From hughc@extro.ucc.su.oz.au Wed Feb 22 00:51:49 1995 Received: from extra.ucc.su.OZ.AU for hughc@extro.ucc.su.oz.au by www.ccl.net (8.6.9/930601.1506) id AAA04258; Wed, 22 Feb 1995 00:28:12 -0500 Received: from hugh (hugh.pharmacol.su.OZ.AU [129.78.41.50]) by extra.ucc.su.OZ.AU (8.6.9/8.6.9) with SMTP id QAA24053 for ; Wed, 22 Feb 1995 16:28:03 +1100 Message-Id: <199502220528.QAA24053@extra.ucc.su.OZ.AU> X-Sender: hughc@postbox.su.edu.au Mime-Version: 1.0 Content-Type: text/plain; charset="us-ascii" Date: Wed, 22 Feb 1995 16:27:01 +1000 To: chemistry@ccl.net From: hughc@extro.ucc.su.OZ.AU (Hugh Capper) Subject: 2-D structures for publication X-Mailer: Dear CCLers, I am looking for advice on different Windows 3.1 compatible 2-D structure editors. What is available out there? Thanks in advance, Best wishes, Hugh Capper From rosas@irisdav.chem.vt.edu Wed Feb 22 00:53:20 1995 Received: from irisdav.chem.vt.edu for rosas@irisdav.chem.vt.edu by www.ccl.net (8.6.9/930601.1506) id XAA03870; Tue, 21 Feb 1995 23:54:47 -0500 Received: by irisdav.chem.vt.edu (931110.SGI/931108.SGI.AUTO.ANONFTP) for chemistry@ccl.net id AA03101; Tue, 21 Feb 95 23:53:19 -0800 From: "Victor M. Rosas Garcia" Message-Id: <9502212353.ZM3099@irisdav.chem.vt.edu> Date: Tue, 21 Feb 1995 23:53:15 -0800 X-Mailer: Z-Mail (3.1.0 22feb94 MediaMail) To: chemistry@ccl.net Subject: CCL:TELLING IF TWO CONFORMERS ARE IDENTICAL Content-Type: text/plain; charset=us-ascii Mime-Version: 1.0 In an answer to Dongchul Lim about how one can tell if two conformers are the same, Errol Lewars recommends calculation of the total internuclear repulsion. Would that work in the case of conformational enantiomers? Victor M. Rosas Garcia rosas@irisdav.chem.vt.edu From nobes@theor.ch.cam.ac.uk Wed Feb 22 01:51:50 1995 Received: from ppsw3.cam.ac.uk for nobes@theor.ch.cam.ac.uk by www.ccl.net (8.6.9/930601.1506) id BAA04751; Wed, 22 Feb 1995 01:24:22 -0500 Received: from theor.ch.cam.ac.uk (actually gmos.ch.cam.ac.uk) by mauve.csi.cam.ac.uk with SMTP-CAM (PP-7.1) as ppsw.cam.ac.uk; Wed, 22 Feb 1995 06:23:11 +0000 Received: by theor.ch.cam.ac.uk (931110.SGI/930416.SGI) for @ppsw.cam.ac.uk:chemistry@ccl.net id AA20798; Wed, 22 Feb 95 06:24:29 GMT From: nobes@theor.ch.cam.ac.uk (Ross Nobes) Message-Id: <9502220624.AA20798@theor.ch.cam.ac.uk> Subject: Reminder - Conference Registration To: chemistry@ccl.net Date: Wed, 22 Feb 1995 06:24:28 +0000 (GMT) X-Mailer: ELM [version 2.4 PL23] Content-Type: text Content-Length: 2239 ***** A REMINDER - EARLY REGISTRATION IS DUE BY 1 MARCH ***** Molecular Quantum Mechanics: Methods and Applications An International Conference in Memory of Samuel Francis Boys and in Honour of Isaiah Shavitt 3-7 September 1995 St Catharine's College University of Cambridge Cambridge, England Co-Chairmen: N.C. Handy (Cambridge) and H.F. Schaefer (Georgia) Organiser: R.H. Nobes (Canberra and Cambridge) This major international conference celebrates forty years of ab initio polyatomic quantum chemistry, marking the 40th anniversary of the submission for publication of the paper 'Automatic Fundamental Calculations of Molecular Structure' by S.F. Boys, G.B. Cook, C.M. Reeves and I. Shavitt. The conference will consist of six historical lectures, 30 plenary lectures (covering modern methods and applications in ab initio quantum chemistry) and three contributed poster sessions. Proceedings of the conference will be published as a special issue of the Journal of Physical Chemistry. The registration form and details can be retrieved from CCL archives via e-mail, ftp, gopher and WWW as: 1) e-mail: send a message: select chemistry limit 300kb get info/conferences quit to MAILSERV@ccl.net 2) ftp: ftp www.ccl.net Name: anonymous Password: Your_e-mail_address ftp> cd pub/chemistry/info ftp> get conferences ftp> quit 3) gopher: gopher www.ccl.net 73 info conferences 95.09.03 4) Word Wide Web: http://www.ccl.net/~ccl/info.html choose Conferences 95.09.03 -- +---------------------------------------------------------------------+ | Ross Nobes | | Department of Chemistry Phone: + 44 223 336384 | | University of Cambridge Fax: + 44 223 336362 | | Lensfield Road | | Cambridge CB2 1EW, UK E-mail: nobes@theor.ch.cam.ac.uk | +---------------------------------------------------------------------+ From san@mbu.iisc.ernet.in Wed Feb 22 02:51:50 1995 Received: from sangam.ncst.ernet.in for san@mbu.iisc.ernet.in by www.ccl.net (8.6.9/930601.1506) id BAA04957; Wed, 22 Feb 1995 01:56:26 -0500 From: Received: from soochak.ncst.ernet.in (soochak.ncst.ernet.in [144.16.11.100]) by sangam.ncst.ernet.in (8.6.8.1/8.6.6) with ESMTP id MAA17113 for ; Wed, 22 Feb 1995 12:26:01 +0530 Received: from iisc.ernet.in (iisc.iisc.ernet.in [144.16.64.3]) by soochak.ncst.ernet.in (8.6.8.1/8.6.5) with SMTP id MAA07306 for ; Wed, 22 Feb 1995 12:23:06 +0530 Received: from vigyan.UUCP by iisc.ernet.in (ERNET-IISc/SMI-4.1) id AA24296; Wed, 22 Feb 95 12:31:00+0530 Date: Wed, 22 Feb 95 12:31:00+0530 Message-Id: <9502220701.AA24296@iisc.ernet.in> Received: by vigyan.iisc.ernet.in (smail2.3) id AA04871; 22 Feb 95 11:33:54 EST (Wed) To: vigyan!chemistry@ccl.net Subject: conformational isomers >From: Dongchul Lim >Subject: CCL:conformational isomers >Status: R >Is there a simple way of testing if two given conformational isomers >are equivalent? >E.g., how can you know the gauche (+) conformer of n-butane is >equivalent to the gauche (-) conformer? >My idea is >1) superimpose the two conformers. >2) if they are not superimposed, superimpose the one conformer > and the mirror image of the other. > >Any ideas? >-D.L. dear D.L. , I think one way to test the conformational equivalence esp. for small structures like n-butane is to calculate or measure the energies of the two isomers. For example, in case of n-butane both g+ and g- have almost equal energies i.e. both of them are almost equally stable while trans isomer has lower energy than any of the two and is much more stable than any of the two. I restrict myself to recomend its usage with small organic molecules with simple geometries only. for further disscussion on the matter please refer to organic chemistry text book by Morrison and Boyd. yours' cordially sandeep kumar san@mbu.iisc.ernet.in P.S. I shall be grateful to you if you summarize what you find. From thys@schs.uia.ac.be Wed Feb 22 02:56:33 1995 Received: from sch2.uia.ac.be for thys@schs.uia.ac.be by www.ccl.net (8.6.9/930601.1506) id CAA05309; Wed, 22 Feb 1995 02:38:47 -0500 Received: from localhost by sch2.uia.ac.be (8.6.4/Ultrix3.0-C) id IAA15055; Wed, 22 Feb 1995 08:36:57 +0100 Date: Wed, 22 Feb 1995 08:36:53 +0100 (MET) From: Gerd Thys X-Sender: thys@sch2.uia.ac.be To: CCL Subject: Semi-empirical methods + CI Message-ID: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Dear all, I'm using PM3 and AM1 followed by MECI (as implemented in MOPAC) to calculate excitation-energies of a series of (large) closed-shell organic molecules. As a test, I did some MECI calculation including 3 up to 8 orbitals to correct for the correlation energy (In MOPAC: MECI C.I.=3 to C.I.=8). I was told to be careful no to add too much orbitals in de MECI-calculation, since part of the correction for the correlation energy is already included in the AM1/PM3 (and any other) parameterization. Adding too much orbitals would overestimate the excitation energy. In some cases, the first singlet-singlet excitation energy at a given number of orbitals results in the following: PM3: C.I.=5 E= 3.571 eV (347 nm) C.I.=6 E= 3.624 eV (342 nm) C.I.=7 E= 3.472 eV (366 nm) C.I.=8 E= 3.436 eV (361 nm) In other words, at a given # of orbitals (in this case C.I.=6), the energy reaches a maximum. Normally I would expect energy to lower with adding orbitals (and most of the time this is the case). Now my question to you all: Is this 'going through a maximum' an effect of the overcompensation of the correlation energy? Are there any other effects (depending on the electronic structure of the molecule)? Thanks for your reaction, Gerd ---------------------------------------------------------------------------- Gerd Thys Ph.D. Student Structural Chemistry Group University of Antwerp (UIA) Universiteitsplein 1 E-mail: thys@uia.ua.ac.be B-2610 wilrijk URL: http://www.uia.ac.be/u/thys/index.html BELGIUM ---------------------------------------------------------------------------- From adit@extreme.chem.rpi.edu Wed Feb 22 08:51:53 1995 Received: from rpi.edu for adit@extreme.chem.rpi.edu by www.ccl.net (8.6.9/930601.1506) id IAA08167; Wed, 22 Feb 1995 08:19:57 -0500 Received: from quant.chem.rpi.edu by rpi.edu (4.1/SMHUB41); id AA15344; Wed, 22 Feb 95 08:19:15 EST for chemistry@ccl.net Received: from extreme.chem.rpi.edu by quant.chem.rpi.edu (4.1/ST26); id AA01766 for chemistry@ccl.net; Wed, 22 Feb 95 08:15:58 EST Received: by extreme.chem.rpi.edu (920330.SGI/921111.SGI.AUTO) for @quant.chem.rpi.edu:chemistry@ccl.net id AA05253; Wed, 22 Feb 95 08:18:56 -0500 Date: Wed, 22 Feb 95 08:18:56 -0500 From: adit@extreme.chem.rpi.edu (Adi Treasurywala) Message-Id: <9502221318.AA05253@extreme.chem.rpi.edu> To: chemistry@ccl.net Subject: Legal Question. Folks, In a recent discussion here it was pointed that the VERY SEARCHING of the genbank collection of sequences through the Internet, for example, (or any other collection for that matter) constituted a "public disclosure" of that sequence and this had some consequences regarding getting a patent later on. I am looking for some advice on the correctness of this statement from anyone with knowledge in this area. It seems to me to have some serious consequences if true, to all such uses of the Internet. Adi T. From valery-g@dcl.co.il Wed Feb 22 09:00:00 1995 Received: from datasrv.co.il for valery-g@dcl.co.il by www.ccl.net (8.6.9/930601.1506) id IAA08636; Wed, 22 Feb 1995 08:45:49 -0500 Received: from dclpc (dclgate.dcl.co.il) by datasrv.co.il with SMTP id AA00359 (5.65c/IDA-1.4.4 for ); Wed, 22 Feb 1995 15:45:40 +0200 Received: from indigo2.dcl.co.il by dclpc (5.65/SMI-4.1) id AA18015; Wed, 22 Feb 95 15:43:28 GMT Received: by indigo2.dcl.co.il (940816.SGI.8.6.9/SMI-4.1) id PAA20160; Wed, 22 Feb 1995 15:48:33 +0200 Date: Wed, 22 Feb 1995 