From lim@rani.chem.yale.edu Fri Mar 24 01:52:58 1995 Received: from rani.chem.yale.edu for lim@rani.chem.yale.edu by www.ccl.net (8.6.10/930601.1506) id BAA06937; Fri, 24 Mar 1995 01:51:50 -0500 Received: by rani.chem.yale.edu; Fri, 24 Mar 95 01:51:50 -0500 From: Dongchul Lim Message-Id: <9503240651.AA16610@rani.chem.yale.edu> Subject: Constrained Optimization Methods To: chemistry@ccl.net (Computational Chemistry) Date: Fri, 24 Mar 95 1:51:50 EST In-Reply-To: <9503232048.AA07252@andromeda>; from "Eric Martin" at Mar 23, 95 12:48 pm X-Mailer: ELM [version 2.3 PL11] There has been some discussion on the subject of 'optimization with constraints' in this mailing list. A while ago, I happened to be interested in "constrained optimization without derivatives". Although this is about non-gradient optimization methods, it is possible to use derivatives as well in most methods. The following summary is what I collected from the usenet and private communications. I hope this information will be helpful. Dongchul Lim, Department of Chemistry, Yale Univ. < Summary of Constrained Optimization without Derivatives > _________________________________________________________________________ From mcintosh@bellcore.com Fri Mar 10 08:20:02 1995 Try David Gay's dmnfb code from netlib. _________________________________________________________________________ From be478@freenet.carleton.ca Mon Mar 13 09:10:36 1995 The following newly published book is for your possible interest. Title : "A NUMERICAL LIBRARY IN C FOR SCIENTISTS AND ENGINEERS" (ISBN 0-8493-7376-X), 1995 Publisher : CRC Press, Inc. 2000 Corporate Blvd., N.W. Boca Raton, FL 33431 USA telephone: (407)-994-0555 This book contains an extensive coverage of computer programs in numerical computing, with several hundred procedures including areas in Linear Algebra Ordinary and Partial Differential Equations (stiff and non-stiff systems) Optimization Parameter Estimation Special Functions in mathematical physics. A diskette is included with all the source code. _________________________________________________________________________ From kassarji@stripe.Colorado.EDU Fri Mar 10 16:27:59 1995 I refer you to Fletcher's book, _Practical Methods of Constrained Optimization_ (or something like that). For simple bounds, the algorithms will probably be BFGS with Active Set (to convert the inequality constraints into equality constraints when the inequality constraint is violated) and Lagrange multipliers to handle the resulting equality constraints (or some other method for linear constraints). _________________________________________________________________________ From jpc@a.cs.okstate.edu Fri Mar 10 16:03:48 1995 You inquired about direct search methods for minimizing a function subject to constraints. I have FORTRAN software available via anonymous ftp: see files readme.opt, marq.f, stepit.f, and simplex.f in directory /pub/jpc at a.cs.okstate.edu . MARQ is for nonlinear (or linear) least squares problems only. STEPIT and SIMPLEX are direct search minimizers. All allow the use of XMIN(J) and XMAX(J) limits on the parameters X(J). STEPIT and SIMPLEX are interchangeable; MARQ is nearly so. This software is robust, portable, and supported (by me). It has been used at many sites for over twenty years. It can be used and distributed freely. If you have any further questions, send e-mail. Good luck. John Chandler _________________________________________________________________________ From borchers@prism.nmt.edu Fri Mar 10 13:28:17 1995 If the objective function is smooth, then you should consider an implementation of a quasi-newton method such as BFGS, using finite difference approximations. If the objective function is not smooth, then you should look at methods for "nonsmooth optimization". You should probably take a look at "Optimization Software Guide" by More and Wright. It has listing of dozens of optimization packages for different types of problems. _________________________________________________________________________ From obal@pmrl-gw.ece.arizona.edu Fri Mar 10 11:23:27 1995 Check out netlib by ftp to netlib.att.com, directory netlib. There is a lot of numerical