From AZHARI%EGFRCUVX.BITNET@phem3.acs.ohio-state.edu Tue Sep 7 13:29:40 1993 Date: Tue, 07 Sep 1993 13:29:40 +0000 (O) From: AZHARI%EGFRCUVX.BITNET@phem3.acs.ohio-state.edu Subject: address of J. Mol. Strcut. (THEOCHEM) To: chemistry@ccl.net Message-Id: <01H2O2UHNHWM00017W@EGFRCUVX.BITNET> Dear Netters: I want to publish a paper in the J. Mol. Struct. (THEOCHEM). The latest issue we have in Egypt is for 1985 and I want only to make sure that the address I should send the paper to is still valid. The address is: Prof. W. J. Orville-Thomas, Department of chemistry and applied Chemistry, The University, Salford M5 4WT, Lancs., Great Britain. Can anyone tell me if this address is still valid and if not what is the correct address I should send the paper to. Thank you a lot for you help. Adel El-Azhary Chemistry Department Cairo University Bitnet: Azhari@EGFRCUVM From ravishan@tulip.wcc.wesleyan.edu Tue Sep 7 04:54:43 1993 Date: Tue, 7 Sep 1993 08:54:43 -0400 Message-Id: <9309071254.AA14155@tulip.wcc.wesleyan.edu> From: G. Ravishanker To: wsonnen@alnitak.usc.edu Subject: Re: presentation of data Wayne There are a couple of excellent books on this subject by Ed Tufte. The Visual Display of Quantitative Information Published by Graphic Press. is one of them. I do not have the title for the other one. Ravi From rickr@scripps.edu Mon Sep 6 23:00:08 1993 Date: Tue, 7 Sep 93 06:00:08 PDT From: rickr@scripps.edu (Rick Ross) Message-Id: <9309071300.AA06737@ppg.Scripps.EDU> To: chemistry@ccl.net Subject: molecular_struct_database Folks, Greetings. I was wondering if anyone might know of databases containing prebuilt molecular structures for organic molecules that are in a form readable to Microsoft Word. I know that one can build a chemical structure using one of the commercial packages and then use things like "clipboard" to move it from the structure building package to Microsoft Word but we were wondering if anyone had compiled databases of structures so time could be saved by not having to go through the building step. I would be glad to summarize any responses for the net. Thanks in advance for any help. Regards, Rick Ross PPG Industries P.O. Box 9 Allison Park, PA 15101 (412) 492-5359 rickr@ppg.scripps.edu From rs0thp@RohmHaas.Com Wed Sep 8 43:30:04 1993 From: rs0thp@RohmHaas.Com (Dr. Tom Pierce) Message-Id: <9309071307.AA19637@monte.br.RohmHaas.Com> Subject: Re: Elementary Text on Molecular Mechanics To: chemistry@ccl.net Date: Tue, 7 Sep 1993 09:07:04 +22305823 (EDT) Previously, M. Nicklaus wrote: > > Hence my question: Does anyone know of a VERY ELEMENTARY introductory text > on molecular mechanics, preferrably in the context of drug development? > I suggest that you review articles from J. Chem. Education. In specific I refer to 'Molecular Mechanics The method and its underlying philosophy', vol 59, #4 1982 pp 269-274. and the following article (more complex) 'Molecular Mechanics Illustrations of it application', 59,4, 1982, pp 275-276. I suspect there may be more recent J. Chem. Ed. articles as well. -- Sincerely, Thomas Pierce, Internet Address: THPierce@RohmHaas.Com Official Disclaimer:"The opinions expressed are those of the writer and not the Rohm and Haas Company." From mmconn@esau.mit.edu Tue Sep 7 05:45:16 1993 Date: Tue, 7 Sep 93 09:45:16 -0400 From: mmconn@esau.mit.edu (morgan conn) Message-Id: <9309071345.AA16983@esau.mit.edu> To: chemistry@ccl.net Subject: drug modeling A couple of weeks ago I posted a request for information on the modeling/ handling/design of drugs. Here are the results: THE INQUIRY: I am interested in computational packages for drug design (ones that include minimization, database management, and pharmacophore prediction). I've seen vague mentions of a number of these at ACS meetings and such (too bad I've missed the latest), but want to find out from 'those in the know' what is good/ bad/ugly. Can anyone tell me something about programs of this nature? I would especially be interested in hearing from those on the list in the pharmaceutical industry. THE RESPONSES: __________________________________________________________________________________ >From terry@wag.caltech.edu Thu Aug 26 21:30:52 1993 __________________________________________________________________________________ >From berkley@wubs.wustl.edu Fri Aug 27 09:08:27 1993 DISCO can give suggestions as to the pharmacophore, but it depends on your faith in minimized structures being the conformation that actually bind at the receptor. RECEPTOR (I or II) will verify pharmacophore models faster than you can imagine. It will also produce very low energy conformers for downstream study. Both