15:48:33 +0200 From: valery-g@dcl.co.il (Dr. Golender Valery) Message-Id: <199502221348.PAA20160@indigo2.dcl.co.il> To: chemistry@ccl.net Subject: CCL:TELLING IF TWO CONFORMERS ARE IDENTICAL Cc: valery@actcom.co.il Dongchul Lim asked how one can tell if two conformers are the same. I already saw some responses on the net advising to solve the problem from the molecular modeling point of view. In fact, there exist a strict mathematical formulation of this problem called isomorphism of 3D objects. It is a common problem arising in a number of applications including 3D database search, ligand design, spanning of conformational space and etc. A number of different algorithms and programs were proposed to solve this problem. Simple superposition suggested in the original posting is not working because of molecular symmetry. We recently developed an efficient algorithm incorporated into the conformer clustering utility of Apex-3D activity prediction system marketed by Biosym. I can provide more detailed information for ccl-netters interested in this functionality. Good luck to all isomer hunters, Valery Golender, Ph.D. DCL Systems International Ltd 20 Galgalei Haplada St. POB 544 Herzlia 46105 ISRAEL Tel: + 972-9-584-684 Fax: + 972-9-543-917 E-mail: valery-g@dcl.co.il, valery@actcom.co.il From pbays@saintmarys.edu Wed Feb 22 09:52:10 1995 Received: from jade.saintmarys.edu for pbays@saintmarys.edu by www.ccl.net (8.6.9/930601.1506) id JAA09837; Wed, 22 Feb 1995 09:34:05 -0500 Received: by jade.saintmarys.edu (1.37.109.11/16.2) id AA184314016; Wed, 22 Feb 1995 09:40:16 -0500 Date: Wed, 22 Feb 1995 09:40:15 -0500 (EST) From: Phil Bays To: Chemistry Subject: C on an SGI R8000 Message-Id: Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Here is a question about development software as it relates to computaitonal chemistry. There are many sources of good free software for unix boxes in various ftp sites about which most of us are aware. That software, for a variety of good reasons, is availble is source code format (both so that users can modify for their own purposes, and so that compilation can be machine and locally specific.) My problem is that SGI does not supply a c compiler with their hardware when purchased. You have to buy the separate package. I currently have an R8000 and as far as I know, gcc has not yet been ported to that platform. I talked with my local SGI rep yesterday and was told that the list price for C is $1500 (not too bad) and the yearly maintenence contract lists at $1440 (absurd!). Here is the question: Does this pricing represent the standard approach by vendors? Have any of you used the current version of C on the R8000 and is it stable. I would hate to sepnd the purchase price without the maintenece and then find the next week that the code was buggy and needed updated. Phil Bays pbays@saintmarys.edu bays@chem.saintmarys.edu From jaw@camsci.com Wed Feb 22 10:52:19 1995 Received: from camsci.com for jaw@camsci.com by www.ccl.net (8.6.9/930601.1506) id KAA11702; Wed, 22 Feb 1995 10:49:51 -0500 Received: from [149.53.1.43] (technetium.camsci.com) by camsci.com (4.1/3.1.090690-Cambridge Scientific Computing) id AA09758; Wed, 22 Feb 95 10:49:36 EST Message-Id: <9502221549.AA09758@camsci.com> X-Sender: jaw@helium.camsci.com Mime-Version: 1.0 Content-Type: text/plain; charset="us-ascii" Date: Wed, 22 Feb 1995 10:51:02 -0500 To: hughc@extro.ucc.su.OZ.AU (Hugh Capper), CHEMISTRY@ccl.net From: jaw@camsci.com (Joel Wolff) Subject: Re: CCL:2-D structures for publication >Dear CCLers, >I am looking for advice on different Windows 3.1 compatible 2-D structure >editors. What is available out there? >Thanks in advance, >Best wishes, >Hugh Capper > > >-------This is added Automatically by the Software-------- >-- Original Sender Envelope Address: hughc@extro.ucc.su.oz.au >-- Original Sender From: Address: hughc@extro.ucc.su.OZ.AU >CHEMISTRY@ccl.net -- everyone | CHEMISTRY-REQUEST@ccl.net -- coordinator >MAILSERV@ccl.net: HELP CHEMISTRY | Gopher: www.ccl.net 73 >Anon. ftp www.ccl.net | CHEMISTRY-SEARCH@ccl.net -- archive search >http://www.ccl.net/chemistry.html | for info send: HELP SEARCH to MAILSERV Hugh, If you would like information about ChemDraw for Windows, we can send you some information, or you can get the information directly from our WWW or ftp sites. Joel A. Wolff, Ph.D. Customer Service Manager CambridgeSoft Corporation 875 Massachusetts Avenue Cambridge, MA 02139 Phone: (800)315-7300 or (617) 491-2200 Fax: (617) 491-7203 Compuserve: 76070,615 Internet: info@camsci.com http://www.camsci.com ftp://ftp.camsci.com From polowin@hyper.hyper.com Wed Feb 22 11:06:30 1995 Received: from quartz.sentex.net for polowin@hyper.hyper.com by www.ccl.net (8.6.9/930601.1506) id KAA11238; Wed, 22 Feb 1995 10:31:45 -0500 Received: from hyper.hyper.com (Uhyper@localhost) by quartz.sentex.net (8.6.5/8.6.9) with UUCP id KAA11802 for ccl.net!CHEMISTRY; Wed, 22 Feb 1995 10:27:42 -0500 Received: by hyper.hyper.com.hyper.com (920330.SGI/890607.SGI) (for ccl.net!CHEMISTRY) id AA14832; Wed, 22 Feb 95 10:29:54 -0500 Date: Wed, 22 Feb 