From marty@ionchannel.med.harvard.edu Tue Sep 28 18:42:16 1993 Date: Wed, 29 Sep 93 01:42:16 -0700 From: marty@ionchannel.med.harvard.edu (Marty Gallagher) Message-Id: <9309290842.AA01075@ionchannel.med.harvard.edu> To: CHEMISTRY@ccl.net Subject: torsion energies in conjugated systems Hello, SInce I am new to this group, I thought I would preface my question with an introduction. I am an MD/PhD student who is interested in the mechanism by which small organic molecules recognize the nicotinic acetylcholine receptor. The methods we use include protein chemistry, organic synthesis, molecular biology, electrophysiology and (just starting) molecular modeling. SInce the structure of the receptor has not been solved below 9 A, I am using the modeling for a thinking tool rather than for hard analysis. Now for the question... Does anyone know a forcefield which includes a term for torsional energy in a conjugated system? Specifically, I am interested in rotating the carbonyl in acetophenone out of plane with the phenyl ring. MOPAC geometry optimization places the carbonyl in the plane of the ring. Without running a dozen MOPAC runs, can I get an estimate of what the energy would be out of the plane? Thanks in advance, =================================================================== | | | Martin J. Gallagher | | Dept of Neurobiology | | Harvard Medical School | | 220 Longwood Ave | | Boston, MA 02115 | | (617) 432-1729 | | | | marty@ionchannel.med.harvard.edu | | | =================================================================== From martin@biochem.kth.se Wed Sep 29 12:04:01 1993 Message-Id: <9309290901.AA01173@kiev.physchem.kth.se> Date: Wed, 29 Sep 1993 11:04:01 +0100 To: chemistry@ccl.net From: martin@biochem.kth.se (Martin Norin) Subject: Re: reviewers and computational resources >In recent weeks I have received, either in my capacity as an author or as >an editor, comments on manuscripts and proposals which bother me somewhat. >In particular, referees have made statements suggesting that current hardware >and software are such that the level of theory in a particular study needs >to be increased, i.e. the reviewer believes that the problem was/will be >attacked at too low a level of theory. Dear Computational chemists, I do agree with Dr. Smith and I have experienced similar trends. In my opinion theoretical work as well as experimental should be judged by some kind of value of explicability. The value of a work which explains some interresting feature of the nature is independent of the complexity of the method used. I do not care so much whether a high level of ab initio in connection with 750 Mhz 3-d NMR data or a simple hand made ball and stick model in connection with TLC data have been used if they explain the same thing. Rather a very simple model might be prefered over a very complex if the explicability level is the same. A very complex model might be hard to rationalise and make understandable to people outside your own field. Yours, Martin Norin e-mail:martin@biochem.kth.se Dept. Biochem. KTH 100 44 Stockholm From chp1aa@surrey.ac.uk Wed Sep 29 11:08:21 1993 From: Mr Andrew D Allen Message-Id: <9309291040.AA13010@central.surrey.ac.uk> Subject: RE: reveiews / resources To: chemistry@ccl.net Date: Wed, 29 Sep 93 11:40:09 BST My two penneth worth, Here at Surrey we have very limited resources, we have to do time vs quality of output studies, to justify whether going to another level of accuracy is worth the computer time. If we can get some idea of the trends in our work at a low level of accuracy, then are we justified to go to greater accuracy to still show these trends. Admittedly for those developing new theory, going to high levels of accuracy is perhaps justified. The whole issue is resource dependant, if you have access to loads of money and have the computing resources available then by all means go to the higher level of accuracy. If you only have a SG indigo which is shared between 5 other researchers then you have to settle for the lower level of accuracy. PS. The summary for the DFT request will be going onto out ftp server, when the ftp server is back up and running. From CHEMNET%SUYARS.BITNET@phem3.acs.ohio-state.edu Wed Sep 29 13:08:45 1993 Date: 27 Sep 1993 11:54:09 MSK From: CHEMNET%SUYARS.BITNET@phem3.acs.ohio-state.edu Subject: ANOTHER PLEAD FOR HELP To: CHEMISTRY@ccl.net Message-Id: <01H3IIP8SZZM8X1R5A@phem3.acs.ohio-state.edu> DEAR COMP. CHEMISTS ||| PLEASE: THOSE WHO 1. INTENDED TO PARTICIPATE IN SOWTH-WEST