMESS takes many small steps along each degree of freedom for the geometry and then chooses the one resulting in the lowest energy. This method requires many more geometry points to find a minimum, but it does not require analytic energy derivatives, and thus can be used when the analytic derivatives are unavailable (as is the case for MP2 in GAMESS) or when the analytic derivative requires to much disk or memory. I should stress that the Trudge method is very expensive in terms of CPU time. In fact it is probably only realistic to optimize 2-5 degrees of freedom with this method (freezing the others). But it is the only way to do MP2 optimizations in GAMESS at the moment. Several other codes do allow MP2 gradients such as Gaussian and others... Brett ============================================================================== >From Dr. David Heisterberg: TRUDGE is a non-gradient method. It's limited to optimizing 10 parameters, so it can only work for small molecules. But then it's very slow so you wouldn't want to use it for anything large. It is the only method for MP2 and CI for which analytical gradients are not available. It's really not recommended for geometry optimization. Rather, it's better suited for optimizing exponents for a contracted basis. Dave Heisterberg ============================================================================== >From Will McCarthy: >From: bouyer@ext.jussieu.fr (Frederic BOUYER) >Dear Netters, >I was wondering what the keyword TRUDGE (optmiz=geometry) precisely means >in Gamess, and how this optimizer works for obtaining a structure at the >HF/MP2 level. >Is it the only way to optimize a structure at the MP2 level? I'm not personally familiar with the GAMESS program package, but the TRUDGE keyword most probably refers to a Powell-Fletcher type algorithm to be employed for geometry optimization. This algorithm adjusts each parameter (i.e. internal coordinate for a geometry optimization) individually, then repeats the procedure until self-consistent. The advantage is that there is no need for the gradient, or hessian. However, it is very slow. Good luck, Will McCarthy ============================================================================== >From Patrick Bultinck: On Wed, 21 Jun 1995, Frederic BOUYER wrote: > Dear Netters, > > I was wondering what the keyword TRUDGE (optmiz=geometry) precisely means > in Gamess, and how this optimizer works for obtaining a structure at the > HF/MP2 level. > Have a look at REFS.DOC, I believe it is described there. > Is it the only way to optimize a structure at the MP2 level? It is. The number of parameters that can be optimized at the same time is restricted to 10 ! > > Thank you for responding. > > Frederic Bouyer > Lab. Electrochimie et Chimie Analytique, Paris - France > bouyer@ext.jussieu.fr > http://alcyone.enscp.jussieu.fr/Pages/LECA/GP/FB/ > > > Patrick University of Ghent, Belgium =============================================================================== ************************************************************* * Frederic Bouyer * * Lab. Electrochimie et Chimie Analytique, Paris - France * * bouyer@ext.jussieu.fr * * http://alcyone.enscp.jussieu.fr/Pages/LECA/GP/FB/ * ************************************************************* From owner-chemistry@ccl.net Wed Jun 28 11:37:39 1995 Received: from sprintf.merit.edu for Karl.F.Moschner@urlus.sprint.com by www.ccl.net (8.6.10/930601.1506) id LAA12130; Wed, 28 Jun 1995 11:33:46 -0400 From: X400-Received: by /PRMD=LANGATE/ADMD=TELEMAIL/C=GB/; Relayed; Wed, 28 Jun 1995 10:03:00 -0400 X400-Received: by /PRMD=LANGATE/ADMD=TELEMAIL/C=GB/; Relayed; Wed, 28 Jun 1995 10:03:00 -0400 X400-Received: by /PRMD=LANGATE/ADMD=TELEMAIL/C=GB/; Relayed; Wed, 28 Jun 1995 10:03:00 -0400 X400-Received: by /PRMD=LANGATE/ADMD=TELEMAIL/C=GB/; Relayed; Wed, 28 Jun 1995 10:03:00 -0400 Date: Wed, 28 Jun 1995 10:03:00 -0400 X400-Originator: Karl.F.Moschner@urlus.sprint.com X400-Recipients: non-disclosure:; X400-MTS-Identifier: [/PRMD=LANGATE/ADMD=TELEMAIL/C=GB/;Wed Jun 28 10:03:00 199500] X400-Content-Type: P2-1984 (2) Content-Identifier: Re: CCL:CoMFA pa Message-ID: <"Wed Jun 28 10:03:00 199500*/I=F/G=Karl/S=Moschner/OU=4267EDUR/O=TMUS.URL/PRMD=LANGATE/ADMD=TELEMAIL/C=GB/"@MHS> To: chemistry@ccl.net, j.nilsson@farm.rug.nl Subject: Re: CCL:CoMFA patent? Dear Netters, > In the summary from Michael Dooley, Wayne Steinmetz claims that there is a > patent for CoMFA as a method. What exactly stands in this patent? > If there is such a patent, where can I get a copy of the official > patent documents? I recall that a US patent on CoMFA by Tripos Associates, St. Louis, MO, issued about 3 years ago. Try contacting your local representative. A copy of the US patent may be had from several sources including the US Patent office. Check with your library. It was also abstracted in Chemical Abstracts. Sorry, I don't have the patent number handy but maybe someone from Tripos will see this and respond. Karl _______________________________________________________________________ / \ | Comments are those of the author and not Unilever Research U. S. | | | | Karl F. Moschner, Ph. D. | | | | Unilever Research U. S. e-mail: Karl.F.Moschner@urlus.sprint.com | | 45 River Road Phone: (201) 943-7100 x2629 | | Edgewater, NJ 07020 FAX: (201) 943-5653 | \_______________________________________________________________________/ From owner-chemistry@ccl.net Wed Jun 28 12:22:35 1995 Received: from CHEMVAX.PRINCETON.EDU for debm@CHEMVAX.PRINCETON.EDU by www.ccl.net (8.6.10/930601.1506) id MAA13010; Wed, 28 Jun 1995 12:10:07 -0400 From: Received: by CHEMVAX.PRINCETON.EDU (MX V3.3 VAX) id 13792; Wed, 28 Jun 1995 12:09:13 EDT Date: Wed, 28 Jun 1995 12:09:08 EDT To: chemistry@ccl.net CC: debm@CHEMVAX.PRINCETON.EDU Message-ID: <009928D8.6F71B420.13792@CHEMVAX.PRINCETON.EDU> Subject: use of MESSAGE keyword to modify nuclear charge in GAUSSIAN-92 HI I want to run Gaussian-92 for a cluster (say of 3 diatomic molecules) with specified geometry and basis. I want the charge distribution to be modified so that each molecule of the cluster become neutral. I learnt that MESSAGE keyword allows one to modify nuclear charges on desired centers. But I am not being able to use the MESSAGE keyword. If anyone can help me with an example INPUT, I would appreciate very much. Please send mails to 'debm@chemvax.princeton.edu' Thanks From owner-chemistry@ccl.net Wed Jun 28 12:28:51 1995 Received: from sprintf.merit.edu for Karl.F.Moschner@urlus.sprint.com by www.ccl.net (8.6.10/930601.1506) id MAA13144; Wed, 28 Jun 1995 12:17:50 -0400 From: X400-Received: by /PRMD=LANGATE/ADMD=TELEMAIL/C=GB/; Relayed; Wed, 28 Jun 