95 10:29:54 -0500 From: polowin@hyper.hyper.com (Joel Polowin) Message-Id: <9502221529.AA14832@hyper.hyper.com.hyper.com> To: CHEMISTRY@ccl.net Subject: Re: CCL:TELLING IF TWO CONFORMERS ARE IDENTICAL > From: "E. Lewars" > Subject: CCL:TELLING IF TWO CONFORMERS ARE IDENTICAL > > Dongchul Lim asked how one can tell if two conformers are the same. This is > a special case of how to tell if two isomers are really the same species. > It seems to me a simple approach is (after looking to see that they are > not obviously different) to have your program (MOPAC, GAUSSIAN etc) > calculate the total internuclear repulsions. Two species that look the same > and have the same internuclear repulsions (to 6 or more decimals--Hartrees) > are, I would think, extremely unlikely not to be the same. Many comp. > chem programs calculate internucl. repulsions; if a check job wn't give > that number, then ask for a single-point calc. using a fast method like > a semiempirical routine. The actual internuclear repulsin calc. is > trivial. I don't think the situation is quite so simple -- possibly depending on what is meant by conformers being "the same". If I have a large structure and alter a torsional angle in the middle by a fraction of a degree, it's probably still "the same structure". If the structure was energy- optimized before, it's very likely that trying to optimize it again won't do much to change it back unless there are other steric effects. But the atoms at the ends of this large structure will probably move a *lot* as the result of that tiny bend in the middle, and the internuclear repulsions are likely to change significantly too. Maybe only a little, or maybe some other local minimum would be found, but I don't think the internuclear repulsions would likely be the same to 6 or more decimals. I think that the matter depends critically on: What sort of structures are you trying to compare, and what do you mean by "the same"? Regards, Joel ------------ Joel Polowin, Ph.D. Manager, Scientific Support Email to: polowin@hyper.com Hypercube Inc, 7-419 Phillip St, Waterloo, Ont, Canada N2L 3X2 (519)725-4040 Info requests to: info@hyper.com Support questions to: support@hyper.com Email group: Send "subscribe hyperchem" to hyperchem-request@hyper.com From garciae@ucsub.colorado.edu Wed Feb 22 12:52:03 1995 Received: from ucsub.colorado.edu for garciae@ucsub.colorado.edu by www.ccl.net (8.6.9/930601.1506) id MAA14859; Wed, 22 Feb 1995 12:26:54 -0500 Received: (from garciae@localhost) by ucsub.colorado.edu (8.6.9/8.6.9/CNS-3.5) id KAA22079; Wed, 22 Feb 1995 10:26:52 -0700 Date: Wed, 22 Feb 1995 10:26:51 -0700 (MST) From: Garcia Edgardo To: chemistry@ccl.net Subject: CCL: Conformational Isomers Message-ID: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII About the conf. isomers question of Dongchul Lim, my opinion is that first we should ask if we want to compare IDENTICAL or EQUIVALENT isomers (concerning energy for example). In the first case a simple superpossition will probably work. In the second we can make a non-bonding energy calculation and compare the energies or compare the distance matrix of the structures (or some kind of invariant of them) within some allowed range of values. Edgardo Garcia Cristol Chem. & Biochem. Univ. of Colorado BOULDER CO USA From kappler@SECS.UCSC.EDU Wed Feb 22 15:52:07 1995 Received: from MOLENG.UCSC.EDU for kappler@SECS.UCSC.EDU by www.ccl.net (8.6.9/930601.1506) id PAA18491; Wed, 22 Feb 1995 15:21:28 -0500 Received: by SECS.UCSC.EDU (MX V3.1C) id 13861; Wed, 22 Feb 1995 12:20:41 PST Date: Wed, 22 Feb 1995 12:20:36 PST From: Mick Kappler To: chemistry@ccl.net CC: kappler@SECS.UCSC.EDU Message-ID: <0098C5D7.295A793B.13861@SECS.UCSC.EDU> Subject: conformational isomers On Tue, 21 Feb 95 4:08:12 EST, Dongchul Lim wrote: > Is there a simple way of testing if two given conformational isomers > are equivalent? Yes. The Stereochemical Extended Morgan Algorithm (SEMA) developed by Wipke and Dyott provides a stereochemical canonical name. Comparison of the structure SEMA names is straight forward. Mick Kappler Molecular Engineering Laboratory W. Todd Wipke Group Univ. of California, Santa Cruz From elewars@alchemy.chem.utoronto.ca Wed Feb 22 17:52:04 1995 Received: from alchemy.chem.utoronto.ca for elewars@alchemy.chem.utoronto.ca by www.ccl.net (8.6.9/930601.1506) id RAA21289; Wed, 22 Feb 1995 17:10:30 -0500 Received: (from elewars@localhost) by alchemy.chem.utoronto.ca (8.6.9/8.6.9) id RAA20229 for chemistry@ccl.net; Wed, 22 Feb 1995 17:10:28 -0500 Date: Wed, 22 Feb 1995 17:10:28 -0500 From: "E. Lewars" Message-Id: <199502222210.RAA20229@alchemy.chem.utoronto.ca> To: chemistry@ccl.net Subject: COMPARING ISOMERS When I suggested using the internuclear repulsion E to check if two isomers are identical, I should have pointed out that enantiomers have precisely the same energies--internuclear, electronic, etc (in the absence of a chiral perturbation; physicists may quibbl, too, that the negation of parity by the weak nuclear force causes a miniscule difference in enantiomer E's). Joel Polowin of HyperChem pointed out that as a practical matter identity isn't an all-or-nothing phenomenon: how similar do two species have to be for a chemist to call them the same thing? As several people said, there are sophisticated algorithms for matching up two molecules and looking at, e.g., RMS differences in geometric parameters. I think the widely- used MM program PCModel can do something like this; one or two other programs were mentioned. Joel's idea about a small tweak in one part of a molecule causing a ratcheting effect that's amplified elsewhere (cf. allosteric effects in enzymes?) is interesting. Errol Lewars =============================== Regarding internucl rep.