THEORETICAL CHEMISTRY CONFERENCE (12 NOV., TEXAS) AND 2. CAN RECEIVE A FILE OF "WORD FOR WINDOWS, V 2.0" OR "FOR DOS V 5.5" AND THEN MANIPULATE WITH IT, CONTACT WITH ME, ALEXEY SOKOLOV (YAROSLAVL UNIV., RUSSIA). MY E-MAIL: CHEMNET@SUYARS.BITNET (THE REASON: WE HAVE NO MAC'S (ALL ARE IBM BIGOTS IN RUSSIA) I CAN'T ATTENT THE PARTY AND WANT SOMEONE TO TAKE MY POSTER AND STICK IT SOMEPLACE THERE. ORGANIZERS HAVE NO OBJECTIONS. THANX & BEG MY PARDON. ALEXEY From J_BROWN@uvmvax.uvm.edu Wed Sep 29 03:51:00 1993 Date: Wed, 29 Sep 1993 08:51 EST From: J_BROWN@uvmvax.uvm.edu Subject: answer to request for dihedral angle energy barriers of amines. To: chemistry@ccl.net Message-Id: <01H3IJJSJARK002ITR@uvmvax.uvm.edu> To answer the request for dihedral angle energy barriers: The following reference is a good place to start. It will lead you many other references with respect to dihedral angle energy barriers of MM2 as compaired to variable temp. NMR studies for small amines. Brown, J. H.; Bushweller, C. H.; J. Am. Chem. Soc. 1992, 114, 8153 From jaeric@mtcamm.monsanto.com Wed Sep 29 03:09:47 1993 From: Jon A. Erickson Message-Id: <9309291309.AA03334@mtcamm.monsanto.com> Subject: Re: torsion energies in conjugated systems To: chemistry@ccl.net (OSU Comp. Chem. List) Date: Wed, 29 Sep 93 8:09:47 CDT > Does anyone know a forcefield which includes a term for > torsional energy in a conjugated system? Specifically, I am > interested in rotating the carbonyl in acetophenone out of plane > with the phenyl ring. MOPAC geometry optimization places the > carbonyl in the plane of the ring. Without running a dozen > MOPAC runs, can I get an estimate of what the energy would be > out of the plane? I believe the MM2(or MM3) forcefield would handle this situation quite well. It includes a dihedral driver routine which is automated. This will help you locate the transition state of the rotation, whose energy will give you the barrier. This may have been done for acetophenone, so I would suggest a quick literature search would save you some time. You probably realize this, but from the wording of the question I thought I'd clarify. MOPAC is a semi-empirical molecular orbital method, that is parameterized, but not in the sense of a forcefield, ie. bond, angle, and torsion terms. If you are using MOPAC for a torsion analysis, you can step through the angles by placing a -1 in the column following the dihedral angle of interest, and then put all the steps on a line at the end of the file. If you really want just a quick estimate, just manually set the dihedral to be out of the ring and do a single point energy calculation. Just be aware that this geometry may not be a minima. -- ################################################################ # Jon Erickson e-mail: jaeric@mtcamm.monsanto.com # # Monsanto Company, U3E phone: (314) 694-1511 # # 800 N. Lindbergh Blvd. FAX: (314) 694-1080 # # St. Louis MO, 63167 # # # # What is a magician but a practising theorist? # # -- Obi-Wan Kenobi # ################################################################ From cramer@maroon.tc.umn.edu Wed Sep 29 03:58:54 1993 Message-Id: <0012ca9949e022612@maroon.tc.umn.edu> From: "Christopher J Cramer-1" Subject: What level to stop at To: chemistry@ccl.net Date: Wed, 29 Sep 93 8:58:54 CDT Doug Smith raises an interesting point with respect to the "adequate" level of theory required for a given problem. I would claim that, at least for ab initio calculations, the adequate level is one which has been demonstrated to be converged with respect to increasing basis set size and increasing levels of correlation. Of course, the definition of converged depends on what you want to know -- relative isomeric energies to within 0.1 kcal/mol, vibrational frequencies to within 5 cm(-1), etc. This is expensive in general, but for years theory had a bad name because unconverged levels of theory, which fortuitously agreed with experimental results for some particular system, were then used to make predictions in other systems with disastrous results. Look at the Diels-Alder transition state for butadiene and ethylene. A huge amount of ink has been spilled on this problem, and it's still not absolutely clear what's going on. Now, there are many interesting problems for which convergence clearly can not be obtained economically with modern hardware and software. Obviously we should not just ignore these challenges. However, effort should be made to EXPLICITLY point out how the best available theory may