1995 11:02:00 -0400 X400-Received: by /PRMD=LANGATE/ADMD=TELEMAIL/C=GB/; Relayed; Wed, 28 Jun 1995 11:02:00 -0400 X400-Received: by /PRMD=LANGATE/ADMD=TELEMAIL/C=GB/; Relayed; Wed, 28 Jun 1995 11:02:00 -0400 X400-Received: by /PRMD=LANGATE/ADMD=TELEMAIL/C=GB/; Relayed; Wed, 28 Jun 1995 11:02:00 -0400 Date: Wed, 28 Jun 1995 11:02:00 -0400 X400-Originator: Karl.F.Moschner@urlus.sprint.com X400-Recipients: non-disclosure:; X400-MTS-Identifier: [/PRMD=LANGATE/ADMD=TELEMAIL/C=GB/;Wed Jun 28 11:02:24 199502] X400-Content-Type: P2-1984 (2) Content-Identifier: Re: NMR Analysis Message-ID: <"Wed Jun 28 11:02:24 199502*/I=F/G=Karl/S=Moschner/OU=4267EDUR/O=TMUS.URL/PRMD=LANGATE/ADMD=TELEMAIL/C=GB/"@MHS> To: chemistry@ccl.net, 71552.1635@compuserve.com Subject: Re: NMR Analysis for Macs > We need desperately an application for processing data from a Bruker NRM > spectrometer. We have Macs and IBM PC's but no workstation. Our WinNMR is > to expensive and I know that third party products are available at lower > prices. I appreciate any comments for infos regarding appropriate > software. In 1992 I looked at MacFID. It was a very nice product which worked with various vendors systems/files. Unfortunately we had to give up our Macs. I don't know if they are still in business but the last information I have is: MacFID by TecMag, inc. 6006 Bellaire Blvd. Houston, TX 77081 Sorry, no phone number. Good luck. Karl _______________________________________________________________________ / \ | Comments are those of the author and not Unilever Research U. S. | | | | Karl F. Moschner, Ph. D. | | | | Unilever Research U. S. e-mail: Karl.F.Moschner@urlus.sprint.com | | 45 River Road Phone: (201) 943-7100 x2629 | | Edgewater, NJ 07020 FAX: (201) 943-5653 | \_______________________________________________________________________/ From owner-chemistry@ccl.net Wed Jun 28 12:37:38 1995 Received: from crash.cts.com for surles@intsim.com by www.ccl.net (8.6.10/930601.1506) id MAA13288; Wed, 28 Jun 1995 12:28:41 -0400 Received: from [198.68.169.77] by crash.cts.com with smtp (Smail3.1.28.1 #23) id m0sQzyB-0000HZC; Wed, 28 Jun 95 09:28 PDT Message-Id: X-Sender: surles@crash.cts.com Mime-Version: 1.0 Content-Type: text/plain; charset="us-ascii" Date: Wed, 28 Jun 1995 09:30:50 -0800 To: chemistry@ccl.net From: surles@intsim.com (Mark C. Surles) Subject: Molecular SCULPTing Software available Interactive Simulations, Inc. released SCULPT to the World Wide Web. SCULPT is the first system that allows interactive manipulation of molecular structures while computing molecular mechanics in real time. SCULPT now lets one use a mouse to grab onto atoms, secondary structures, and ligands and literally move them around while other atoms move due to the changed atom positions. SCULPT is the culmination of ten man years of effort by Dr. Mark Surles, Profs. David and Jane Richardson, and Prof. Fred Brooks. SCULPT works with, and increases the functionality of, other modeling systems. The interface takes only minutes to learn. SCULPT is an ideal complement to many areas of molecular modeling including: Homology--interactively move loops, splice points, and sidechains; Membrane proteins--interactively move secondary structure; Ligand & receptors--interactively dock ligands into flexible receptors. Download a fully functional trial with