--one could calc it for some test cases, alter these geometries slightly, and see if it might be useful for the problem at hand. =============== From marvin@iris131.biosym.com Wed Feb 22 17:54:29 1995 Received: from bioc1.biosym.com for marvin@iris131.biosym.com by www.ccl.net (8.6.9/930601.1506) id RAA21952; Wed, 22 Feb 1995 17:48:15 -0500 Received: from iris131.biosym.com by bioc1.biosym.com (5.64/0.0) id AA27537; Wed, 22 Feb 95 14:48:34 -0800 Received: by iris131.biosym.com (940816.SGI.8.6.9/930416.SGI) for CHEMISTRY@ccl.net id OAA02375; Wed, 22 Feb 1995 14:47:42 -0800 Date: Wed, 22 Feb 1995 14:47:42 -0800 From: marvin@biosym.com (Marvin Waldman) Message-Id: <199502222247.OAA02375@iris131.biosym.com> To: CHEMISTRY@ccl.net Subject: RE: conformational isomers On Tue, 21 Feb 95 4:08:12 EST, Dongchul Lim wrote: > Is there a simple way of testing if two given conformational isomers > are equivalent? This is, in fact, quite a difficult and subtle question. The SEMA algorithm which Mick Sappler proposed can be used to detect if two CONFIGURATIONAL isomers are equivalent (ie. they have the same or different stereochemistry). However, it will not detect if the same configurational isomers are equivalent or not in a CONFORMATIONAL sense. SEMA cannot detect the difference between the gauche and trans forms of n-butane. These are CONFORMATIONAL isomers. The issue of the equivalence of two conformations is further complicated by the problem of topological symmetry. This makes an RMS comparison of atoms problematic for detecting equivalent conformations. For example, if I do an RMS comparison of corresponding atoms between two conformers in which the hydrogens of a methyl group are rotated by 120 degrees, I will detect an RMS difference because I am now comparing the wrong set of atoms. One needs to compare all combinations of topologically equivalent atoms in the molecule to see if they have a (virtually) zero RMS. If one proposes to do an RMS comparison of heavy atoms only, then you only need to replace the methyl group with a t-butyl group, and the problem remains. If one proposes to compare only energies (and not RMS), then, of course, the symmetry will be correctly handled for the energy, and you only need to worry about the somewhat unlikely case of two different conformers having (almost?) the same energy. Since these conformers are likely to come from some energy optimization procedure, roundoff error and tolerances used for the minimization implies that one needs to use some kind of tolerance in comparing energies, which always leads to the (remote?) possibility that nearly equal energies may not correspond to the same conformer. The larger the molecule and the more conformational flexibility (and therefore conformers) it has, the more likely that this somewhat theoretical problem may manifest itself in a real example. The ideal/correct solution would be to compare both the energy as well as all combinations of RMS comparisons of topologically equivalent atoms until the RMS difference found for a given comparison pair fell below some threshold. I am not aware of a software package that has actually implemented such an algorithm, and would be very interested to hear about one that does. So, the bottom line answer to the question, is: No, I don't think there is a SIMPLE way to do this. Marvin Waldman, Ph.D. Manager, Rational Drug Design Biosym Technologies, Inc. e-mail: marvin@biosym.com From cbas25@vms.strath.ac.uk Wed Feb 22 20:52:00 1995 Received: from harris.cc.strath.ac.uk for cbas25@vms.strath.ac.uk by www.ccl.net (8.6.9/930601.1506) id UAA24139; Wed, 22 Feb 1995 20:48:33 -0500 Received: from vaxb.cc.strath.ac.uk (actually host vaxb.strath.ac.uk) by harris with SMTP (PP); Thu, 23 Feb 1995 01:47:54 +0000 Received: by vms.strath.ac.uk (MX V4.1 VAX) id 1; Thu, 23 Feb 1995 01:48:16 EST Date: Thu, 23 Feb 1995 01:47:29 EST From: "CBAS25 ::P_BLADON ::CBAS25" To: chemistry@ccl.net Message-ID: <0098C647.E21ABB00.1@vms.strath.ac.uk> Subject: Conformational Isomers Dear Dongchul Lim, With regard to the conparisons of conformers. There are several points to consider. (1) If the problem involves small molecules like butane where the number of stable conformers is known, then simply superimposing the "unknown" structure on each of the "known" conformers in turn will give an answer. The rms deviation of atom positions or some other figure of merit will afford an answer even