still be inadequate, so that scientists who are not intimately familiar with the ins and outs of theory are not led down some primrose path of what amounts to conjecture. As for other levels of theory, comparison to experiment is the only real way to establish the quality of a level (this applies to ab initio too, of course, my above discussion assumes it implicitly). While the most interesting work often involves moving into an area where experimental data are not available, comparison to similar systems, analysis of other predictions, etc. is helpful. I referee a lot of papers where the theory is simply presented as some sort of burning-bush prophecy. For very specialized journals, this may be appropriate insofar as it adds to the available database of computations which may later be compared to each other and to experiment. It is entirely inappropriate for general interest venues, where our goal should be to illustrate how theory and experiment may be used synergistically. Anyway, that's my sermon, and I'm sticking to it . . . Chris -- Christopher J. Cramer University of Minnesota Department of Chemistry 207 Pleasant St. SE Minneapolis, MN 55455-0431 (612) 624-0859 cramer@maroon.tc.umn.edu From jp_lafemina@ccmail.pnl.gov Wed Sep 29 00:46:00 1993 Date: Wed, 29 Sep 93 07:46 PDT From: John P Lafemina Subject: RE:reviewers and computational resources To: chemistry@ccl.net Message-Id: ---------------------------- Forwarded with Changes --------------------------- From: at -SMTPLink Date: 9/28/93 8:05PM To: John P Lafemina at ~PNL51 Subject: reviewers and computational resources ------------------------------------------------------------------------------- Regarding Doug Smith's comments (below) I have to agree and take them one step further. The key issue is not that computational resources are limited and so one is perhaps justified in not taking the computations to the highest level of theory made possible by hardware and software. The key issue rather, that ALL researchers need to ask relative to a research problem is whether one is performing the study (whether it be computational or experimental) at the APPROPRIATE level to answer the relevant scientific questions. As an example, if the goal is to understand some aspects of the optical excitation spectra of some class of substituted benzenes then I would expect that some semiempirical method such as CNDO/S3 or INDO/S would be the appropriate level of theory. Why waste (yes, waste! given the limited amount of supercomputing resources) some ungodly amount of Cray time doing computations at the highest acronym level to get answers that will not be significantly different that what the semi- empirical theories give. To my mind this issue -- of using the appropriate level of theory for a given research question -- is serious and needs to be addressed by each of us individually.I am interested in what people think about this, and as always. please flame to me personally and not to the net. Cheers! John P. LaFemina Staff Scientist Materials and Interfaces Molecular Science Research Center Pacific Northwest Laboratory d3c876@pnlg.pnl.gov These comments are made without reference to any particular individual or institution. Please do not take offense. In recent weeks I have received, either in my capacity as an author or as an editor, comments on manuscripts and proposals which bother me somewhat. In particular, referees have made statements suggesting that current hardware and software are such that the level of theory in a particular study needs to be increased, i.e. the reviewer believes that the problem was/will be attacked at too low a level of theory. "Certainly," these reviewers state, "the current technology would allow this work to be done at a significantly higher level of theory than the author reports." In some cases I agree with this sentiment. Certain problems require a minimum level of theory. In other cases this is just not necessary. Sure, we can do some molecules and systems using extremely large basis sets and lots of correlation. Or at least our hardware and software are capable of doing that. But do we always have those resources available? If we are using a Supercomputer Center, our resource unit allowance is limited. To run some of these monster calculations would require half a Cray-year in some cases, given the size of the system, the number of calculations to be run, etc. If we use in-house computers, do we really have that much control over shared resources, and will