demo data sets by using Netscape/Mosaic (URL: http://www.intsim.com/~isigen), or email us at intsim-support@intsim.com. July's pricing: $700 (academic) and $2500 (commercial). Mark Surles surles@intsim.com Interactive Simulations, Inc. Phone: (619) 658-9462 5330 Carroll Canyon Road FAX: (619) 658-9463 Suite 203 Email: surles@intsim.com San Diego, CA 92121 URL: http://www.intsim.com/~isigen From owner-chemistry@ccl.net Wed Jun 28 13:22:36 1995 Received: from srv.cip.physik.tu-muenchen.de for thuber@Physik.TU-Muenchen.DE by www.ccl.net (8.6.10/930601.1506) id NAA14287; Wed, 28 Jun 1995 13:14:26 -0400 Received: from ss0.cip.physik.tu-muenchen.de by srv.cip.physik.tu-muenchen.de with SMTP id AA09500 for (5.67a/IDA-1.5/bs04); Wed, 28 Jun 1995 19:14:21 +0200 Received: by ss0.cip.physik.tu-muenchen.de (4.1/SMI-4.1) id AA26581; Wed, 28 Jun 95 19:14:20 +0200 Date: Wed, 28 Jun 95 19:14:20 +0200 From: Thomas.Huber@Physik.TU-Muenchen.DE Message-Id: <9506281714.AA26581@ss0.cip.physik.tu-muenchen.de> To: chemistry@ccl.net Subject: GAMESS problems on large data set Hi Netters! Using the (parallel) IBM SP2 version of GAMESS with a large atomic system (a lipid with 130 atoms), control cards: $CONTRL SCFTYP=RHF RUNTYP=ENERGY COORD=CART $END $SYSTEM TIMLIM=999999 MEMORY=3000000 $END $BASIS GBASIS=N21 NGAUSS=3 $END $SCF DIRSCF=.TRUE. $END $DATA lipid C1 ..... cartesian coordinates ..... $END The program stops with this message: ... previous lines skipped .... *** FATAL ERROR *** THE INPUT BASIS SET CONTAINS A LINEAR DEPENDENCE. INPUT BASIS DIMENSION= 614 SALC DIMENSION= 614 THE SMALLEST EIGENVALUE OF THE OVERLAP MATRIX IS .00000000 THERE ARE 48 EIGENVALUES LESS THAN 1.00E-10 THE NUMBER OF LINEARLY INDEPENDENT ORBITALS KEPT IS 566 IF THERE ARE ANY SMALL EIGENVALUES: CHECK YOUR OUTPUT FILE FOR DUPLICATE ATOMIC COORDINATES, OR FOR DUPLICATE BASIS FUNCTIONS, OR FOR ZERO CONTRACTIONS, AND THEN RESUBMIT THIS JOB. IF THE SALC SPACE DOES NOT MATCH THE INPUT BASIS DIMENSION: CHECK TO BE SURE YOU SCRUPULOUSLY FOLLOWED THE CONVENTION FOR AXIS ORIENTATION IN $DATA (ESP. PERPENDICULAR C2 AXES) AND THEN RESUBMIT THIS JOB. EXECUTION OF GAMESS TERMINATED ABNORMALLY AT 10:38:23 CST 28-JUN-1995 ... also last lines skipped ... I got the same message (even the numbers) with a 6-N31 basis set. Any suggestions? What went wrong? Are there any workarounds or bugfixes? (My version is dated 17 NOV 94) Thany you in advance! Thomas Huber Institut fuer Physikalische Biochemie der Universitaet Muenchen Schillerstrasse 44 80336 Muenchen Germany email: thuber@physik.tu-muenchen.de PS: I've tested the version on smaller molecules&std. tests with success. From owner-chemistry@ccl.net Wed Jun 28 13:52:37 1995 Received: from oldspice.pg.com for laidig@pg.com by www.ccl.net (8.6.10/930601.1506) id NAA14827; Wed, 28 Jun 1995 13:43:41 -0400 Received: by oldspice.pg.com (8.6.11/8.6.9) id NAA21468 for <@oldspice.pg.com:chemistry@ccl.net>; Wed, 28 Jun 1995 13:37:57 -0400 id NAA21468; Wed, 28 Jun 1995 13:37:57 -0400 Received: from pandora.pg.com(137.176.2.4) by oldspice.pg.com via smap (V1.3) id sma021466; Wed Jun 28 13:37:38 1995 Received: from morpheus by pandora via SMTP (950215.SGI.8.6.10/930416.SGI.AUTO) for <@pandora.na.pg.com:chemistry@ccl.net> id NAA13794; Wed, 28 Jun 1995 13:44:17 -0400 Received: by morpheus (931110.SGI/930416.SGI.AUTO) for @pandora.na.pg.com:chemistry@ccl.net id AA14299; Wed, 28 Jun 95 13:44:17 -0400 Date: Wed, 28 Jun 95 13:44:17 -0400 From: laidig@pg.com (Bill Laidig) Message-Id: <9506281344.ZM14297@morpheus.na.pg.com> In-Reply-To: "CCL:NMR Analysis for Macs" (Jun 28, 11:02am) References: <"Wed Jun 28 11:02:24 199502*/I=F/G=Karl/S=Moschner/OU=4267EDUR/O=TMUS.URL/PRMD=LANGATE/ADMD=TELEMAIL/C=GB/"@MHS> X-Mailer: Z-Mail (3.1.0 22feb94 MediaMail) To: chemistry@ccl.net Subject: Star Array Pprocessors Cc: laidig@morpheus.na.pg.com Content-Type: text/plain; charset=us-ascii Mime-Version: 1.0 Free to a Good Home The computational chemistry (CADMol) group at P&G is getting rid of 2 Star ST-50 array processors that we used to use for CHARMm calculations. The machines were used as attached processors to an old MicroVAX and come with two Q-bus adaptors. We will donate these to any non-profit institution that wants them. Any costs involved with transfer such as shipping will not be paid by P&G. E-mail or call if interested. Bill -- ****************************************************************************** * "Like jewels in a crown, the precious stones glittered in the queen's * * round metal hat." - Jack Handey * * * * Bill Laidig * * The Procter & Gamble Co. tel 513-627-2857 fax - 1233 * * Miami Valley Laboratories laidig@pg.com (preferred) * * P.O. Box 538707 wd_laidig@pg.com * * Cincinnati, OH 45253-8707 laidig@qtp.ufl.edu * ****************************************************************************** From owner-chemistry@ccl.net Wed Jun 28 14:07:36 1995 Received: from green.CCIT.Arizona.EDU for POLLARD@CCIT.ARIZONA.EDU by www.ccl.net (8.6.10/930601.1506) id NAA15005; Wed, 28 Jun 1995 13:55:33 -0400 From: Received: from CCIT.ARIZONA.EDU by CCIT.ARIZONA.EDU (PMDF V4.3-13 #2381) id <01HS8JEG1TES8ZEJXD@CCIT.ARIZONA.EDU>; Wed, 28 Jun 1995 10:55:18 -0700 (MST) Date: Wed, 28 Jun 1995 10:55:18 -0700 (MST) Subject: cation calcs To: chemistry@ccl.net Message-id: <01HS8JEG2CP28ZEJXD@CCIT.ARIZONA.EDU> X-Envelope-to: chemistry@ccl.net X-VMS-To: IN%"chemistry@ccl.net" MIME-version: 1.0 Content-transfer-encoding: 7BIT I was wondering what people thought about the most viable molecular orbital approach to dealing with finding optimized geometries for +1 cations of organic molecules. I have been just using UHF theory. Are there better theories for dealing with these species? John Pollard From owner-chemistry@ccl.net Wed Jun 28 15:52:41 1995 Received: from laue.biochem.ubc.ca for prabha@laue.biochem.ubc.ca by www.ccl.net (8.6.10/930601.1506) id PAA18017; Wed, 28 Jun 1995 15:50:02 -0400 Received: by laue.biochem.ubc.ca (920330.SGI/920502.SGI.AUTO) for chemistry@ccl.net id AA03340; Wed, 28 Jun 95 12:48:26 -0700 Date: Wed, 28 Jun 1995 12:48:26 -0700 (PDT) From: Prabha Siddarth To: chemistry@ccl.net Subject: CCL: structure of cubane Message-Id: Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII I am having trouble finding coordinates (from a crystal structure study or such) for cubane or some derivative of cubane. I don't have access to Cambridge Structural Database (I am working on that) but meanwhile I was wondering if anybody knows where I can get them from (any references etc)? Or if anybody currently has the coordinates, I would greatly appreciate hearing form them. Thanks Prabha Siddarth From owner-chemistry@ccl.net Wed