when an exact match is not achieved. (2) If the structures are more complex, perhaps involving large membered rings, then the number of conformers could be large. But suppose that you have a set of such structures, and wish to test which of them your "unknown" most resembles. You would still get an answer. If the "unknown" were a crystal structure and the "knowns" derived >from a conformer generating program, you would not expect a good match necessarily. What you could do then is to take the pair of best matched structures and refine them with your favourite MM or MO package, and see if they both decend into the same energy well. (3) To do the matching you could use atom to atom matching, or alternatively use the icosahedral matching algorithm in programs like COMPARISONS or CORRELATE. The first of these programs will match an "unknown" against a series of "unknowns", while the second would allow the correlation of a whole series of conformers. The matching of mirror-image forms is taken care of. Both programs are available from QCPE as part of the INTERCHEM package. Yours sincerely Peter Bladon cbas25@vaxa.strath.ac.uk Phone/Fax +44-141-776-1718 From jeremy@med.su.oz.au Wed Feb 22 22:52:10 1995 Received: from blackburn.med.su.oz.au for jeremy@med.su.oz.au by www.ccl.net (8.6.9/930601.1506) id WAA25070; Wed, 22 Feb 1995 22:19:16 -0500 Received: (jeremy@localhost) by blackburn.med.su.oz.au (8.6.8.1/8.6.4) id OAA07263 Thu, 23 Feb 1995 14:11:04 +1100 From: Jeremy R Greenwood Message-Id: <199502230311.OAA07263@blackburn.med.su.oz.au> Subject: Summary: modelling protein under point mutation To: jabs@cis.biochemtech.uni-halle.de (Andreas Jabs) Date: Thu, 23 Feb 1995 14:11:03 +1100 (EST) Cc: chemistry@ccl.net In-Reply-To: <9502160954.AA10223@cis.biochemtech.uni-halle.de> from "Andreas Jabs" at Feb 16, 95 10:54:28 am X-Mailer: ELM [version 2.4 PL23] MIME-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7bit Content-Length: 12983 Thanks to all who responded to my request for information about protein structure determination under point mutation. There are some excellent suggestions. Jeremy Original request: ----------------------------------------------------------------------- Greetings to all, I have just been approached with a project concerning the modelling of the changes in structure and function of a protein under various point mutations. The X-ray crystal structure is known, as are all the different inherited single point mutations which lead to a particular pathology. Not being a protein modeller by trade, I'm asking for some preliminary qualitative advice: * Roughly how hard is it to model changes in structure or binding resulting from a single point mutation? (apparantly many such typical mutations are from charged to uncharged residues). Is it feasible to obtain meaningful results, given the state of the art? (obviously this will depend on the given system, but perhaps some out there have attempted this kind of problem previously.) * What kinds of tools are necessary or useful? (e.g. AMBER, MD, MC, simulated annealing, semi-empirical calculations on local regions with substrate binding, etc.) Which software packages are recommended (anything cheaper than Biosym?) and what level of hardware? * Any other advice for the neophyte protein modeller? Recommended texts? Summary to follow, as per usual. Naively, Jeremy ------------------------------------------------------------------------ >From bio320@cvx12.inet.dkfz-heidelberg.de Fri Feb 17 19:07:53 1995 I would recommend to use the comprehensive protein modelling software WHATIF, developed by Gert Vriend at EMBL Heidelberg. WHATIF was developed to answer such questions as "WHAT happens IF I do this or that mutation to my protein?". Although it is not very easy to use, compared to some glossy commercial software, it is extremely powerful, and cheap. Contact Gert at vriend@embl-heidelberg.de, if you are interested in this software. Good luck, - Friedrich - ------------------------------------------------------------------------------- Dr. Friedrich Rippmann work: c/o E.MERCK home: Pha Fo Chem, Drug Design Schroederstrasse 72 64271 Darmstadt 69120 Heidelberg +49-6221-413366 +49-6151-726290 Email: bio320@cvx12.inet.dkfz-heidelberg.de Fax ... 710757 -------------------------------------------------------------------------------- >From cox@CLASS.ORG Fri Feb 17 06:10:33 1995 Jeremy, Could you check out this reference and see if it is of any use to you? I'd be interested to know what you think. The authors have in fact offered to make available a program. P Koehl & M Delarue, "Polar and Nonpolar Atomic Environments in the Protein Core: Implications for Folding and Binding", PROTEINS: Structure, Function and Genetics 20:264-278 (1994). You should also hear from people working in site directed mutagensis, I understand they have other programs too. -- Harold Cox | cox@class.org | 510 231 1008 ---------------------------------------------------------------------- >From ross@cgl.ucsf.EDU Fri Feb 17 05:17:23 1995 In theory, you could do a perturbation of one residue to another; AMBER's