From gerwalin@iris1.chemie.uni-kl.de Thu Jul 17 05:07:48 1997 Received: from uni-kl.de for gerwalin@iris1.chemie.uni-kl.de by www.ccl.net (8.8.3/950822.1) id EAA11487; Thu, 17 Jul 1997 04:22:30 -0400 (EDT) Received: from iris1.chemie.uni-kl.de by news.uni-kl.de id aa07015; 17 Jul 97 10:22 MET DST Received: by iris1.chemie.uni-kl.de (940816.SGI.8.6.9/940406.SGI.AUTO) for chemistry@www.ccl.net id KAA07532; Thu, 17 Jul 1997 10:22:24 +0200 Date: Thu, 17 Jul 1997 10:22:24 +0200 From: Elmar Gerwalin Message-Id: <199707170822.KAA07532@iris1.chemie.uni-kl.de> To: chemistry@www.ccl.net Subject: G94 freq iterations SUMMARY(again) (Sorry, but my first summary email was truncated into several single mailfiles, so here's the complete (updated) summary) (I asked : How much steps including the output line "Re-enter D2Numr: IAtom= 1 IXYZ=2 IStep= 1." does a G94 calculation " B3LYP freq=(numer,restart)" (using Cs symmetry) perform ? ) Thanks for all who answered ! Here's the summary (on your request) The "opinions" cover the range from 3N*1 "mostly" to 7N steps. I can't give a correct answer now, just read the following statements that were sent to me. It hasn't become clear (to me) why G94 "mostly" does 6 (or 7) steps for each atom, only 5 steps for atoms lying in the symmetry plane and why my job performs 6 steps for ANY atom, although working in Cs symmetry. I will go on checking that out and perhaps tell you soon! ------ here's the summary ------ 1.) 3N to 6N --From wall@phys.chem.ethz.ch Fri Jul 11 13:49:59 1997 It's easy: N atoms, 3 cartesian coordinates each, 1 step most of the time, 2 steps if g94 finds one is not sufficient. Hence the number of calcs will be somewhere between 3N and 6N. 2.) 6N(+1), decreased by symmetry, 5 or 6 steps per atom For example, in the case of CH2 molecule, Gaussian calculates force constants like next 10 steps. 1 The SCF and gradient calculation at the equilibrium point. 2 Re-enter D2Numr: IAtom= 1 IXYZ=1 IStep= 1. Carbon X axis + direction 3 Re-enter D2Numr: IAtom= 1 IXYZ=2 IStep= 1. Carbon Y axis + direction 4 Re-enter D2Numr: IAtom= 1 IXYZ=3 IStep= 1. Carbon Z axis + direction 5 Re-enter D2Numr: IAtom= 1 IXYZ=3 IStep= 2. Carbon Z axis - direction 6 Re-enter D2Numr: IAtom= 2 IXYZ=1 IStep= 1. hydrogen X axis + direction 7 Re-enter D2Numr: IAtom= 2 IXYZ=2 IStep= 1. hydrogen Y axis + direction 8 Re-enter D2Numr: IAtom= 2 IXYZ=2 IStep= 2. hydrogen Y axis - direction 9 Re-enter D2Numr: IAtom= 2 IXYZ=3 IStep= 1. hydrogen Z axis + direction 10 Re-enter D2Numr: IAtom= 2 IXYZ=3 IStep= 2. hydrogen Z axis - direction The number of steps are 6N+1, (N=number of atom). But, symmetry(for example C2V) can decrease the number to 10(from 19). The skipped 9 steps are, 1 Re-enter D2Numr: IAtom= 1 IXYZ=1 IStep= 2. 2 Re-enter D2Numr: IAtom= 1 IXYZ=2 IStep= 2. 3 Re-enter D2Numr: IAtom= 2 IXYZ=1 IStep= 2. 4 Re-enter D2Numr: IAtom= 3 IXYZ=1 IStep= 1. 5 Re-enter D2Numr: IAtom= 3 IXYZ=1 IStep= 2. 6 Re-enter D2Numr: IAtom= 3 IXYZ=2 IStep= 1. 7 Re-enter D2Numr: IAtom= 3 IXYZ=2 IStep= 2. 8 Re-enter D2Numr: IAtom= 3 IXYZ=3 IStep= 1. 9 Re-enter D2Numr: IAtom= 3 IXYZ=3 IStep= 2. In the case of triatomic molecule XMY(Cs symmetry) is calculated, the required number of steps is 16, 1 The SCF and gradient calculation at the equilibrium point. 2 Re-enter D2Numr: IAtom= 1 IXYZ=1 IStep= 1. 3 Re-enter D2Numr: IAtom= 1 IXYZ=1 IStep= 2. 4 Re-enter D2Numr: IAtom= 1 IXYZ=2 IStep= 1. 5 Re-enter D2Numr: IAtom= 1 IXYZ=2 IStep= 2. 6 Re-enter D2Numr: IAtom= 1 IXYZ=3 IStep= 1. 7 Re-enter D2Numr: IAtom= 2 IXYZ=1 IStep= 1. 8 Re-enter D2Numr: IAtom= 2 IXYZ=1 IStep= 2. 9 Re-enter D2Numr: IAtom= 2 IXYZ=2 IStep= 1. 10 Re-enter D2Numr: IAtom= 2 IXYZ=2 IStep= 2. 11 Re-enter D2Numr: IAtom= 2 IXYZ=3 IStep= 1. 12 Re-enter D2Numr: IAtom= 3 IXYZ=1 IStep= 1. 13 Re-enter D2Numr: IAtom= 3 IXYZ=1 IStep= 2. 14 Re-enter D2Numr: IAtom= 3 IXYZ=2 IStep= 1. 15 Re-enter D2Numr: IAtom= 3 IXYZ=2 IStep= 2. 16 Re-enter D2Numr: IAtom= 3 IXYZ=3 IStep= 1. 3.) 6N, decreased by symmetry, 5 steps for atoms on the symmetry plane, 6 others --From: Carola Begemann Hallo Elmar In C1 Symmetrie( d.h. ohne Symmetrie) fuer jedes Atom im Molekuel 6 Schritte (zwei je Koordinate:x, y, z). (2. Ableitung der Energie nach der Auslenkung) Mit Symmetrie entsprechend weniger. Cs hat eine Spiegelebene, also halb so viel, wenn kein Atom auf der Spiegelebene liegt, fuer jedes Atom in der Spiegelebene nur 5 statt 6 Schritte. ---------------------------------------------- Carola Begemann email: carola@tc1.chemie.uni-bielefeld.de adress: Leuchte 21a, 32657 Lemgo, Germany ---------------------------------------------- --From: frisch@lorentzian.com (Mike Frisch) Without symmetry G94 must do + and - displacements of each of x, y, and z for each atom, plus the energy and gradient at the input geometry, for a total of 6*N+1. Cs symmetry helps in one of two ways: 1) For an atom in the plane of symmetry (say, the xy plane) then displacements above and below the plane (+z and -z) give related contributions (have gradients related by a reflection), so that only one of them need be done and thus 5 points are required. 2) For pairs of atoms related by symmetry (above and below the plane) the displacements of one atoms can be related to the other, so only one atom need be moved. All 6 of its displacements are required. So for Cs symmetry the number of gradient points is 6*I + 5*J + 1, where I is the number of symmetrically related pairs of atoms and J is the number of atoms in the plane (i.e. N=2*I+J is the total number of atoms). The same sort of reasoning applies for higher point groups, with each atom displaced 0, 3, 4, 5 or 6 times depending on whether is is symmetrically related to an earlier atom, at the center of symmetry, on certain axes (e.g., the C2 axis in a C2v molecule), in just a plane of symmetry, or none of the above, respectively. Mike Frisch 4.) 7N --From mbdtsnm@hpf.ch.man.ac.uk Fri Jul 11 14:53:44 1997 --From: "Nathaniel (noj) Malcolm" ... [a very rough rule of thumb would say that (given analytical gradients - and no symmetry) for each atom you will need about 7 gradient calculations - finite differences in 3D] 5.) in general: --From jeffs@xerxes.ccqc.uga.edu Mon Jul 14 21:25:35 1997 I thought you would be inundated with correct answers so I didn't bother answering. You can find this information in any text on numerical analysis of partial differential equations. Basically, if the method has implemented gradients and properly implemented symmetry, you will need two points for each symmetric frequency computation and one for each asymmetric frequency. This assumes that the program does not repeat the calculation of the reference geometry, which you will need. If gradients are not available and the program is calculating frequencies only with energies, you will need at least two points for symmetric frequencies and four points for asymmetric ones. Again, you will also need one point as the reference. All of these numerical approximations are the minimum number of calculations possible with an error of O(h^2). This generally is unacceptable for optimizations, but seems to be the standard for frequency analysis. For further information, see the sections appropriate to numerical approximation of partial