other researchers give up all their access in order to satisfy these reviewers? I consider my research group to be resource rich, given the number, size and type of workstations and the amount of Cray time we have available. And I sometimes may fall prey to this same snobbery, that the calculations should have been done bigger and better. But not everyone (including me, sometimes) is able to do bigger and better. And in many situations (e.g. industrial problems) bigger is NOT better, because it is more expensive, takes more time, and does not substantially improve the answers (i.e. the trends are the same at lower levels of theory, so the direction provided by the calculation doesn't change at higher levels). As scientists, we should always strive to do the best possible job, given the resources available. We should also choose our research problems such that we can do the research right, and (hopefully) get the right answers to our questions, within our resources. But are we correct in saying to others "Do the calculations at MP3/6-311G** rather than MP2/6-31G*, because your computers and software are able to handle it"? Comments and discussion are welcome. Please confine flames to personal responses rather than the net. Doug Douglas A. Smith Assistant Professor of Chemistry and of Medicinal and Biological Chemistry The University of Toledo Toledo, OH 43606-3390 voice 419-537-2116 fax 419-537-4033 email dsmith@uoft02.utoledo.edu --- Administrivia: This message is automatically appended by the mail exploder: CHEMISTRY@ccl.net --- everyone CHEMISTRY-REQUEST@ccl.net --- coordinator OSCPOST@ccl.net send help from chemistry Anon. ftp www.ccl.net CHEMISTRY-SEARCH@ccl.net --- search the archives, read help.search file first --- From mercie@med.cornell.edu Wed Sep 29 07:09:07 1993 Date: Wed, 29 Sep 1993 11:09:07 -0400 (EDT) From: Gustavo Mercier Subject: Re: reviewers and computational resources To: "DR. DOUGLAS A. SMITH, UNIVERSITY OF TOLEDO" Message-Id: On Tue, 28 Sep 1993, DR. DOUGLAS A. SMITH, UNIVERSITY OF TOLEDO wrote: > ... "Certainly," these reviewers state, > "the current technology would allow this work to be done at a significantly > higher level of theory than the author reports." > ... Follow up... I agree with your analysis! But,... Does it means that if we don't have the necessary computer/software power we should not attack a particular problem? I understand that this does not necessarily follow from the reviewers statements, but it certainly could represent the "next step". Obviously (I think!), computers and software resources should not be the sole criteria to decide if a problem is worthy of analysis; otherwise, many of the semiempirical methods would have never been developed! I think these methods are useful and have a role in computational chemistry, even in the age of SUPERcomputers. To present a problem at a much higher level of theory than it requires is a wasteful overkill. I can recognize that benchmarks and "gold standards" have to be defined, but to do full CI every time because "you can" is to concentrate in the computing/numbers rather than the chemistry! Certainly, we may differ in our strengths an preferences as computational chemists, but the end point should be a better understanding of chemistry, not fancier or bigger computations for their own sake. good luck with your rebuttals! gus mercier mercie@cumc.cornell.edu From DURRAN@chem.surrey.ac.uk Sun Sep 29 16:45:23 1993 Message-Id: To: CHEMISTRY@ccl.net From: Michael Organization: Chemistry Department, Uni of Surrey Date: 29 Sep 93 16:45:23 GMT Subject: Need some info....... I've been reading a reference by de Dios and Oldfield, Chem. Phys. Lett. 205(1) , 1993, p108. on methods of computing NMR chemical shielding in large systems. One of their references [41] is as follows : 'P.Pulay, K.Wolinski and J.F.Hinton, The Texas Program, University of Arkansas, Fayetteville, AR (1991)' At first sight this appears as though it is a book, but a lot of checking with our library and bookshop draws a blank. I wonder if anybody could help me i.e, do they know if it is a book or not ?? Thanks for any help Mike From trevor@grserv.wustl.edu Wed Sep 29 04:49:15 1993 Date: Wed, 29 Sep 93 10:49:15 -0600 From: trevor@grserv.wustl.edu (Trevor Creamer) Message-Id: <9309291649.AA13129@giovanni> To: chemistry@ccl.net Subject: RE: reviews / resources Another two-cents worth.... Something that comes to mind over the issue of using higher levels of theory. We should all be asking