free energy program does this. Since sampling is a big issue, there is a bit of art in doing this, so I'd advise reading papers on it.. no refs handy. the good news is that AMBER is pretty cheap, and the next release which is due 'any week' will have some graphics for setting up the molecule files. See http://www.amber.ucsf.edu Bill Ross ---------------------------------------------------------------------- >From polowin@hyper.hyper.com Fri Feb 17 03:57:22 1995 Hi, Jeremy. > * Roughly how hard is it to model changes in structure or binding > resulting from a single point mutation? (apparantly many such typical > mutations are from charged to uncharged residues). Is it feasible to > obtain meaningful results, given the state of the art? (obviously this > will depend on the given system, but perhaps some out there have > attempted this kind of problem previously.) Our HyperChem software trivially allows single-point mutations of proteins, and allows specific control over secondary-conformation details. The Sequence Editor module of the ChemPlus enhancements package is convenient for editing or generating proteins on a more abstract level, and then the resulting sequence can be returned to HyperChem. > * What kinds of tools are necessary or useful? (e.g. AMBER, MD, MC, > simulated annealing, semi-empirical calculations on local regions with > substrate binding, etc.) Which software packages are recommended > (anything cheaper than Biosym?) and what level of hardware? HyperChem will do all of the above except MC, with annealing being done via scripts or an external controller such as Visual Basic or Excel. The suggested retail price for HyperChem is US$1995 commercial/ $995 academic. Hardware requirements are a 386-or-better PC with math coprocessor, minimum 4MB RAM (it would be better to have considerably more RAM for macromolecule work), Windows 3.1, and the sorts of display, etc. that are standard with a system of that level. Regards, Joel ------------ Joel Polowin, Ph.D. Manager, Scientific Support Email to: polowin@hyper.com Hypercube Inc, 7-419 Phillip St, Waterloo, Ont, Canada N2L 3X2 (519)725-4040 Info requests to: info@hyper.com Support questions to: support@hyper.com Email group: Send "subscribe hyperchem" to hyperchem-request@hyper.com ----------------------------------------------------------------------- >From ryszard@msi.com Fri Feb 17 03:03:19 1995 Jeremy, You could try QUANTA/MODELER/CHARMm etc... try http://www.msi.com/ or hotline@msi.com to find out more. Sincerely, Ryszard Czerminski +------------------------------------------------------------------+ | Molecular Simulations Incorporated | phone : (617)229-8875 x 217 | | 16 New England Executive Park, | fax : (617)229-9899 | | Burlington, MA 01803-5297 | e-mail: ryszard@msi.com | +------------------------------------------------------------------+ ------------------------------------------------------------------------- >From harte@extreme.wf.bms.com Fri Feb 17 00:18:57 1995 Dear Jeremy, We have attempted modeling a mutant HIV-1 protease N88Q. This single mutation is known to prevent dimerization of the protease subunits. We were able to observe a destablization of the dimer interface by studying the MD trajectory for 100ps. We used WESDYN an MD package developed at Wesleyan University by S. Swaminathan. Our results were published in J. Am. Chem. Soc. (1993) 115, 1231-1234. Hope this helps. ------------------------------------------------------------------------------- .-----. / \-_-/ \ Bristol-Myers Squibb Pharmaceutical Research Institute /_-_\ /_-_\ ------------------------------------------------------ ----- ----- William E. Harte,Jr.,Ph.D. Internet Address: harte_w@bms.com \-_-/ \-_-/ Senior Research Investigator Telephone: 203-284-6913 \ /_-_\ / Computer Assisted Drug Discovery FAX: 203-284-7702 `-----' =============================================================================== >From KOEHLER@IRBM.IT Thu Feb 16 21:22:49 1995 Jeremy: One particularily interesting reference that relates to the problem of predicting changes in structure and binding properties of mutant proteins is by Wilson et al.[1] Using molecular mechanics with a solvent correction plus a protein side-chain rotamer library, these authors were able to design a mutant enzyme with altered substrate specificity and good selectivity. As Wilson et al. have done, you will probably need to consider alternative sied-chain conformations of the residue that has mutated as well as the immediately surounding residues. This is especially true of surface residues. For this purpose, the rotamer library of Dunbrack and Karplus is the most up-to-date.