derviatives via central difference methods in: Handbook of Mathmatical Functions with Formulas, Graphs, and Mathematical Tables by M. Abramowitz and I. A. Stegun Elementary Numerical Analysis: an algorithmic approach by S.D. Conte and C. de Boor Applied Numerical Methods by B. Carnahan, H. A. Luther, and J.O. Wilkes Applied Numerical Methods with Personal Computers by A. Constantinides Hope I could be of some help. Jeff Jeffrey C. Stephens Center for Computational Quantum Chemistry University of Georgia Athens, GA 30602 (706) 542 - 7732 jeffs@gobryas.ccqc.uga.edu http://zopyros.ccqc.uga.edu/~jeffs/home.html ------ end of this summary ----- If you have further comments, please post them to me or the CCC mailing list. Thanks Bye Elmar ================================================= Elmar Gerwalin , University of Kaiserslautern, Germany Dept. of Theoretical Chemistry (coming soon: http://iris2.chemie.uni-kl.de ) Please send mail to: gerwalin@chemie.uni-kl.de =================================================== From landman@firestorm.physics.wayne.edu Thu Jul 17 09:07:42 1997 Received: from firestorm.physics.wayne.edu for landman@firestorm.physics.wayne.edu by www.ccl.net (8.8.3/950822.1) id IAA12152; Thu, 17 Jul 1997 08:26:51 -0400 (EDT) Received: (from landman@localhost) by firestorm.physics.wayne.edu (950413.SGI.8.6.12/950213.SGI.AUTOCF) id IAA25943; Thu, 17 Jul 1997 08:26:20 -0400 Date: Thu, 17 Jul 1997 08:26:20 -0400 (EDT) From: Joe Landman To: Jeffrey.Nauss@UC.Edu cc: chemistry@www.ccl.net Subject: Re: CCL:Compiling AMBER 4.1 on a Power Challenge In-Reply-To: <9707161606.ZM15724@beryllium.crs.uc.edu> Message-ID: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII y On Wed, 16 Jul 1997, Jeffrey L. Nauss wrote: > I am trying to compile AMBER 4.1 on a Power Challenge. The uname -a output is > "IRIX64 bebop 6.1 07121823 IP21 mips". Specifically, I am trying to get leap > compiled. However the compilation bombs during the command: > > make World >& mkerr & > > The error message at the end of the mkerr file is: > > /usr/bin/cc -o utilMakeHelp -g -DMEMORY_DEBUG=0 -I.. -cckr > -noprototypes -w -Wf,-XNl16386 -xansi -32 -Wf,-XNh2000 basics.o sysdepend.o ^^^^^ > Anybody have a clue what I need to do? I have already tried removing all -32 > options from the Makefile and got the same error. Which compilers are you using? Moreover, if you want an n32 binary producde, make sure you have an -n32 option specified on all of the compiler option and loader option lines. If you want an n64 binary produced, then make sure you have -64 on all of the loader and compiler lines.. email me offline if you have more problems. > > Thanks in advance... > > > -- > Jeffrey L. Nauss, PhD Telephone: 513-556-0148 > Dir. Molec. Model. Serv. Fax: 513-556-9239 > Department of Chemistry e-mail: Jeffrey.Nauss@UC.Edu > University of Cincinnati URL http://www.che.uc.edu/~nauss > > -------This is added Automatically by the Software-------- > -- Original Sender Envelope Address: nauss@beryllium.crs.uc.edu > -- Original Sender From: Address: nauss@beryllium.crs.uc.edu > CHEMISTRY@www.ccl.net: Everybody | CHEMISTRY-REQUEST@www.ccl.net: Coordinator > MAILSERV@www.ccl.net: HELP CHEMISTRY or HELP SEARCH | Gopher: www.ccl.net 73 > Anon. ftp: www.ccl.net | CHEMISTRY-SEARCH@www.ccl.net -- archive search > Web: http://www.ccl.net/chemistry.html > From cdac.ernet.in!gadre@parcom.ernet.in Tue Jul 15 09:07:17 1997 Received: from sangam.ncst.ernet.in for cdac.ernet.in!gadre@parcom.ernet.in by www.ccl.net (8.8.3/950822.1) id IAA29114; Tue, 15 Jul 1997 08:20:59 -0400 (EDT) Received: from iucaa (iucaa.ernet.in [144.16.31.4]) by sangam.ncst.ernet.in (8.7.5) with SMTP id RAA11256 for ; Tue, 15 Jul 1997 17:59:12 +0530 (GMT+05:30) Received: from iucaa.iucaa.ernet.in by iucaa (5.65v3.2/SMI-4.1) id AA17545; Tue, 15 Jul 1997 17:47:51 +0500 Received: by parcom.cdac.ernet.in (4.1/SMI-4.1) id AA27142; Tue Jul 15 17:14:58 1997 (GMT + 0530) Date: Tue Jul 15 17:14:58 1997 (GMT + 0530) From: gadre@cdac.ernet.in Message-Id: <9707151144.AA27142@parcom.cdac.ernet.in> To: CHEMISTRY@www.ccl.net Subject: Int.Conf.Comp. in Chem.Res & Educ. Registr. Deadline Deadline : Registration Fees for ICCCRE Dear Sirs and Madams : The last date of payment of Registration Fees for the conference (US$150 for students and $300 for others) is July 31, 1997. The payment may be made by a Banker's draft drawn on the State Bank of India (DG, Pune) payable to "The Registrar, University of Pune(ICCCRE)". The draft should be mailed to Professor S. R. Gadre Department of Chemistry University of Pune Pune-411007. INDIA. Thanks and looking forward to meet you in Pune in January 1998! Shridhar Gadre, Convenor, XII ICCCRE. For more info see: http://www.ccl.net/cca/info/conferencelist/mess0002.html For further information on Pune University and Pune city, you may visit the web site http://www.unipune.ernet.in http://www.unc.edu/~pune For travel information around Pune you may visit http://iucaa.iucaa.ernet.in/~snk/place1.html http://iucaa.iucaa.ernet.in/~snk/place2.html For travel with in Maharashtra State visit web sites http://spiderman.bu.edu/misc/india/places/indiastates/maharashtra.html http://www.clemson:edu/~nsankar/india/states/maharashtra.html http://wwwvms.utexas.edu/~savkar/rashtra.html From MAILER-DAEMON@www.ccl.net Tue Jul 15 09:07:23 1997 Received: from schiele for MAILER-DAEMON@www.ccl.net by www.ccl.net (8.8.3/950822.1) id IAA29090; Tue, 15 Jul 1997 08:18:03 -0400 (EDT) Received: by schiele (950911.SGI.8.6.12.PATCH825/940406.SGI.AUTO) id OAA09612; Tue, 15 Jul 1997 14:18:28 +0200 From: "Wolf-Dietrich Ihlenfeldt" Message-Id: <9707151418.ZM9610@eros.ccc.uni-erlangen.de> Date: Tue, 15 Jul 1997 14:18:25 -0600 In-Reply-To: Ascanio DiPippo "CCL:Reaction Pathway Program" (Jul 14, 20:15) References: Reply-To: wdi@eros.ccc.uni-erlangen.de X-Phones: +49-9131-85-6579 X-Fax: +49-9131-85-6566 X-Mailer: Z-Mail (3.2.2 10apr95 MediaMail) To: Ascanio DiPippo Subject: Re: CCL:Reaction Pathway Program Cc: CHEMISTRY@www.ccl.net Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 8bit , Joe Golab wrote: > > > Dear CCL Member: > > > > Do you know of any (engineering, chemistry, biological, etc) program that > > given a compound would suggest any and all reaction pathways toward that > > compound (no matter how outlandish from a thermodyanmic standpoint)? > > > > For example, given tolune, the program would suggest: > > > > 1) benzene + methane -> toluene > > 2) methylcyclohexane -> toluene + H2 > > 3) methane + heat/pressure -> toluene + H2 > > 4) ETC. > > > > Perhaps this is really a database that is part of a program. Any leads > > would be gratefully appreciated! Thanks. Programs which perform exhaustive bond reordering for reaction prediction or synthesis planning, or assemble reaction networks between speicified endpoints, can do this. Typically, these programs employ additional constraints to prevent entering the outlandish domains, but these checks can be disabled :-), and thus all reaction pathways generated. Be warned: You quickly generate truly enourmous numbers of pathways. Example programs which could work in this mode are EROS5 (Gasteiger) and IGOR/RAIN (Ugi). For literature references and an overview, see Angewandte Chemie, Int. Ed. 