ourselves if we really _should_ move to higher levels of theory or to more complex calculations. The reason for this is that any calculation will be limited by its weakest part. To quote van Gunsteren and Mark (1992) : "A common error ... is to attempt to improve a basically crude model by performing one aspect of the calculation in a rigorous manner. The accuracy of a model as a whole will remain limited by the crudest approximation or weakest assumption." More complex isn't always better. Cheers, Trevor p.s. A manuscript should never be rejected simply because _you_ can do more complex calculations than the authors can or have. W.F. van Gunsteren and A.E. Mark (1992) J. Mol. Biol. 227, 389-395. ________________________________________________________________________ Trevor P. Creamer Dept. of Biochemistry Email - trevor@grserv.wustl.edu & Molecular Biophysics Phone - (314) 362 4123 Washington University Fax - (314) 362 4115 St. Louis, Missouri 63110 U.S.A. ________________________________________________________________________ From vaisman@gibbs.oit.unc.edu Wed Sep 29 08:58:23 1993 Date: Wed, 29 Sep 93 12:58:23 -0400 From: vaisman@gibbs.oit.unc.edu (Iosif Vaisman) Message-Id: <9309291658.AA23775@gibbs.oit.unc.edu> To: chemistry@ccl.net Subject: NC Symposium on Molecular Modeling: Second announcement and schedule North Carolina Symposium on Molecular Modeling: Integration of Theory and Experiment Research Triangle Park, North Carolina U.S.A. October 21 - 23, 1993 Sponsored by North Carolina Section of American Chemical Society Becton Dickinson Research Center Burroughs Welcome BIOSYM Technologies Molecular Design Limited Molecular Simulations, Inc. MCNC North Carolina Biotechnology Center Tripos Associates, Inc. North Carolina Symposium on Molecular Modeling will take place at MCNC, Research Triangle Park, NC, October 21-23, 1993. The scientific program will emphasize the integrated nature of modern chemical, biochemical, and pharmacological research that requires collaborative efforts of both theoretical and experimental scientists. The program will consist of invited lectures, posters, and software and hardware presentations. An informal picnic at Jordan Lake is planned for attendees. CALL FOR POSTERS Participants are invited to submit poster presentations on any topic related to molecular modeling. One-page abstracts of poster presentations will be included in meeting notes that will be distributed at the symposium. Abstracts must be submitted by October 4. INVITED LECTURES Friday, October 22 8:15 - 9:15 am "Correlations vs. Simulations: Choosing the Appropriate Tool" Garland Marshall, Washington University 9:15 - 10:15 am "Monte Carlo and Molecular Dynamics Simulations with OPLS Forcefield" Julian Tirado-Rives, Yale University 10:30 - 11:30 am "Determining Protein Folds by Inverted and Evolutionary Protein Folding Algorithms" David Eisenberg, University of California at Los Angeles 12:30 - 1:40 pm (CONCERT BROADCAST) "Accuracy of Structure Determination and Structure Prediction: Interplay of Theory and Experiment" Axel Brunger, Yale University Saturday, October 23 8:30 - 9:30 am "Unlimited Expectations, Limited Applications" Gerald Fasman, Brandeis University 9:30 - 10:30 am "Computational Studies on Peptides and Peptoids (Poly N-Substituted Glycines)" David Spellmeyer, Chiron Corporation 10:45 - 11:45 am "A Combined Quantum Mechanical and Molecular Mechanical Approach for Modeling Chemical Reactions in Solution" Jiali Gao, SUNY at Buffalo 1:30 - 2:30 pm "Complexes of HIV Protease with Inhibitors: Modeled and Experimental Structures" Alexander Wlodawer, National Cancer Institute 2:30 - 3:30 pm "Site-Directed Drug Design: Methods and Applications" Richard Ogden, Agouron Pharmaceuticals 4:00 - 5:30 pm Panel Discussion "Accuracy of Molecular Simulations" October 21, 5:00 - 7:30 pm; October 22 and 23, 8:15 am - 5:00 pm Vendors Displays and Demonstrations ORGANIZING COMMITTEE Alexander Tropsha, Chairman, University of North Carolina at Chapel Hill Ken Flurchick, Co-Chairman, MCNC Rebecca McCloskey, Conference Coordinator, MCNC Frank Brown, Glaxo Research Institute Michael Cory, Burroughs Wellcome Co. Jan Hermans, University of North Carolina at Chapel Hill Lee Pedersen, University of North Carolina at Chapel Hill Iosif Vaisman, University of North Carolina at Chapel Hill TRAVEL AND ACCOMMODATIONS MCNC is located in Research Triangle Park, one mile north of I-40 and five miles from Raleigh-Durham International Airport. The symposium hotel