are sold by TRIPOS, and are close to free to educational sites. Berkley Shands ____________________________________________________________________________________ >From balbes@osiris.rti.org Fri Aug 27 09:21:18 1993 I have recently finished writing a chapter for "Reveiws in computational Chemisty" on modern methods of computer aided drug design, complete with names and contact addresses for software companies. It will be coming out later this fall. You might also try the computational chemistry yellow pages,' which lists about all the software currently available. Let me know if you would like more information on either of these sources. Lisa Lisa Balbes Osiris Consultants balbes@osiris.rti.org 2229B Hedgerow Rd, Columbus, OH 43220 614-442-9850 FAX: 614-451-5860 ____________________________________________________________________________________ >From JOHNSON_DOUGLAS_W@Lilly.com Fri Aug 27 15:37:28 1993 In response to your query on the OSC bbs, I'd recommend you take a look at Catalyst, distributed by BIOCAD corp. I've recently started using it and it seems to be able to do everything you want. Specifically what you do is input a series of compounds, the more structural variation the better, that have pharmacological testing results. The predictor needs to have at least 20 compounds with activity over 3 orders of magnitude. The program will generate conformational possibilites for each molecule and store them. You fill out a spreadsheet with the activity data and the program will then generate a "hypothesis" of the pharmacophore based upon structure and activity data. The more active compounds are weighted heavier in the process. You ask the program to look for "features" where there is overlap in the 3D structural data. The features include hydrophobic regions, H-bond acceptor/ donor regions, ionizable regions. The output comes up as a 3D arrangement of the best fits of these regions. You can see how each compound in this training set fits to the hypothesis. The minimization aspect is crude MM2 type but seems to be sufficient. It is a memory hog; it takes 40MB of memory on an Indigo to bring it up. Supposedly the next version has been cleaned up a lot. Contact: BioCAD Corporation 1390 Shorbird Way Mountain View, CA (415) 903-3900 Hope this helps you. Sincerely, Doug Johnson Lilly Research Labs Indianapolis, IN 46285-1513 dwj@lilly.com _______________________________________________________________________________ >From tudor@wucmd.wustl.edu Sat Aug 28 14:39:56 1993 I guess it depends on the available data that you wish to tackle with. 1. If you have a series of cpds that have reliable functional and binding data, you may wish to use QSAR methodology (that is, Quant. Struct-Act. Relat), and i suggest CoMFA (Comparative Molecular Field Analysis) by Cramer et al, available from Tripos Associates. Their package is called Sybyl, and in the 3D-QSAR field is one of the best available, as it comes with a good chemometric package (CoMFA uses Partial Least Squares method developed by Wold et al; enhancements are probably available soon - PLS optimization methods from Clementi et al). When you use CoMFA you need an alignment (that is, conformational analysis and superposition rules). You can use the Tripos force-field, but also MM2 (if you buy it), and several minimizers are available (including Simplex, BFGS, conjugate gradient). If you have peptides, you could use Amber. 2. If you have just a lead compound and a rather scarce set of data, you can either a. scan the literature and gather some more or b. ask your colleagues if previous attempts were made in the same directin or c. get Biosym & Apex 3D (from Golender et al), that would help you with pharmacophore ID and assist you in your (Q)SAR efforts. Biosym has also a very good package for ligand design - Ludi (from Hans Boehm), which may assist you if you have a known binding site. Force fields: CVFF, Amber plus some other options. 3. For database management, you may wish to use software available >from Daylight, which is specifically designed for this (& other) purpose(s). PS: I did not include phone numbers or email, since i do not wish this to sound like an advertisement. There's other software out there that does similar things, but i tried to get you first (hands on) experience - so the rest is not ignored, it simply means i did not use it. Tudor Oprea (tudor@wucmd.wustl.edu) Research Associate Center for Molecular Design, Washington University, St. Louis PPS: you could have seen Tripos, Bisoym and Daylight expose their software at the ACS meeting exposition, in Chicago, this week! For those who are looking for