1995, 34, 2613-2633. -- Dr. Wolf-D. Ihlenfeldt Computer Chemistry Center, University of Erlangen-Nuernberg Naegelsbachstrasse 25, D-91052 Erlangen (Germany) Tel (+49)-(0)9131-85-6579 Fax (+49)-(0)9131-85-6566 --- The three proven methods for ultimate success and fame: 1) Nakanu nara koroshite shimae hototogisu 2) Nakanu nara nakasete miseyou hototogisu 3) Nakanu nara naku made matou hototogisu From jtgolab@amoco.com Tue Jul 15 18:07:21 1997 Received: from interlock.amoco.com for jtgolab@amoco.com by www.ccl.net (8.8.3/950822.1) id RAA02300; Tue, 15 Jul 1997 17:52:32 -0400 (EDT) Received: by interlock.amoco.com id AA20799 (InterLock SMTP Gateway 3.0 for CHEMISTRY@www.ccl.net); Tue, 15 Jul 1997 16:52:31 -0500 Message-Id: <199707152152.AA20799@interlock.amoco.com> Received: by interlock.amoco.com (Protected-side Proxy Mail Agent-4); Tue, 15 Jul 1997 16:52:31 -0500 Received: by interlock.amoco.com (Protected-side Proxy Mail Agent-3); Tue, 15 Jul 1997 16:52:31 -0500 Received: by interlock.amoco.com (Protected-side Proxy Mail Agent-2); Tue, 15 Jul 1997 16:52:31 -0500 Received: by interlock.amoco.com (Protected-side Proxy Mail Agent-1); Tue, 15 Jul 1997 16:52:31 -0500 From: jtgolab@amoco.com (Joe Golab) Date: Tue, 15 Jul 1997 16:51:21 -0500 X-Mailer: Z-Mail (3.2.3 08feb96 MediaMail) To: CHEMISTRY@www.ccl.net Subject: SUMMARY - Reaction Pathway Programs Cc: jtgolab@amoco.com Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Hi CCL: Below is the summary of responses to the "retro-synthesis" question I recently asked. Thanks to all who have responded. I have edited some of the answers and so I take full responsibility for any errors. If I get any more answers, I will re-post summary. << Tue Jul 15 16:50:53 CDT 1997 >> Execute Summary of Answers 1) SYNGEN, Jim Hendrickson, Brandeis University 2) CAMEO, Bill Jorgensen, Yale 3) SYNTREE, Commerical Software, Vendor? 4) SYNLIB, Dan Chodosh, may not exist anymore 5) REACCS, MDL 6) CAS's reaction data base 7) Chiron, Steve Hannisan (spl?) of U. of Montreal. 8) LAHSA, E.J. Corey, Harvard U. 9) Unknow, Michael Mavrovouniotis, Northwestern 10) Crossfile, Beilstein :Joe jtgolab@amoco.com (630) 961-7878 ______________________________ Original Note __________________________________ Subject: CCL:Reaction Pathway Program Author: chemistry-request (chemistry-request@www.ccl.net) at unix,sh Date: 7/14/97 4:43 PM Dear CCL Member: Do you know of any (engineering, chemistry, biological, etc) program that given a compound would suggest any and all reaction pathways toward that compound (no matter how outlandish from a thermodyanmic standpoint)? For example, given tolune, the program would suggest: 1) benzene + methane -> toluene 2) methylcyclohexane -> toluene + H2 3) methane + heat/pressure -> toluene + H2 4) ETC. Perhaps this is really a database that is part of a program. Any leads would be gratefully appreciated! Thanks. _____________________________Reply Separator_________________________________ Subject: Re: CCL:Reaction Pathway Program Author: lchen (lchen@mdli.com) at unix,mime Date: 7/14/97 5:16 PM Dear Joe: Please check the following SYNGEN site: http://syngen2.chem.brandeis.edu/syngen.html you may find something interesting you. -Lingran ********************************************************** Lingran Chen, Ph.D. Senior Scientific Programmer MDL Information Systems, Inc. 14600 Catalina Street San Leandro CA 94577 Phone: (510) 895-1313, Ext. 1305 FAX: (510) 614-3616 Email: LCHEN@MDLI.COM URL: http://www.mdli.com http://syngen2.chem.brandeis.edu/~chen/lingran.html ********************************************************** _____________________________Reply Separator_________________________________ Subject: Re: CCL:Reaction Pathway Program Author: eslone (eslone@patriot.net) at unix,mime Date: 7/14/97 6:32 PM Talk to Jim Hendrickson at Brandeis University. He has a program called SynGen. ___________________________________________________________________ J. Eric Slone Scientific Consulting Services 5500 Holmes Run Parkway, Suite 501 Alexandria, Virginia 22304-2851 Phone: (703) 461-7078 mailto:eslone@patriot.net Fax: (703) 751-6639 http://www.patriot.net/users/eslone ___________________________________________________________________ _____________________________Reply Separator_________________________________ Subject: Re: CCL:Reaction Pathway Program Author: dsmith (dsmith@CTCnet.Net) at unix,mime Date: 7/14/97 9:12 PM Joe: I am not familiar with any program that will suggest ALL reaction pathways... there are just way too many possibilities, which is why we still have synthetic organic chemists. You are probably familiar with Bill Jorgensen's CAMEO program (I hope I have the name correct), which can suggest 'reasonable' synthetic routes to various types of compounds and functionality. There is also a commercial program (not that Bill doesn't sell his programs, ;)) called SYNTREE (I believe). There were some papers about this at either the last ACS National meeting in San Francisco or at the Midland, MI, ACS Regional meeting in May. I can look for more information if you wish, but I am at home and just finishing up a vacation while I write this. Regardless, both of these programs use a combination (I believe) of data bases and "expert" algorithms to select likely reactions. I don't know of anything that will give you all possible routes, except perhaps an aggressive undergraduate who has just finished his/her organic final exam. There was also SYNLIB that came from the late Dan Chodosh... I don't know if anyone picked up that program so I can't tell you if it still exists. This was purely data base based and matched based on user-defined descriptors, if I remember correctly from my postdoc days. MDL REACCS and CAS's reaction data base are two others that come to mind. I would also love to hear from anyone else about similar programs. Please post to CCL rather than just to Joe. Doug Smith -- Dr. Douglas A. Smith, President and CEO | voice: (814) 255-7859 The DASGroup, Inc. | fax: (814) 255-3517 1732 Lyter Drive, 2nd Floor | email: dsmith@dasgroup.com Johnstown, PA 15905 | WWW: http://www.dasgroup.com Contract R&D specialists in modeling, simulation, synthesis and risk assessment for chemistry, materials science, and biotechnology. _____________________________Reply Separator_________________________________ Subject: Re: CCL:Reaction Pathway Program Author: Willie (Willie@microsimulations.com) at unix,mime Date: 7/15/97 1:12 AM Joe, Two programs that can do retrosynthetic analysis, 1. Chiron, from Prof. Steve Hannisan (wrong spelling?) of U. of Montreal. 