code there. Specifically, if you like C, in netlib/c/brent.shar.Z and serv.shar.Z there are routines that will do what you ask. (I think most of the code in netlib is FORTRAN; you may prefer that anyway.) _________________________________________________________________________ From: John D'Errico I know this is not the best solution possible (so please cool the flames) but a trick that has worked for me when I was looking to constrain a variable in an optimization without resorting to a constrained code is to introduce a transformation of variables. If you want a variable x to be constrained to the interval [a,b], simply substitute x = a + (b-a)*(sin(z)+1)/2 When the optimizer returns z, run it through the transformation to determine x. If all you want is to introduce a lower bound, this can be accomplished by x = a + z^2 (Do not try to use an absolute value function as it will introduce a singularity at z=0. This will confuse gradient based methods to no end.) This allows you to use an unconstrained code on the variable z. Again, I admit this method has its flaws, but it does work in a pinch. You have to accept that there are suddenly many local optima, though all of the ones so introduced will be equivalent. You may also end up introducing significant extra curvature into what was once a well behaved function. Finally, if you are using this trick on a nonlinear least squares problem, then estimates of confidence regions for the variables will no longer be correct. _________________________________________________________________________ From mjohnson@netcom19.netcom.com John D'Errico suggests using penalty functions as a quick-and-dirty (but extremely useful) way of getting an unconstrained optimization software package to do bounds-constrained problems. He gives examples of continuous penalty functions. I'll point out that if you use an optimization algorithm such as NelderMead Simplex or HookeJeeves (which doesn't require the objective function to be differentiable), then you can use DIScontinuous penalty functions and/or barrier functions. These have the advantage of not introducing any false minima inside the constraint boundaries, because they only modify the objective function beyond the boundaries. A simple example: find the minimum of y= tan(log(x) - 3x) * cos(1/x^2) subject to the constraints x>=4.0 and x<10.0 Discontinuous penalty function approach: let f(x) = tan(log(x) - 3x) * cos(1/x^2) if(x < 4.0) then return( f(4.0) * 10.0 * (1.0 + (4.0-x)^2) ) ; if(x >= 10.0) then return( f(10.0) * 10.0 * (1.0 + (x-10.0)^2) ) ; return( f(x) ); _________________________________________________________________________ From JeanLuc.Verschelde@rug.ac.be Fri Mar 24 03:23:01 1995 Received: from mserv.rug.ac.be for JeanLuc.Verschelde@rug.ac.be by www.ccl.net (8.6.10/930601.1506) id DAA07712; Fri, 24 Mar 1995 03:20:52 -0500 Received: from allserv.rug.ac.be by mserv.rug.ac.be with SMTP id AA26914 (5.67b/IDA-1.5 for ); Fri, 24 Mar 1995 09:19:51 +0100 Received: by allserv.rug.ac.be (5.x/SMI-SVR4) id AA26880; Fri, 24 Mar 1995 09:20:53 +0100 Date: Fri, 24 Mar 1995 09:20:53 +0100 (MET) From: Jean-Luc Verschelde To: OHIO SUPER Subject: Summary:Minimization algorithm Message-Id: Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII From rs0thp@rohmhaas.comFri Mar 24 09:13:04 1995 Date: Thu, 2 Mar 1995 08:44:06 -0500 (EST) From: "Dr. Tom Pierce" To: Jean-Luc Verschelde Cc: chemistry@ccl.net Subject: CCL:simplex Previously, Jean-Luc Verschelde wrote: > Where can I find minimization algorithms? > The simplex procedure would be nice. I find excellent numerical software at: http://www.netlib.org and http://gams.nist.gov The GAMS "Guide to Available Mathematical Software" can be accessed by telnetting to gams.nist.gov and following the instructions. -- Sincerely, Thomas Pierce - THPierce@RohmHaas.Com - Computational Chemist "These opinions are those of the writer and not the Rohm and Haas Company." -------This is added Automatically by the Software-------- -- Original Sender Envelope Address: rs0thp@rohmhaas.com -- Original Sender From: Address: rs0thp@rohmhaas.com 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 