Jun 28 16:04:26 1995 Received: from cheetah.it.wsu.edu for brian@bert.chem.wsu.edu by www.ccl.net (8.6.10/930601.1506) id PAA17917; Wed, 28 Jun 1995 15:38:18 -0400 Received: from bert.chem.wsu.edu (bert.chem.wsu.edu [134.121.43.22]) by cheetah.it.wsu.edu (8.6.10/WSUit-1.1) with SMTP id MAA09180 for ; Wed, 28 Jun 1995 12:38:06 -0700 Received: by bert.chem.wsu.edu (AIX 3.2/UCB 5.64/4.03) id AA17355; Wed, 28 Jun 1995 12:38:34 -0700 From: brian@bert.chem.wsu.edu (Brian W. Beck) Message-Id: <9506281938.AA17355@bert.chem.wsu.edu> Subject: SCULPT and Chemical Intuition To: chemistry@ccl.net Date: Wed, 28 Jun 1995 12:38:34 -0800 (PDT) X-Mailer: ELM [version 2.4 PL13] Mime-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7bit Content-Length: 1015 Two things I worry about when I hear about programs like SCULPT is : 1) The "real time" molecular mech. calcs. may be slow for reasonably large systems. 2) The interface seems to rely heavily on "chemical intuition" which often can help you overcome problems, but can just as likely lead you down the garden path. (i.e lead you to false interpretations.) -Brian -- ============================================================================= | .---------.| Brian W. Beck | E-mail Addresses: | |/\ | ||--------------------| brian@bert.chem.wsu.edu | || \\ WSU || Biochem/Biophysics | brian_beck@wsu.edu | |\ - *|| WSU , 206 Fulmer | URL http://elmo.chem.wsu.edu/~brian | | | || Pullman, WA | VOICE (509) 335-4083 | | \___________|| 99164-4660 | FAX (509) 335-9688 | ============================================================================= From owner-chemistry@ccl.net Wed Jun 28 21:52:44 1995 Received: from nic.cerf.net for marvin@iris51.biosym.com by www.ccl.net (8.6.10/930601.1506) id VAA22763; Wed, 28 Jun 1995 21:47:12 -0400 Received: from bioc1 (bioc1.biosym.com [146.202.0.2]) by nic.cerf.net (8.6.10/8.6.9) with ESMTP id SAA08230 for <@nic.cerf.net:CHEMISTRY@ccl.net>; Wed, 28 Jun 1995 18:47:12 -0700 Received: from iris51.biosym.com by bioc1 via ESMTP (940816.SGI.8.6.9/930416.SGI) for <@bioc1.biosym.com:CHEMISTRY@ccl.net> id SAA26183; Wed, 28 Jun 1995 18:47:18 -0700 Received: by iris51.biosym.com (940816.SGI.8.6.9/930416.SGI) id SAA13368; Wed, 28 Jun 1995 18:47:04 -0700 Date: Wed, 28 Jun 1995 18:47:04 -0700 From: marvin@biosym.com (Marvin Waldman) Message-Id: <199506290147.SAA13368@iris51.biosym.com> To: CHEMISTRY@ccl.net Subject: RE:POSTED RESPONSES: Quantitative assessment of novel ligand Cc: chris@iris51.biosym.com, agiammon@iris51.biosym.com Dear Netters, On June 28, 1995, Michael Dooley posted a number of responses to his original post about software packages that can predict binding constants: >>I'm searching for a protocol or recipe of 'vital statistics' to assess >>novel ligands that i've designed, so that i'll have firm arguments to >>convince organic chemists to synthesise a molecule. I'm using biosym >>software + intuition to de novo design ligands for a target with good >>x-ray data and also have access to Oxford Molecular software. If it >>might not be possible to roughly predict binding constants for novel >>compounds that differ greatly from known ligands, are there methods to >>predict the effects of modifications to known ligands. I'm aware of >>scoring functions such as Bohm Comput-aided mol des (1994) 243, but I'm >>not sure if this