2. LAHSA, from prof. E.J. Corey of Harvard U. -- Willie Cui, Ph.D. voice 201-512-0486 MicroSimulations fax: 201-512-0489 478 Green Mountain Rd. email: willie@microsimulations.com Mahwah, NJ 07430 URL: http://www.microsimulations.com _____________________________Reply Separator_________________________________ Subject: RE: Reaction Pathway Program Author: RICHEYFA (RICHEYFA@ucarb.com) at unix,mime Date: 7/15/97 6:12 AM Hi, Joe, I had a similar question when looking for new routes to commodity chemicals. I found references to techniques for making expensive [usually pharmaceutical] chemicals which would take a target structure and elaborate[!] multistep pathways from known precursors. I think one was E.J. Corey's group's product. At least one of these gave synthetically viable guesses for transformations so probably weeded out a lot of the thermodynamically infeasible routes. I haven't pursued this very far but was left with the feeling that there was a lot of work in the 80's and the only thing that has survived outside academe has been the pharmaceutical part. I may be wrong in this. I never did summarize my work but if you are interested I can send you references with brief comments. I wanted this approach to automate the cataloging of possible synthetic routes including finding the ones that I'd overlook because of my particular chemical background. Forrest Richey Union Carbide Corporation Technical Center Bldg 740 Room 4107 S. Charleston, WV 25303 (304)747-4964 Two things happen when you reach fifty, and if I could remember one, I wouldn't worry about the other two. _____________________________Reply Separator_________________________________ Subject: Reaction Pathways Author: burkhart (burkhart@goodyear.com) at unix,mime Date: 7/15/97 9:00 AM Hi Joe, If I'm not mistaken, Prof. Bill Jorgensen's group @Yale worked on a program called CAMEO. As I remember it, they were trying to use it as a reaction chemistry "assistant"--but I'm not sure how far they got. ----------------------------------+------------------------------------ Papernet: Craig W. Burkhart | Baseball & summer--What could be Goodyear Research | better? The birds are singing and 142 Goodyear Blvd. | the BATS are out! Akron, OH 44305 | Indians update: 48-37 (.564) Mouthnet: 330.796.3163 | 'Best little .500 club' $60 mil Faxnet: .3304 | can buy... (swampland, anyone?) Internet: cburkhart@goodyear.com | Pitching REALLY Stinks!!! UGH! ----------------------------------+------------------------------------ _____________________________Reply Separator_________________________________ Subject: Re: CCL-Reaction Pathway Pro Author: mnliebman (mnliebman@vysis.com) at unix,sh Date: 7/15/97 9:59 AM RE>CCL:Reaction Pathway Program 7/15/97 Joe try contactine Michael Mavrovouniotis at Northwestern- mlmavro@nwu.edu I think Michael 271 7190 _____________________________Reply Separator_________________________________ Subject: Your e-mail to CCL Author: pierre (pierre@mdli.com) at unix,mime Date: 7/15/97 10:14 AM Dear Joe, I received a copy of your e-mail attached at the end of my reply. You may remember that we talked on the phone a few month ago. Although my answer is obviously biased by the fact that I work for MDL, my experience after 9 years working with the large pharma and chemical industries in Europe and in the US is that there seems to be no good way to have a prediction program. A lot of companies have tried, and they have ended up licensing our databases or other (like Beilstein Crossfire). The advantage they have found in our system, compared to other database systems, (especially since we introduced ISIS, the client server system we provide now) is the flexibility of our querying interface. You can search not only on exact reactions, but also on things like " find an example of a reaction where this fragment is formed". Or "find an example of a reaction using these conditions where a fragment is unaltered". As an example, to address your query below, we would draw the toluene, and define it as a product, and then we would perform a search known as "structure as product not as reactant, or "sub-structure as product, not as reactant". Which basically defines that the toluene has to be formed during the reaction. You could also refine the query by specifying certain classes of reactions you do not want (list catalysts that are expensive etc). Running the query you use as an example on our databases leaded to 113 reactions out of 107 publications. The query was exclusively dealing with the toluene as product, no substituted toluene was allowed. In some of these reactions the benzene is a by product, and probably a lot of them are dealing with cleavage from a larger structure, but these reactions could still be of interest, you would have to judge. >> [Parts of Original Message Edited/Deleted] << Sincerely Pierre Allemand Ph.D. Senior Account Manager >-- END -- :Joe jtgolab@amoco.com (630) 961-7878 +---------------------------------------------------------+ | You can pick your friends but you can't pick your nose. | +---------------------------------------------------------+ From MAILER-DAEMON@www.ccl.net Tue Jul 15 19:07:21 1997 Received: from schiele for MAILER-DAEMON@www.ccl.net by www.ccl.net (8.8.3/950822.1) id SAA03163; Tue, 15 Jul 1997 18:59:58 -0400 (EDT) Received: by schiele (950911.SGI.8.6.12.PATCH825/940406.SGI.AUTO) id BAA19483; Wed, 16 Jul 1997 01:00:15 +0200 From: "Wolf-Dietrich Ihlenfeldt" Message-Id: <9707160100.ZM19481@eros.ccc.uni-erlangen.de> Date: Wed, 16 Jul 1997 01:00:11 -0600 In-Reply-To: Richard Bone "CCL:SMILES Database?" (Jul 11, 14:39) References: <199707111412.OAA28712@petersgate.proteus.co.uk> Reply-To: wdi@eros.ccc.uni-erlangen.de X-Phones: +49-9131-85-6579 X-Fax: +49-9131-85-6566 X-Mailer: Z-Mail (3.2.2 10apr95 MediaMail) To: Richard Bone Subject: Re: CCL:SMILES Database? Cc: CHEMISTRY@www.ccl.net Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 8bit On Jul 11, 14:39, Richard Bone wrote: > Subject: CCL:SMILES Database? > > Does anyone know of a public-domain database of SMILES strings for commonly- > occurring small organic molecules and functional groups? I'm looking for > something containing several hundred or more species. > > It would need to be something in ASCII format, for general utility, i.e., not > in a format specific to some commercial package. > > Richard Bone > Well, I made you one in a few minutes. You find it at ftp://schiele.organik.uni-erlangen.de/pub/nci/nci4000.smi.gz It is small, just 45K. These are the first 4000 entries from the NCI database which do not contain a metal atom (just to keep the structures simple). Because the original file does not contain stereochemical information, the SMILES strings do not have any either. Behind the SMILES string, separated by a tab, the corresponding CAS number is appended. Most SMILES readers will understand that only the first word is the string and ignore the second part or even assign it to a name property. At the same site you will find the full original NCI database as SD file, and the same structures in another file with added 3D coordinates. The full database contains about 126.705 structures and is public domain. Since we just has on the CCL a discussion about using scripting languages to control modular programs, here is the short CACTVS Tcl script used to produce this file: set outhandle [molfile open "|gzip >nci4000.smi.gz" w \ format smiles \ hydrogens add \ writeflags {writearo writename}] set cnt 0 molfile loop ftp://schiele/pub/nci/nciopen.mol.gz enshandle { if {![lempty [ens atoms $enshandle metal]]} continue ens assign $enshandle E_*CAS_RN* E_NAME molfile write $outhandle $enshandle if {[incr cnt]>=4000} break } BTW, beware if you want to repeat this with the popular Babel conversion program (V1.6). First, the program will not be able to read the original datafile because it contains neither display