From CHERM@frcpn11.in2p3.frFri Mar 24 09:13:34 1995 Date: Fri, 03 Mar 95 17:02:06 MET From: Henry Chermette To: Jean-Luc Verschelde Subject: Re: CCL:simplex you may find materials, including soft. in "numerical recipes" by Press, Flannery, Teukolsky and Vetterling Cambridge University Press, 1st ed. 1986, 2nd 1990 ? you may find robust minimization algorithms, including simplex (Minuit) in the CERNlib, distributed (no charges) by CERN in Geneva. Henry Chermette Institut de Physique Nucleaire de Lyon 43 bd du 11 novembre 1918 F-69622 VILLEURBANNE Cedex Tel (33) 72 44 84 27 Fax (33) 72 44 80 04 e-mail CHERM@FRCPN11.in2p3.fr From JeanLuc.Verschelde@rug.ac.be Fri Mar 24 03:23:04 1995 Received: from mserv.rug.ac.be for JeanLuc.Verschelde@rug.ac.be by www.ccl.net (8.6.10/930601.1506) id DAA07705; Fri, 24 Mar 1995 03:19:48 -0500 Received: from allserv.rug.ac.be by mserv.rug.ac.be with SMTP id AA26898 (5.67b/IDA-1.5 for ); Fri, 24 Mar 1995 09:18:23 +0100 Received: by allserv.rug.ac.be (5.x/SMI-SVR4) id AA26862; Fri, 24 Mar 1995 09:19:25 +0100 Date: Fri, 24 Mar 1995 09:19:24 +0100 (MET) From: Jean-Luc Verschelde To: OHIO SUPER Subject: Summary:Monte-Carlo Message-Id: Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII From arne@hodgkin.mbi.ucla.eduFri Mar 24 09:07:52 1995 Date: Sat, 25 Feb 95 14:45:58 -0800 From: "Arne Eofsson (arne@uclaue.mbi.ucal.edu)" To: Jean-Luc Verschelde Subject: Re: CCL:Monte carlo The latest advances are a set of Genetic Algorithms see dandekar & Argos, Legrand & Merz, Bowie & Eisenber & S. Sun (all have a set of papers lately) for simplified models see work by Dill and by Shahknowitz for lattice models see work by Skolnick for my latest paper (submitted to Proteins (with a lot of references)) see http://www.mbi-doe.ucla.edu/arne/grail.ps good luck arne From KOEHLER@IRBM.ITFri Mar 24 09:08:04 1995 Date: Sun, 26 Feb 1995 14:44:26 +0100 (WET) From: "Konrad, IRBM Chemistry, +39-6-91093606" To: Jeanluc.Verschelde@rug.ac.be Cc: KOEHLER@IRBM.IT Subject: RE: CCL:Monte carlo references Jean-Luc: The following reference would seem relevant to faster/smarter sampling of protein conformational space: Guarnieri, F.; Still, W. C. A rapidly convergent simulation method: mixed Monte Carlo/stochastic dynamics. J. Comput. Chem. 1994, 15, 1302-1309. For recent refs on low resolution (lattice protein model) sampling of conformational states: Sali, A.; Shakhnovich, E.; Karplus, M. How does a protein fold? Nature 1994, 369, 248-251. Sali, A.; Shakhnovich, E.; Karplus, M. Kinetics of protein folding. A lattice model study of the requirements for folding to the native state. J. Mol. Biol. 1994, 235, 1614-1636. 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 bhardy@convex.ox.ac.ukFri Mar 24 09:08:20 1995 Date: Mon, 27 Feb 1995 08:59:47 +0100 From: Barry Hardy To: JeanLuc.Verschelde@rug.ac.be Subject: Re: CCL:Monte carlo Jean-Luc, I have a couple of recent papers on efficient Monter Carlo sampling which you may find interesting. Try: 1) http://alcyone.pcl.ox.ac.uk/people/barry_eccc_final/paper_text.html 2) B.J. Hardy and R.W. Pastor, J. Comp. Chem., 15, 208 (1994) (This paper also references papers on several other MC methods). Drop me an email if you want to discuss any of this. All the best, Barry Barry J. Hardy An Oxford_Attraction: http://alcyone.pcl.ox.ac.uk/people/barry.html From maxv@iserver.pdl.comFri Mar 24 09:08:45 1995 Date: Mon, 27 Feb 95 09:31:00 -0800 From: Max Vasquez To: Jeanluc.Verschelde@rug.ac.be Subject: Monte Carlo of peptides (proteins) I have recently written a review of energy calculations on peptides and proteins (Chemical Reviews 94, 2183 [1994]) that includes sections on simulated annealing, Monte Carlo-Minimization, and other stochastic methods. I'd be happy to send you a reprint if you are interested. Some of the most intriguing methods belong to the class of "multicanonical" algorithms (and the equivalent "entropy-sampling" procedures). These have been used to treat full-atom models of small peptides (Hansmann & Okamoto J. Comp. Chem. 14, 1333 [1993]) as well as lattice models of proteins (Hao & Scheraga J. Phys. Chem. 98, 4940 [1994]). The conventional "wisdom" has