decisions, i suggest you take your time and see the next expo, at the next ACS meeting, spring 94. ___________________________________________________________________________ >From MARTIN@cmda.abbott.com Mon Aug 30 15:45:31 1993 To my mind, Sybyl is the only game in town. We switched from 10 years of in-house software to Sybyl this year. The switch I thought would take 18 months--instead it took 3. Sybyl was designed for the small-molecule modeler, most specifically the person interested in drug design. It has nice facilities for looking at crystal packing, a good thing to help one think about intermolecular interactions. Additionally, it has 3D searching and the newest is the molecular spreadsheet. From the spreadsheet one can integrate biological and modeling information. Commands can be applied to every molecule in a spreadsheet with the results appearing in a column. @@@@@@@@@@@ Yvonne Martin, Senior Project Leader @ Computer Assisted Molecular Design Project @@@@@@@@ @ D-47E, AP9A-LL @ @ Abbott Laboratories @ @ One Abbott Park Road @@@@@@@@@@ Abbott Park, IL 60064 Phone: 708 937-5362 FAX: 708 937-2625 ________________________________________________________________________________ >From moret@far.ruu.nl Sun Aug 29 06:15:47 1993 Here are some refs. to programs for computer-aided molecular design. Most of the programs are commercially available. Some have been developed in the industry and might not be distributed. Check out J.CAMD and the Reviews in Computational Chemistry Series. COSMIC Nottingham, Cambridge, London dr. J.G. Vinter, Cambridge Morley et al. J.CAMD 5 1991 475 GRID Molecular Discovery Ltd., West Way House, Elms Parade, Oxford OX2 9LL UK dr. P. Goodford, Oxford J.Med.Chem. 23 1985 849 LUDI, Biosym Technologies Inc., 10065 Barnes Canyon Road, Suite A, San Diego CA 92121 dr. H.J. Boehm, BASF J.CAMD 6 1992 61 and 593 DOCK UCSF dr. I. Kuntz, UCSF des Jarlais et al. J.Med.Chem. 29 1986 2149 GROW Upjohn Company dr. W.J. Howe, Upjohn Moon et al. Proteins: Struct. Funct. Genet. 11 1991 314 HOOK York, Harvard, possibly Molecular Simulations Inc.? dr. R. Hubbard, York MCSS Harvard, possibly Molecular Simulations Inc.? dr. M. Karplus, Harvard Miranker et al. ? CoMFA Tripos Associates, 1699 Hanley Road, St. Louis, Missouri 63144 Also Receptor and Leapfrog coming up? dr. R. Cramer III, Tripos JACS 110 1985 5959 APEX Biosym dr. V. Golender Golender and Rosenblit Logical and Combinatorial Algorithms for Drug Design Research Studies Press, Letchworth 1983 ALADDIN Daylight Chemical Information Systems, 3951 Claremont St., Irvine, CA 92714 dr. Y. Martin, Abbott van Drie et al. J.CAMD 3 1989 225 CAVEAT, ILIAD, TRIAD UCB dr. P. Bartlett, UCB Bartlett et al. in Chemical and Biological Problems in Molecular Recognition ? SPERM Organon International dr. V. van Geeresteijn, Organon JCAMD 1991? AAA Washington University, St. Louis dr. G. Marshall, WU CMD Marshall et al. Comp.Ass.Drug Design.Symp. 112 1979 Ch.9 205 MTD Faculty of Pharmacy, Timisoara, Rumania dr. Z.Simon Simon et al. J.Theor.Biol. 66 1977 485 ?? Cambridge dr. P. Dean, Cambridge Chau and Dean J.CAMD 1992 several articles ?? Nishibata and Itai Tetrahedron 47 1991 8985 I haven't got all papers at hand at the moment. Professor R. Hubbard organised a meeting on this topic last march for the Molecular Graphics Society. I am afraid I had to miss it. He may be the person who could give authoritative pointers, though. Regards, Ed Moret ------------------------------------------------------------------------- E.E. Moret (@more@) moret@far.ruu.nl Computational Medicinal Chemistry/Department of Pharmaceutical Chemistry Faculty of Pharmacy/Utrecht University/the Netherlands Telephone (31-30)536979/536958 Facsimile (31-30)516674 ------------------------------------------------------------------------- Thanks to all who responded. -mmc ********************************************************* Morgan Conn MIT Chemistry, 18-148, Cambridge, MA 02139; mmconn@esau.mit.edu, 617.253.6438, 617.253.7929 (fax) ********************************************************* From system@alchemy.chem.utoronto.ca Tue Sep 7 08:05:18 1993 Date: Tue, 7 Sep 93 12:05:18 -0400 From: system@alchemy.chem.utoronto.ca (System Admin (Mike Peterson)) Message-Id: <9309071605.AA15519@alchemy.chem.utoronto.ca> To: chemistry@ccl.net Subject: Re: address of J. Mol. Strcut. (THEOCHEM) J. Mol. Struct. (THEOCHEM) articles should be sent to: Prof. I.G. Csizmadia, Department of Chemistry, University of Toronto, 80 St. George St., Toronto, Ontario, Canada M5S 1A1 From richard@iris26.biosym.com Tue Sep 7 03:47:33 1993 Message-Id: <9309071747.AA07113@iris26.biosym.com> To: CHEMISTRY@ccl.net Subject: Re: Natural conformation of protein=global minimum? Date: Tue, 07 Sep 93 10:47:33 -0700 From: Richard Macdonald > From: maloneyhuske%phvax.dnet@smithkline.com (Keith MaloneyHuss x6083) > To: "chemistry@ccl.net"%INET.dnet@smithkline.com > Subject: Natural conformation of protein=global minimum? > Sender: chemistry-request@ccl.net > Errors-To: owner-chemistry@ccl.net > Precedence: bulk > > Is it assumed that the natural conformation of all proteins is > the free energy global minimum? If so, why? > It must be at least a local minimum, but why assume there is no > possible lower energy state? It is obviously not easily > accessable or it would be the natural configuration. Aren't > there chaperones to assist folding that determine the final conformation, > and thus select conformation based not upon absolute energy minimum criteria > but rather find a good (read very stable) local minimum which is in the > required shape for the protein's function? > > --keith > This is a very good and topical question. It was proposed by several speakers at a recent conference (MacroMolecules, Genes, and Computers, Waterville Valley, N.H., Aug 1993) that proteins are in a global minimum (at least small, compact, re-foldable proteins). A good discussion is the paper by Ruben A. Abagyan, "Towards protein folding by global energy optimization", FEBS 325, 17-22 (1993). The idea at the meeting seemed to be that the force fields were incomplete for proteins, and if the proper functions were used (electrostatics, hydrophobicity, contact surface, entropy, etc) the true free energy of the protein structure would be the global minimum. I must admit I was surprised by these ideas, and had assumed (like most other people I know) that proteins were in a local (but not necessarily global) minimum. -----> richard *********************************************************** Richard D. Macdonald, Ph.D. voice: (619) 546-5527 Biosym Technologies internet: richard@biosym.com 9685 Scranton Road San Diego, CA 92121-2777 *********************************************************** From tracy@tango.austin.unimelb.edu.au Wed Sep 8 20:38:39 1993 Date: Wed, 8 Sep 93 10:38:39 +1000 From: tracy@tango.austin.unimelb.edu.au (Tracy Nero) Message-Id: <9309080038.AA09023@tango.austin.unimelb.edu.au> To: chemistry@ccl.net Subject: Address of J. Mol. Struct. (THEOCHEM.) According to the fliers sent out by Elsevier Science Publishers you can send manuscripts to any one of their receiving centres, these are listed: Prof I. G. Csizmadia Lash Miller Chemical Laboratories 80 St. George Street, University of Toronto, Toronto M5S 1A1 Canada ********************* Prof. C. E. Dykstra Dept of Chemistry, (IUPUI) Indiana University - Purdue University at Indianapolis, 402 N Blackford Street, Indianapolis, IN 46202-3274 USA ******************* Prof. W. J. Orville-Thomas Dept. of Chemistry, University of Salford Salford, M5 4WT UK ******************* Prof. J. L. Rivail Laboratorie de Chimie Theorique, Universite Nancy I, BP 239, 54506 Vandoeuvre-les-Nancy France ****************** (for Eastern European authors only) Prof. H. Ratajczak Institute of Chemistry, University of Wroclaw, ul Joliot Curie 14, 50-383 Wroclaw Poland ******************** Further information can be obtained from Elsevier Editorial Services, Mayfield House, 256 Banbury Road, Oxford, OX2 7DH, England. telephone 0865 54252 fax 0865 516120 or 56472 Also, papers can be submitted to THEOCHEM on floppy disks, for a guide on how to do this contact the editorial services at the above address. -T. Nero Dept of Medicine University of Melbourne Austin Hospital Heidelberg 3084 Victoria Australia From P84031@VM.BIU.AC.IL Tue Sep 7 22:01:16 1993 Date: Tue, 07 Sep 1993 16:31:16 +0530 (IST) From: "Dr. Pinchas Aped" Subject: Alpha-DEC Gaussian-92 Version To: CHEMISTRY@ccl.net Message-Id: <01H2ONXF675I8WXDTU@phem3.acs.ohio-state.edu> Dear Netters: As I understand, an ALPHA-DEC version of Gaussian-92 has been announced a few months ago. Has anybody gained any experience with this version, especially with regards to CPU yields for heavy IO jobs, in comparison with other platforms (such as RS6000)? Any other information regarding the ALPHA G92 version will be greatly appreciated. I will post a summary of the responses. Thanks, Pinchas Aped ------------------------------------------------------------------------ Dr. Pinchas Aped Tel.: (+972-3) 531-8634 Department of Chemistry FAX : (+972-3) 535-1250 Bar-Ilan University E-Mail: P84031@BARILVM (bitnet) 52900 Ramat-Gan, ISRAEL aped@gefen.cc.biu.ac.il ------------------------------------------------------------------------