coordinates nor 3D coordinates, only connectivity. Babel will report a cryptic message 'No atoms found in this structure', although the file is syntactically correct. You must use the 3D-enhanced file. Second, from the first 1000 records the CACTVS results and Babel results are structurally different for 69 records (7%). As far as I have checked, this is all because the MDL read routines of Babel do not read the atomic charge field in the SD file. This is of course deadly when reading back the SMILES string without charge information, since the SMILES standard contains hydrogen addition rules. So a nitro group which was coded with a positively charged N and a negatively charged O will suddenly contain an N-O-H group because the SMILES string N(=O)O without charge information demands the addition of a hydrogen atom to the single-bonded oxygen. The N will also receive an extra hydrogen, or end up as a radical, depending on your reader software. -- Dr. Wolf-D. Ihlenfeldt Computer Chemistry Center, University of Erlangen-Nuernberg Naegelsbachstrasse 25, D-91052 Erlangen (Germany) Tel (+49)-(0)9131-85-6579 Fax (+49)-(0)9131-85-6566 --- The three proven methods for ultimate success and fame: 1) Nakanu nara koroshite shimae hototogisu 2) Nakanu nara nakasete miseyou hototogisu 3) Nakanu nara naku made matou hototogisu From jfm@mi.leeds.ac.uk Wed Jul 16 06:07:26 1997 Received: from gps1.leeds.ac.uk for jfm@mi.leeds.ac.uk by www.ccl.net (8.8.3/950822.1) id FAA06247; Wed, 16 Jul 1997 05:09:57 -0400 (EDT) Received: from mi.leeds.ac.uk (misun1.leeds.ac.uk [129.11.12.4]) by gps1.leeds.ac.uk (8.8.5/8.8.5) with SMTP id KAA22616; Wed, 16 Jul 1997 10:09:54 +0100 (BST) Sender: jfm@mi.leeds.ac.uk Message-Id: <33CC8FE1.1CFB@mi.leeds.ac.uk> Date: Wed, 16 Jul 1997 10:09:53 +0100 From: Jean-Francois Marchaland X-Mailer: Mozilla 3.01Gold (X11; I; IRIX 5.3 IP22) Mime-Version: 1.0 To: "Douglas A. Smith Ph.D." Cc: CHEMISTRY@www.ccl.net Subject: Re:CCL: Reaction Pathway Program References: <3.0.1.32.19970714221226.009b8fc0@pop.dasgroup.com> Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit Douglas, > > Joe: > > I am not familiar with any program that will suggest ALL reaction > pathways... there are just way too many possibilities, which is why we > still have synthetic organic chemists. > > You are probably familiar with Bill Jorgensen's CAMEO program (I hope I > have the name correct), which can suggest 'reasonable' synthetic routes to > various types of compounds and functionality. Pure and Appl. Chem. vol.62, 10, pp 1921 "Abstract- An interactive computer program, CAMEO, has been developed to predict products of organic reactions given the starting materials and conditions...." At the beginning CAMEO was a reaction simulator, but is there a new module now in CAMEO that " can suggest 'reasonable' synthetic routes to various types of compounds and functionality"? > There is also a commercial > program (not that Bill doesn't sell his programs, ;)) called SYNTREE (I > believe). There were some papers about this at either the last ACS > National meeting in San Francisco or at the Midland, MI, ACS Regional > meeting in May. I can look for more information if you wish, but I am at > home and just finishing up a vacation while I write this. > > Regardless, both of these programs use a combination (I believe) of data > bases and "expert" algorithms to select likely reactions. I don't know of > anything that will give you all possible routes, except perhaps an > aggressive undergraduate who has just finished his/her organic final exam. > > There was also SYNLIB that came from the late Dan Chodosh... I don't know > if anyone picked up that program so I can't tell you if it still exists. > This was purely data base based and matched based on user-defined > descriptors, if I remember correctly from my postdoc days. MDL REACCS and > CAS's reaction data base are two others that come to mind. > > I would also love to hear from anyone else about similar programs. Please > post to CCL rather than just to Joe. > I don't know if they are all maintained and commercialized but a lots of Computer Assisted Organic Synthesis (CAOS) programs that works in a retrosynthetic way have been designed. I suggest you to have a look at: "Computer-assisted Solution of Chemical Problems - The historical Development and the Present State of the Art of a New discipline of Chemistry" by Ivar Ugi and al. in Angew. Chem. Int. Ed. Engl. 1993, 32, 201-227 It's a huge review on computer chemistry, but a good part of it deals with CAOS. Now if you want a quick answer on one of the commercial products, try http://www.chem.leeds.ac.uk/LUK/ Hope it helps Jean-Francois Marchaland _/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/ _/ Dr J.F. Marchaland jfm@mi.leeds.ac.uk _/ _/ ICAMS, School of Chemistry UK: 0113 233 6567 _/ _/ University of Leeds internat.: +44 113 233 6567 _/ _/ LS29JT LEEDS FAX: 6563 _/ _/ _/ _/ http://chem.leeds.ac.uk/ICAMS/people/jfm.html _/ _/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/ From mclark@smtpgwy.isinet.com Wed Jul 16 09:22:29 1997 Received: from isinet.com for mclark@smtpgwy.isinet.com by www.ccl.net (8.8.3/950822.1) id IAA06882; Wed, 16 Jul 1997 08:19:17 -0400 (EDT) From: Received: from smtpgwy.isinet.com ([198.62.99.211]) by pandora.isinet.com with SMTP id <18443>; Wed, 16 Jul 1997 08:21:01 -0400 Received: from ccMail by smtpgwy.isinet.com (SMTPLINK V2.11.01) id AA869066495; Wed, 16 Jul 97 08:16:29 EST Date: Wed, 16 Jul 1997 09:16:29 -0400 Message-Id: <9706168690.AA869066495@smtpgwy.isinet.com> To: wjs@csb0.ipc.pku.edu.cn, wdi@eros.ccc.uni-erlangen.de Cc: chemistry@www.ccl.net Subject: Re: CCL:Re: CCL:Where is software on interconversion of chem There are some software packages for Wiswesser notation. You can contact Fraser-Williams for either the software, or they can convert from the WLN database for you on a consulting basis. ______________________________ Reply Separator _________________________________ Subject: CCL:Re: CCL:Where is software on interconversion of chemical Author: wdi@eros.ccc.uni-erlangen.de at INTERNET Date: 7/15/97 7:56 PM From jerickson@dowelanco.com Wed Jul 16 13:10:23 1997 Received: from elinet1.dowelanco.com for jerickson@dowelanco.com by www.ccl.net (8.8.3/950822.1) id MAA08194; Wed, 16 Jul 1997 12:49:52 -0400 (EDT) Received: by elinet1.dowelanco.com id AA25789 (InterLock SMTP Gateway 3.0 for chemistry@www.ccl.net); Wed, 16 Jul 1997 11:49:48 -0500 Received: by elinet1.dowelanco.com (Internal Mail Agent-1); Wed, 16 Jul 1997 11:49:48 -0500 Message-Id: From: "Erickson, Jon" To: "'Gina Barbeau'" Cc: "'chemistry@www.ccl.net'" Subject: RE: A request for help on molecular modeling simulations. Date: Wed, 16 Jul 1997 11:50:58 -0500 X-Mailer: Microsoft Exchange Server Internet Mail Connector Version 4.0.994.63 Mime-Version: 1.0 Content-Type: text/plain; charset="us-ascii" Content-Transfer-Encoding: 7bit Gina, >---------- >From: Gina Barbeau[SMTP:gbarbeau@eagle.ibc.edu] >Sent: Wednesday, July 16, 1997 10:43 AM >To: chemistry@www.ccl.net >Subject: CCL:A request for help on molecular modeling simulations. > There is an excellent paper by Ajay and Mark Murcko that discusses computational binding energies that may answer some of