is the Holiday Inn in Research Triangle Park. The hotel rates are $72 plus tax per night. Please make your reservation directly with the hotel by calling 919-941-6000. Indicate that the registration is for the ACS Symposium. The hotel registration deadline is October 1. After this deadline, reservations will be accepted depending on availability. Rental cars are available at the airport. For additional administrative information, contact Rebecca McCloskey at 919-248-1841. REGISTRATION Complete the attached registration form and return with payment by October 10 to MCNC, P.O. Box 12889, Research Triangle Park, NC 27709 Attn: R. G. McCloskey. Only checks and money orders will be accepted (no credit cards). Make checks payable to the ACS Symposium. Payment must be included with registrations. For further technical information, call Alex Tropsha at 919-966-2955 (e-mail tropsha@gibbs.oit.unc.edu) or Ken Flurchick at 919-248-1121 (e-mail kenf@ncsc.org). For administrative information, call Rebecca McCloskey at 919-248-1841 or send e-mail to gebuhr@mcnc.org. REGISTRATION FEES Industrial participants $170 Academia and Government $ 65 Post-doctorates $ 35 Graduate students $ 25 Registration fees include the reception, the picnic dinner at Jordan Lake, two lunches, refreshment breaks, and meeting materials. REGISTRATION FORM Symposium on Molecular Modeling: Integration of Theory and Experiment Registration is limited and will be accepted on a first-come, first-served basis. Make checks payable to the ACS Symposium. Registrations will not be accepted without payment. Send your registration to the following address: MCNC P.O. Box 12889 3021 Cornwallis Road Research Triangle Park, NC 27709 Attn: R. G. McCloskey Name Position/Title Affiliation Address City State, Zip Phone Fax Email __I will be presenting a poster and will require 30"x40" posterboard to mount my presentation. Indicate dietary restrictions ___________________________________________ From C867BUC%SEMOVM.BITNET@phem3.acs.ohio-state.edu Wed Sep 29 08:39:34 1993 Date: Wed, 29 Sep 1993 13:39:34 -0500 (CDT) From: "Anthony J. Duben" Subject: reviewers and resources -- D. Smith's comment To: chemistry@ccl.net Message-Id: <29SEP93.14752582.0083.MUSIC@SEMOVM> I have to add my "Amen" to Doug Smith's observation. Just because a computational resource may be available to certain individuals (i.e., the reviewers), it may not be generally available -- not only does this mean computer time on a Cray, but also high performance workstations with expensive software packages. Many smaller institutions without graduate programs (such as mine) would treat a person with an Indigo on his disk as a researcher with high power computing at his disposal. Snobbish comments (which I have received myself) do not speak well of the choice of reviewers. Are they professionally open-minded or are they competent to do the job? The question is: has the submitter posed an interesting problem and has something useful and interesting been said about it? If the research had been done on a PC, so what? A lot of number crunching goes on under the guise of doing something worthwhile, but all that it contributes to is global warming. About the only response that a person who has received such comments can make is to raise lots of Hell with the editor of the journal who makes the reviewer assignments. Tony Duben ********************************************************************** Anthony J. Duben Southeast Missouri State University Computer Science Department, Mail Stop 6800 1 University Plaza Cape Girardeau MO 63701-4799 voice: (314) 651-2194 FAX: (314) 651-2791 bitnet: C867BUC@SEMOVM internet: C867BUC@SEMOVM.SEMO.EDU "No good deed ever goes unpunished" ********************************************************************** From fredvc@esvax.dnet.dupont.com Wed Sep 29 12:03:53 1993 Date: Wed, 29 Sep 93 16:03:53 -0400 Message-Id: <9309292003.AA23087@esds01.es.dupont.com> From: fredvc@esvax.dnet.dupont.com To: chem@ccl.net Subject: REVIEWS, RESOURCES, AND EDITORS I found Doug Smith's comments interesting!! This phenomenon, the pressing for higher-level calculations, appears to me (as a former journal editor) to be the latest version of a rather standard reviewers' ploy. If one is not comfortable with the content/presentation in a paper, a general recommendation to do more (or "higher quality") X puts the burden of proof on the author. The editor has a responsibility for maintaining balance/fairness in such cases. The reviewer