[2] This library along with a Fortran program for reading it are available directly from the author (dunbrack@cgl.ucsf.edu) or from anonymous ftp (babar.ucsf.edu). Finally, if you have access to Sybyl, I have written an SPL for assignment of sidechain conformation, given the coordinates of the backbone based on the Dunbrack and Karplus rotamer library. This is available via anonymous ftp (extreme.chem.rpi.edu), and the file is /pub/sybyl/spl/sarl.spl.Z. where SARL stands for Sidechain Assignment by Rotatmer Library. This script iteratively explores sidechain conformations taken from the rotamer library which minimize the number of bad contacts. The script also allows you to restrict the conformer search to a subset of residues. [1] Wilson, C.; Mace, J. E.; Agard, D. A. Computational method for the design of enzymes with altered substrate specificity. J. Mol. Biol. 1991, 220, 495-506. [2] Dunbrack, R. L., Jr.; Karplus, M. Backbone-dependent rotamer library for proteins. Application to side-chain prediction. J. Mol. Biol. 1993, 230, 543-574. I hope you find these references helpful. Ciao, Konrad ------------------------------------------------------------------ | Konrad Koehler | Computational Chemistry Group | | internet: koehler@irbm.it | Department of Medicinal Chemistry | | | IRBM | | telephone: +39-6-910-93606 | Via Pontina Km. 30,600 | | fax: +39-6-910-93225 | 00040 Pomezia (Roma) | | | Italy | ------------------------------------------------------------------ --------------------------------------------------------------------------- >From mmccar@postman.essex.ac.uk Thu Feb 16 20:56:59 1995 Hi Jeremy, You can mutate with AMBER during a MD simulation from one amino acid into another. I am doing such a mutation but with CHARMM but I'm not sure if you have this package. If this is what you looking for then I can mail you some references for AMBER or give you some advice about CHARMM. Mail me if I can help. regards Matthew McCarron e-mail: mmccar@essex.ac.uk ---------------------------------------------------------------------------- >From goulpj@postman.essex.ac.uk Thu Feb 16 20:09:42 1995 i am currently doing something similar to what you are suggesting and I find that Amber is quit capable of dealing with these mutations It is possible to change single residues in the link stage ie remove charge etc or even mutate the residue using WHATIF see Gert Vriend Heidleberg EMBL I do not have a full set of results yet but they look promising So in answer to your question Amber MD is quite sufficient Please mail me if you have any other ideas/questions goulpj@essex.ac.uk byee Paul >From byw@novo.dk Thu Feb 16 19:28:29 1995 ---------------------------------------------------------------------------- Received: from sentry.novo.dk (sentio.novo.dk [130.227.249.6]) From: byw@novo.dk (Robert Bywater) Message-Id: <9502160827.AA27194@ligand.novo.dk> To: jeremy@med.su.oz.au Status: OR Dear Jeremy You will find all the tools to do just what you want in the program package WHAT IF. This will enable you to do mutations, refinements of th e mutated protein(s) and a lot else besides. You will also need to do some MD, then you should get the program GROMOS. WHAT IF has an excellent interface to GROMOS. WHAT IF is available ( at close to zero cost ) from : Dr. Gert Vriend EMBL Heidelberg Germany email: Gert.Vriend@embl-heidelberg.de Very likely, you can get it by 'ftp' transfer, but he will arrange all that for you. WHAT IF is very easy to use, but it does take some practice, just like any program, in some ways more so, because of the ENORMOUS number of options. Oh, and you better make sure you have at least 1 Gb disk free for this program. I may be in OZ in August this year, and if so, could help you with a tutorial, as by now, I am one of the seasoned users. But maybe Gert wants to come to OZ. Anyway he will decide. Please tell hime I recommended WHAT IF to you. best regrds Robert Bywater ****************************** * * * Robert Bywater * * * * Biostructure Department * * NOVO NORDISK A/S * * * * email byw@novo.dk * * fax :: +45 4442 1400 * ****************************** ------------------------------------------------------------------------ From rosas@irisdav.chem.vt.edu Wed Feb 22 23:52:06 1995 Received: from irisdav.chem.vt.edu for rosas@irisdav.chem.vt.edu by www.ccl.net (8.6.9/930601.1506) id XAA25819; Wed, 22 Feb 1995 23:37:53 -0500 Received: by irisdav.chem.vt.edu (931110.SGI/931108.SGI.AUTO.ANONFTP) for chemistry@ccl.net id AA06231; Wed, 22 Feb 95 23:36:25 -0800 From: "Victor M. Rosas Garcia" Message-Id: <9502222336.ZM6229@irisdav.chem.vt.edu> Date: Wed, 22 Feb 1995 23:36:21 -0800 X-Mailer: Z-Mail (3.1.0 22feb94 MediaMail) To: chemistry@ccl.net Subject: CCL:COMPARING ISOMERS Content-Type: text/plain; charset=us-ascii Mime-Version: 1.0 Some people have mentioned algorithms for comparison of conformers and evidently the solution to this problem is far from simple. The best implementation I have seen to solve this problem is in the program GMMX, a global minimum search utility by Serena Software. As I understand it, the program calculates the RMS of the conformers by using identical numbering in the atoms of both conformers and, if necessary, checks for planes of symmetry and for the so-called numerical isomers. The idea is that making the atoms distinguishable by numbering them will introduce artificial conformers that differ only in the numbering but that are really "the same" conformer e.g. a product of a rotation or reflection or some other symmetry operation. Victor.