would be appropriate. Eagerly awaiting any suggestions. Among the posted responses was the following message from Dick Cramer: >There are probably over a hundred citations for the use of CoMFA >as a tool for predicting biological activities (conversely I know >of none for BioSym or Oxford Molecular save that of Boehm and >Richards, the developers). If you are involved with known receptor >structures, some of the work by Garland Marshall and his collaborators, >for example in JACS, might be relevant. Sorry I don't have specific >referebnces handy -- > yet another biased developer, Dick Cramer > >cramer@xhost3.tripos.com I would just like to make a minor correction to this posting. In fact, a publication on the application of Hans Boehm's Ludi program to de Novo design problems from an author other than Dr. Boehm or an employee of Biosym appears in the following reference: "Rational Modification of Human Synovial Fluid Phospholipase A2 Inhibitors", M.T. Pisabarro, A.R. Ortiz, A. Palomer, F. Cabre, L. Garcia, R.C. Wade, F. Gago, D. Mauleon, and G. Carganico, J. Med. Chem., Volume 37, pp. 337-341 (1994). In reading the above reference, one finds that Ludi was used to help design "Compound 3 (LM-1228)". Near the end of the article, it is stated that: "Compound 3 (LM-1228) is one of the most potent HSF-PLA2 inhibitors described so far, and represents a new and encouraging lead compound." While there are now many publications and examples of using de Novo design software programs such as Ludi in drug discovery problems, I am not aware of a published application in which the de Novo design program was used by someone other than the original author(s). I would welcome hearing of additional examples that cite usages of de Novo design software from people other than the original developers. Regards, Marvin Waldman, Ph.D. Director, Rational Drug Design Biosym Technologies, Inc. e-mail: marvin@biosym.com From owner-chemistry@ccl.net Wed Jun 28 22:22:44 1995 Received: from sable.nus.sg for cscwyt@leonis.nus.sg by www.ccl.net (8.6.10/930601.1506) id WAA23296; Wed, 28 Jun 1995 22:20:14 -0400 Received: from leonis.nus.sg (cscwyt@leonis.nus.sg [137.132.1.18]) by sable.nus.sg (8.6.10/8.6.9) with ESMTP id KAA09517 for ; Thu, 29 Jun 1995 10:20:10 +0800 Received: (from cscwyt@localhost) by leonis.nus.sg (8.6.10/8.6.9/CNS-3.5) id KAA03612; Thu, 29 Jun 1995 10:20:08 +0800 Date: Thu, 29 Jun 1995 10:20:08 +0800 From: Wong Yat-Ting Message-Id: <199506290220.KAA03612@leonis.nus.sg> To: chemistry@ccl.net Subject: Gaussian 94 on Power Indigo2 Hi Everyone, I have installed Gaussian 94(revision B.1) on a Power Indigo2(OS 6.0.1). I have run all the test jobs that came with the program. For test job 290, I always get a core-dump. Does anyone come across this problem with his/her R8000 ? I would appreciate any suggestions to fix this problem. The following is some information of test job 290 from the output: *************************************** Gaussian 94: SGI-G94RevB.1 16-Apr-1995 14-Jun-1995 *************************************** ---------------------------------------------------------------------- Gaussian Test Job 290 (Part 1): Optimization of the conical Intersecti on 1st job:Optimization for starting orbs. ---------------------------------------------------------------------- Thanks. Yat-Ting Wong cscwyt@nus.sg