your general questions. See: J. Med. Chem., 1995, 38, 4953. Jon Erickson DowElanco CAMD From basmith@pollux.chem.umn.edu Thu Jul 17 05:07:41 1997 Received: from pollux.chem.umn.edu for basmith@pollux.chem.umn.edu by www.ccl.net (8.8.3/950822.1) id EAA11449; Thu, 17 Jul 1997 04:15:38 -0400 (EDT) Received: from localhost by pollux.chem.umn.edu via SMTP (950413.SGI.8.6.12/950213.SGI.AUTOCF) for id DAA22716; Thu, 17 Jul 1997 03:15:38 -0500 Date: Thu, 17 Jul 1997 03:15:37 -0500 (CDT) From: "Bradley A. Smith" Reply-To: "Bradley A. Smith" To: chemistry@www.ccl.net Subject: xvibs Version 4 Message-ID: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII xvibs has been rewritten to increase speed and to remove the atom limit. Reductions of the number of passes through the input file and changes in the search algorithm greatly improve speed. The number of atoms which can be handled is now only limited by memory. xvibs has also been extended with an optional third argument which creates palindrome animation files for use with Chime (default settings) rather than the loop animation used in XMol. This new version is available at ftp://ftp.ccl.net/pub/chemistry/software/SOURCES/C/xvibs For more information, read the README or email basmith@pollux.chem.umn.edu. -- Bas ----- Bradley A. Smith basmith@pollux.chem.umn.edu Chemistry Department http://pollux.chem.umn.edu/~basmith/ University of Minnesota (612) 624-1535 From kcross@cas.org Thu Jul 17 11:07:42 1997 Received: from srv01s4.cas.org for kcross@cas.org by www.ccl.net (8.8.3/950822.1) id KAA13703; Thu, 17 Jul 1997 10:54:26 -0400 (EDT) Date: Thu, 17 Jul 1997 10:53:56 -0400 From: kcross@cas.org (Kevin P. Cross Ext. 3192) Message-Id: <9707171053.AA29958@cas.org> Subject: Re: CCL:SUMMARY - Reaction Pathway Programs In-Reply-To: <199707152152.AA20799@interlock.amoco.com> of Tue, 15 Jul 1997 16:51:21 -0500 To: jtgolab@amoco.com Cc: CHEMISTRY@www.ccl.net Folks, Joe has done a nice job gathering and summarizing information about retro-synthesis planning programs. I would like to have this conversion move in a slightly different direction. A lot of these programs have been around for a long time yet it seems that none has really caught on in the market place. What are peoples opinions on why these programs are not routinely used for synthesis planning today? I have a few questions to start out: Do they give too many hypothetical answers but not practical? Do they give too many answers (or repetative answers - same substructure)? Is the software too difficult to use without a lot of training? Does the software fail to reveal anything new to trained synthetic chemists? Is it too expensive or run on the wrong platforms? Does it lack integration with reaction data, availability, etc? Is it too time consuming to run for many users? What can be done to make these programs more useful? Many thanks in advance, Kevin =================================================== Kevin P. Cross, Ph.D. Senior Associate Research Scientist Chemical Abstracts Service (614)-447-3600 Ext. 3192 kcross@cas.org =================================================== From jtgolab@amoco.com Thu Jul 17 10:23:22 1997 Message-Id: <199707152152.AA20799@interlock.amoco.com> From: jtgolab@amoco.com (Joe Golab) Date: Tue, 15 Jul 1997 16:51:21 -0500 To: CHEMISTRY@www.ccl.net Subject: CCL:SUMMARY - Reaction Pathway Programs Cc: jtgolab@amoco.com Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Sender: chemistry-request@www.ccl.net Errors-To: ccl@ccl.net Precedence: bulk Content-Length: 11105 Content-Length: 11106 Hi CCL: Below is the summary of responses to the "retro-synthesis" question I recently asked. Thanks to all who have responded. I have edited some of the answers and so I take full responsibility for any errors. If I get any more answers, I will re-post summary. << Tue Jul 15 16:50:53 CDT 1997 >> Execute Summary of Answers 1) SYNGEN, Jim Hendrickson, Brandeis University 2) CAMEO, Bill Jorgensen, Yale 3) SYNTREE, Commerical Software, Vendor? 4) SYNLIB, Dan Chodosh, may not exist anymore 5) REACCS, MDL 6) CAS's reaction data base 7) Chiron, Steve Hannisan (spl?) of U. of Montreal. 8) LAHSA, E.J. Corey, Harvard U. 9) Unknow, Michael Mavrovouniotis, Northwestern 10) Crossfile, Beilstein :Joe jtgolab@amoco.com (630) 961-7878 -- =================================================== Kevin P. Cross, Ph.D. Senior Associate Research Scientist Chemical Abstracts Service (614)-447-3600 Ext. 3192 kcross@cas.org =================================================== From elrod@chemcomp.com Thu Jul 17 12:07:46 1997 Received: from bobino.sefmedia.com for elrod@chemcomp.com by www.ccl.net (8.8.3/950822.1) id MAA14370; Thu, 17 Jul 1997 12:07:06 -0400 (EDT) Received: from [205.205.162.18] by bobino.sefmedia.com (NTMail 3.02.13) with ESMTP id sa006310 for ; Thu, 17 Jul 1997 12:07:47 -0400 Message-Id: <1.5.4.16.19970717115339.0ea7ccb2@mail.chemcomp.com> X-Sender: elrod@mail.chemcomp.com X-Mailer: Windows Eudora Light Version 1.5.4 (16) Mime-Version: 1.0 Content-Type: text/plain; charset="us-ascii" To: chemistry@www.ccl.net From: "Marc-A. Houle" Subject: Next Edition of the Journal of the Chemical Computing Group Date: Thu, 17 Jul 1997 12:07:47 -0400 The fourth edition of the Journal of the Chemical Computing Group is now available. Feel free to browse through it: http://www.chemcomp.com You'll find new features on MOE Deployment Strategies, Multiple Sequence and Structure Alignment, Object Layout with the SVL Interface Toolkit, and an article by Paul Labute on the A* Search and its Application to Sequence Alignment. As always, you can also find important information on our company and products. Marc Houle Chemical Computing Group elrod@chemcomp.com From dsmith@CTCnet.Net Thu Jul 17 13:07:46 1997 Received: from home.CTCnet.Net for dsmith@CTCnet.Net by www.ccl.net (8.8.3/950822.1) id MAA14631; Thu, 17 Jul 1997 12:33:24 -0400 (EDT) Received: from fock by home.CTCnet.Net (SMI-8.6/SMI-SVR4) id MAA03384; Thu, 17 Jul 1997 12:26:29 -0400 Message-Id: <3.0.1.32.19970717123431.009c5520@pop.dasgroup.com> X-Sender: dsmith@pop.dasgroup.com X-Mailer: Windows Eudora Light Version 3.0.1 (32) Date: Thu, 17 Jul 1997 12:34:31 -0400 To: CHEMISTRY@www.ccl.net, kcross@cas.org (Kevin P. Cross Ext. 3192) From: "Douglas A. Smith Ph.D." Subject: Re: CCL:SUMMARY - Reaction Pathway Programs In-Reply-To: <9707171053.AA29958@cas.org> References: <199707152152.AA20799@interlock.amoco.com> Mime-Version: 1.0 Content-Type: text/plain; charset="us-ascii" To give my personal response to Kevin's questions: At 10:53 AM 7/17/97 -0400, you wrote: > >What are peoples opinions on why these programs are not >routinely used for synthesis planning today? Basic answer is that synthetic organic chemists tend to know the literature pretty well for the types of reactions and transformations they routinely need. So, unless you run into trouble and can't do what you want/need, there is little incentive to going to a computer, running a program you may not be too familiar with or that may be difficult to use, and getting alternatives. Furthermore, the typical attitude (again, speaking as one who did synthesis and ran a synthesis group for many years) is "Try it. Just because it worked/didn't work in the