needs to be challenged to make a case for the additional work, e.g., "If these calculations are redone at the MP3/6-311G** level, what specific *significant* insights do you anticipate that are likely to be missed by the current (MP2/6-31G*) report?" This requires a more "hands-on" approach than is customary. We want the science to be significant, yet we don't want to compel people to *needlessly* expend computer cycles (or spectrometer time, or time at the bench making compounds, etc.) It's a tough call, one that makes editing challenging,... and more than a little frustrating!! I guess you could say that if you are doing your job the reviewers and the authors will stop speaking to you for at least a month!! ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ FREDERIC A. VAN-CATLEDGE Scientific Computing Division || Office: (302) 695-1187 or 529-2076 Central Research & Development Dept. || The DuPont Company || FAX: (302) 695-9658 P. O. Box 80320 || Wilmington DE 19880-0320 || Internet: fredvc@esvax.dnet.dupont.com -------------------------------------------------------------------------------- Opinions expressed in this electronic message should ***> NOT <*** be taken to represent the official position(s) of the DuPont Company. *****> ANY OPINIONS EXPRESSED ARE THE PERSONAL VIEWS OF THE AUTHOR ONLY. <***** ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ From stoutepf@chemsci1.es.dupont.com Wed Sep 29 12:30:59 1993 Message-Id: <9309292129.AA16758@chemsci1.es.dupont.com. chemsci1 chemsci1.es.dupont.com> Date: Wed, 29 Sep 1993 17:30:59 -0500 To: chemistry@ccl.net, dibug@comp.bioz.unibas.ch From: stoutepf@chemsci1.es.dupont.com (Pieter Stouten) Subject: Torsional energy in conjugated systems In some recent postings to the Computational Chemistry List the issue of force fields for conjugated pi-systems was brought up. Marty Gallagher wrote: > Does anyone know a forcefield which includes a term for > torsional energy in a conjugated system? > Conjugated pi-systems constitute one of the larger issues in the development of force fields that describe macromolecule-drug interactions adequately. Efforts generally seem aimed at sort of ad hoc development of parameters for a small number of closely related compounds. Often times these will not be transferable and consistent with parameters that have been developed in the same vein for other compounds containing the same functional groups. We are in desparate need of a concerted effort towards a consistent treatment of conjugated pi-systems. I sincerely hope this will be a (the ?) main focus of the Biosym Potential Energy Forcefield Consortium over the next years. I also hope that more institutions will join the consortium so that the development of the force field can be given some more momentum. Pieter Stouten, Senior Research Scientist || Computer Aided Drug Design Group || The Du Pont Merck Pharmaceutical Company || Adventures get spoiled P.O. Box 80353, Wilmington, DE 19880-0353 || by being reduced to data Phone: +1 (302) 695 3515 || -- Fax: +1 (302) 695 2813 || Poul Anderson ARA/Fax: +1 (302) 695 4324 || E-mail: stoutepf@chemsci1.es.dupont.com || From FR042008@YSUB.YSU.EDU Wed Sep 29 18:34:36 1993 Date: Wed, 29 Sep 1993 22:34:36 -0400 (EDT) From: Janet Del Bene Subject: Response to Doug Smith To: chemistry@ccl.net Message-Id: <01H3JCCL3MAA8X3715@phem3.acs.ohio-state.edu> Doug Smith has raised a very important point, which is also a complex one. It seems to me that "this is all that I can afford to do" is not a justification for scientific work when there is evidence in the literature that the proposed level of theory is not adequate for the problem under investigation. To illustrate. If an experimentalist has an instrument which can measure events on a time scale of 10(-8) seconds, but he wishes to measure an event which occurs in 10(-10)) seconds, should he use that instrument to make the measurement? I do not believe that practicality is a justfication in this case. So, what is the answer? In my opinion there are two options: 1) reformulate the problem, so that what is to be investigated can be done at an appropriate level of theory; or 2) carefully investigate closely related systems so that meaningful trends can be extracted, and there is a good chance for a systematic cancellation of errors. Some may consider this a "hard-line" approach, but if what we as theoretical, computational chemists do is to have lasting value, then in my opinion, this is the way to go. Janet E. Del Bene