literature doesn't mean it will/won't work on your compound!" Furthermore, a typical approach is to try two or three reactions/reagents at a time, then compare the results for ease and yield. > >I have a few questions to start out: > >Do they give too many hypothetical answers but not practical? Probably the opposite it true. Then the bench chemist must read all 100+ answers, down select him/herself, and try a few anyway. >Do they give too many answers (or repetative answers - same substructure)? Same answer as above. >Is the software too difficult to use without a lot of training? It sure used to be. SYNTREE, from what I remember, had a reasonable GUI under Windows. I don't know about MDL's software. Also, many of these programs came out of the old VAX era, which is a horror for bench chemists used to MacIntosh or now days Windows GUIs. >Does the software fail to reveal anything new to trained synthetic chemists? Isn't this always the case in any expert system? And these programs are truly expert systems, typically rule based (e.g. CAMEO, LAHSA). It is not trivial to develop a non-rule-based system. >Is it too expensive or run on the wrong platforms? See above for my limited knowledge answer. >Does it lack integration with reaction data, availability, etc? In my experience, all this is available. >Is it too time consuming to run for many users? Yes. > >What can be done to make these programs more useful? Ah, the good and important question. I wish I had the answer, I could make a few bucks! > >Kevin P. Cross, Ph.D. >Senior Associate Research Scientist >Chemical Abstracts Service Doug Smith -- Dr. Douglas A. Smith, President and CEO | voice: (814) 255-7859 The DASGroup, Inc. | fax: (814) 255-3517 1732 Lyter Drive, 2nd Floor | email: dsmith@dasgroup.com Johnstown, PA 15905 | WWW: http://www.dasgroup.com Contract R&D specialists in modeling, simulation, synthesis and risk assessment for chemistry, materials science, and biotechnology. From Marc-Andre.Delsuc@cbs.univ-montp1.fr Thu Jul 17 13:14:23 1997 Received: from tome.cbs.univ-montp1.fr for Marc-Andre.Delsuc@cbs.univ-montp1.fr by www.ccl.net (8.8.3/950822.1) id MAA14473; Thu, 17 Jul 1997 12:17:44 -0400 (EDT) Received: from supreme.cbs.univ-montp1.fr by tome.cbs.univ-montp1.fr with SMTP (1.37.109.4/16.2) id AA24048; Thu, 17 Jul 97 18:41:26 +0200 X-Sender: mad@tome.cbs.univ-montp1.fr Message-Id: Mime-Version: 1.0 Content-Type: text/plain; charset="us-ascii" X-Mailer: Eudora F1.5.4b5 Date: Thu, 17 Jul 1997 18:13:04 -0800 To: chemistry@www.ccl.net From: Marc-Andre.Delsuc@cbs.univ-montp1.fr (M.A. Delsuc) Subject: New version of the NMR software Gifa Hi all Netters, GIFA is an NMR processing program developped in my laboratory. It runs on most UNIX machine (including Linux), and permit to process display and analyse multidimensional NMR data (up to 3D). There is today more than 100 registered users. A new version of the Gifa has just been made available : Version 4.20 - dated 15 July 1997 Check the WEB home-page : http://www.cbs.univ-montp1.fr/GIFA/ from which you can acces to several information, screen-shots, as well as the complete on-line manual. ============================================================================== NEW with this version --------------------- The most prominent new features of this version are : - A Complete DOSY processing module. The processing is based on the Maximum Entropy inversion of the Laplace transform. This permits to process polydisperse species as well as monodisperse ones. The module can also be used to process multiexponential relaxation data. It is distributed with a complete manual, and a mathematical introduction. - a general Fitter which can fit your data to any provided function. (T1, T2, DOSY, etc...) - the assignment module has been extensively debugged and enhanced. - access to Varian files has been extended works now for Linux, access to files in float, reads parameters, etc... ============================================================================== DISTRIBUTION ------------ This version is distributed under a licence. There is no fee for academic laboratories, however the licence requires that you refer to Gifa in any published work which depend in some manner on the Gifa program. The program, as distributed is fully workable, a small annoying message just recall you to ask for a licence. This program can be downloaded by anonymous FTP on Internet, the home site is the following address : ftp://www.cbs.univ-montp1.fr/pub/gifa_v4 There is also mirror sites : In Japan : at Institute for Molecular Science, Okazaki, ftp://ftp.ims.ac.jp/pub/unix/chem/gifa gopher://gopher.ims.ac.jp:70/11/tmp/pub-link/unix/chem/gifa In US. : Ohio Supercomputer Center, Colombus ftp://www.ccl.net/pub/chemistry/software/UNIX/gifa/ As distributed, the program works on HP/HP-UX, SGI/IRIX, PC/Linux SUN/Solaris RS6000/AIX. Best Regards M.A.Delsuc _________________________________________________________________________ Marc-Andre' Delsuc Centre de Biochimie Structurale Marc-Andre.Delsuc@cbs.univ-montp1.fr Faculte de Pharmacie tel : (33) (0) 467 04 34 36 15 av, Charles Flahault fax : (33) (0) 467 52 96 23 34060 Montpellier cedex www : http://www.cbs.univ-montp1.fr FRANCE From Lchen@mdli.com Thu Jul 17 16:07:46 1997 Received: from mdli.com for Lchen@mdli.com by www.ccl.net (8.8.3/950822.1) id PAA15976; Thu, 17 Jul 1997 15:15:39 -0400 (EDT) Received: from puffin.mdli.com ([191.254.19.10]) by mdlgate.mdli.com with ESMTP id <17466>; Thu, 17 Jul 1997 12:14:26 -0700 Received: from gimli.mdli.com by puffin.mdli.com (8.8.5/BCH1.0) id LAA06260; Thu, 17 Jul 1997 11:54:41 -0700 (PDT) Received: from ostrich (ostrich.mdli.com) by mdli.com (PMDF V5.1-5 #15780) with SMTP id <01ILCCVMYC5GHSL5FO@mdli.com> for CHEMISTRY@www.ccl.net; Thu, 17 Jul 1997 12:15:23 PDT Date: Thu, 17 Jul 1997 11:07:39 -0700 From: "Lingran Chen, x1305" Subject: Re: CCL:SUMMARY - Reaction Pathway Programs Sender: lchen@mdli.com To: CHEMISTRY@www.ccl.net Cc: lchen@mdli.com Message-id: <33CE5F6B.446B@mdli.com> Organization: MDL Information Systems, Inc. MIME-version: 1.0 X-Mailer: Mozilla 3.01Gold (X11; I; IRIX 6.2 IP22) Content-type: text/plain; charset=us-ascii Content-transfer-encoding: 7bit Douglas A. Smith Ph.D. wrote: > > To give my personal response to Kevin's questions: > > At 10:53 AM 7/17/97 -0400, you wrote: > > > >What are peoples opinions on why these programs are not > >routinely used for synthesis planning today? > > Basic answer is that synthetic organic chemists tend to know the literature > pretty well for the types of reactions and transformations they routinely > need. So, unless you run into trouble and can't do what you want/need, > there is little incentive to going to a computer, running a program you may > not be too familiar with or that may be difficult to use, and getting > alternatives. Furthermore, the typical attitude (again, speaking as one > who did synthesis and ran a synthesis group for many years) is "Try it. > Just because it worked/didn't work in the literature doesn't mean it > will/won't work on your compound!" Furthermore, a typical approach is to > try two or three reactions/reagents at a time, then compare the results for > ease and yield. In May 1995 there was a Workshop on Computer Aided Synthesis held at Goslar, Germany, organized by the bench organic chemists. Both bench organic chemists and computer chemists attent the meeting, including many of the leaders in the area of Computer Aided Synthesis Design (CASD) in the world. The main focus of the workshop was to review the status of CASD systems and to find the cause of the unpopularity of those systems in the chemistry community and to look for the good ways to promote the wider acceptance of this kind of software. Some experts in the field suggested that introducing the seminar on CASD in the universities could enable the new generation of the chemists to become familiar with this kind of "new" tools. On that meeting I made a simply comparison of CASD systems with other "chemical" software to reveal one of the main reasons why most of the bench chemists are not willing to accept CASD programs: 1. Why are chemists want to use computer to search literature? Because chemists are unable to get *manually* the newest, most comprehensive literature on a specific topic they are interested in in, but computer can help them to do so. 2. Why are chemists willing to use "quantum chemistry" programs? Are they good enough? The answer to the second question is No. There are many "theoretical calculation" programs/methods, but none of them are really "theoretically" correct! It is not unusual in this area that different approaches produce different answers to the same problems. Chemists still have to reply heavily on the experimental results to confirm the results generated by the computer programs. The answer to the first quetion is quite simply: No one, even the brightest chemist in the world, is willing, able, to do a *manual* "ab initio calculation" for even a small molecule consisting of a few atoms on the paper! But, computer can do that for you, though the results may be unreliable. 3. Now, how about CASD programs? In my opinion, a few CASD systems are at least as mature as those of "quantum chemistry" programs. Unfortunately, chemists are able to *manually* design the syntheis routes on the paper! It is their traditional, main, job! > >I have a few questions to start out: > > > >Do they give too many hypothetical answers but not practical? > > Probably the opposite it true. Then the bench chemist must read all 100+ > answers, down select him/herself, and try a few anyway. SYNGEN (http://syngen2.chem.brandeis.edu/syngen.html), for example, is able to sort the generated routines according to different criteria, enabling chemists to check the first a few route candidates in the sorted lists. > >Do they give too many answers (or repetative answers - same substructure)? > > Same answer as above. > > >Is the software too difficult to use without a lot of training? > > It sure used to be. SYNTREE, from what I remember, had a reasonable GUI > under Windows. I don't know about MDL's software. MDL's (http://www.mdli.com/) desktop programs have nice GUI. > Also, many of these > programs came out of the old VAX era, which is a horror for bench chemists > used to MacIntosh or now days Windows GUIs. I ported SYNGEN (http://syngen2.chem.brandeis.edu/syngen.html) from VAX to PC/Linux, its GUI was written in Tcl/Tk. The program is very easy to use indead and the GUI are also nice. > >Does the software fail to reveal anything new to trained synthetic chemists? > > Isn't this always the case in any expert system? And these programs are > truly expert systems, typically rule based (e.g. CAMEO, LAHSA). It is not > trivial to develop a non-rule-based system. But, SYNGEN and also some other systems are able to generate *automatically* some *new* chemistry! > >Is it too expensive or run on the wrong platforms? > > See above for my limited knowledge answer. > > >Does it lack integration with reaction data, availability, etc? > > In my experience, all this is available. > > >Is it too time consuming to run for many users? > > Yes. Not completely correct. SYNGEN is quite fast. > > > >What can be done to make these programs more useful? > > Ah, the good and important question. I wish I had the answer, I could make > a few bucks! There are still many things one can do. Of cause, different CADSD systems have different problems. For example, the integration of the SYNGEN system with Prof. Hendrickson's reaction retrieval program COGNOS is under way. Dealing with stereochemistry is also need to be done. By the way, the CASD systems like SYNGEN may find their applications in preparation of Combinatorial chemistry libraries. > > > >Kevin P. Cross, Ph.D. > >Senior Associate Research Scientist > >Chemical Abstracts Service > > Doug Smith > -- > Dr. Douglas A. Smith, President and CEO | voice: (814) 255-7859 > The DASGroup, Inc. | fax: (814) 255-3517 > 1732 Lyter Drive, 2nd Floor | email: dsmith@dasgroup.com > Johnstown, PA 15905 | WWW: http://www.dasgroup.com ********************************************************** Lingran Chen, Ph.D. Senior Scientific Programmer MDL Information Systems, Inc. 14600 Catalina Street San Leandro CA 94577 Phone: (510) 895-1313, Ext. 1305 FAX: (510) 614-3616 Email: LCHEN@MDLI.COM URL: http://www.mdli.com http://syngen2.chem.brandeis.edu/~chen/lingran.html ********************************************************** From brunob@helix.nih.gov Thu Jul 17 17:07:45 1997 Received: from mgcct6.nci.nih.gov for brunob@helix.nih.gov by www.ccl.net (8.8.3/950822.1) id QAA16584; Thu, 17 Jul 1997 16:56:04 -0400 (EDT) Received: from mgcct6 (localhost [127.0.0.1]) by mgcct6.nci.nih.gov (950413.SGI.8.6.12/950213.SGI.AUTOCF) via SMTP id RAA12336 for ; Thu, 17 Jul 1997 17:17:51 -0400 Sender: brunob@helix.nih.gov Message-ID: <33CE8BFF.ABD@helix.nih.gov> Date: Thu, 17 Jul 1997 17:17:51 -0400 From: Bruno Bienfait Organization: National Cancer Institute X-Mailer: Mozilla 3.01SGoldC-SGI (X11; I; IRIX 6.3 IP32) MIME-Version: 1.0 To: Computer Chemistry List Subject: Object-oriented means for computational chemistry programming Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit Using an OO language does not necessarily imply OO programming. For example, I have found a molecular editor written in Java (MoleculeEditor_1_0.java from the ftp archive at www.ccl.net). Here follows a comment from the program : /* * This is the Molecule_1_0 class. It is used to store and handle all the aspects * of a molecule creation, modifications, drawing, etc... * Everything is stored in arrays. The maximum size is 100 atoms and * 250 bonds. It is never checked if these limits are passed! */ The MoleculeEditor_1_0.java is a 2000 lines file with 93 case statements and three classes. My point is that this program is written in Java but in a Fortran style. Those who are interested in learning to "think in OO" might have a look at Smalltalk express (http://www.objectshare.com/seinfo.htm), which is a free implementation of the Smalltalk programming language. regards, Bruno -- [ Bruno Bienfait, Ph. D. Laboratory of Medicinal Chemistry ] [ National Cancer Institute ] [ Email : brunob@helix.nih.gov National Institutes of Health ] [ Phone : (301) 402-3111 Building 37, Room 5B20 ] [ Fax : (301) 496-5839 Bethesda Maryland 20892 , USA ] [ WWW : http://schiele.organik.uni-erlangen.de/Bruno_Bienfait ]