been that MC is not competetive with MD for larger polypeptides and proteins (Northrup & McCammon Biopolymers 19, 1001 [1980]); some new methods may be starting to change this perception, particularly Bouzida, Kumar & Swendsen Physical Review A 45, 8894 [1992] as well as work by Bouzida et al in Protein Science 3, 911 [1994]. One should also distinguish between MC methods used for conformational search and methods used to generate ensemble averages distributed according to a Boltzmann distribution at a given temperature. Many MC methods in the literature of peptides and protein are not "theoretically guaranteed" to preserve proper sampling, although they may still be excellent "search tools." This issue is discussed a bit in the review mentioned above, as well as in Vasquez et al. J. Phys. Chem. 98, 9380 [1994] and in Gibrat et al Immunomethods 1, 107 [1992]. The first paper deals with small *isolated* peptides while the second deals with loops of peptide *segments* that are part of a full protein. Hope this helps; best wishes, Max ************************************************ Max Vasquez, PhD Protein Design Labs, Inc. 2375 Garcia Ave. Mountain View, CA 94043 (415) 903-3744 (415) 903-3730 (FAX) Internet: maxv@pdl.com ************************************************* From mrigank@imtech.ernet.inFri Mar 24 09:09:45 1995 Date: Fri, 3 Mar 95 11:36:26 +0530 From: mrigank@imtech.ernet.in To: JeanLuc.Verschelde@rug.ac.be Subject: RE: CCL:Monte carlo ==>Hi all, ==> ==> I want to use advanced Monte Carlo to explore protein spaces. ==> Can someone give me references of the newest methods to ==> sample more efficiently or smarter. ==> ==> Thanks, ==> ==> Jean-Luc ==> I guess BOSS from W.L. Jorgensen lab will solve your problem. he can be reached at Dept. of chemistry, Yale university New Haven, Connecticut 06511 USA email: bill@doctor.chem.yale.edu If you get anything 'smarter' pls. let me know as well. Mrigank ---- /Mrigank \/ Phone +91 172 690557 \ \Institute of Microbial Technology /\ Email: mrigank@imtech.ernet.in / /Sector 39A, \/ FAX: +91 172 690585 \ \Chandigarh 160 014 India. /\ / \//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\// -- When I feed the poor, they call me saint. When I ask why the poors do not have food, they call me communist - Archbishop Camaran From praa2@cluster1.urz.uni-halle.de Fri Mar 24 03:53:00 1995 Received: from mlucom.urz.uni-halle.de for praa2@cluster1.urz.uni-halle.de by www.ccl.net (8.6.10/930601.1506) id DAA07811; Fri, 24 Mar 1995 03:45:07 -0500 From: Received: from cluster1.urz.Uni-Halle.DE by mlucom.urz.uni-halle.de with SMTP (1.36.108.7/15.6) id AA18023; Fri, 24 Mar 1995 09:43:36 +0100 Posted-Date: Fri, 24 Mar 1995 09:45:18 +0100 (MEZ) Received-Date: Fri, 24 Mar 1995 09:43:36 +0100 Received: by cluster1.urz.uni-halle.de (AIX 3.2/UCB 5.64/4.03) id AA19977; Fri, 24 Mar 1995 09:45:19 +0100 Message-Id: <9503240845.AA19977@cluster1.urz.uni-halle.de> Subject: gaussian lobe code available To: chemistry@ccl.net Date: Fri, 24 Mar 1995 09:45:18 +0100 (MEZ) X-Mailer: ELM [version 2.4 PL22] Content-Type: text Content-Length: 224 Dear Netters, I am looking for a free of charge available code for doing calculations within the gaussian lobe (as proposed by frost) framework. Any hints or pointers are highly appriciated. Many thankx in advance Susi From dqugss8@PS.uib.es Fri Mar 24 08:08:03 1995 Received: from relay.rediris.es for dqugss8@PS.uib.es by www.ccl.net (8.6.10/930601.1506) id IAA09171; Fri, 24 Mar 1995 08:02:36 -0500 Received: from rediris.es by relay.rediris.es (PMDF V4.2-14 #4193) id <01HOILGFIJKW8WZ14U@relay.rediris.es>; Fri, 24 Mar 1995 13:45:24 GMT+1 X400-Received: by mta iris-dcp in /PRMD=iris/ADMD=mensatex/C=es/; Relayed; Fri, 24 Mar 1995 13:43:51 UTC+0100 X400-Received: by /PRMD=iris/ADMD=mensatex/C=es/; Relayed; Fri, 24 Mar 1995 13:42:45 UTC+0200 Date: Fri, 24 Mar 1995 13:42:45 UTC+0200 From: GUILLEM SUŅER Subject: DEC Xmol package To: CHEMISTRY@ccl.net Message-id: <573*/S=dqugss8/OU=PS/O=uib/PRMD=iris/ADMD=mensatex/C=es/@MHS> Content-identifier: 573 Content-transfer-encoding: 7BIT X400-Content-type: P2-1984 (2) X400-MTS-identifier: [/PRMD=iris/ADMD=mensatex/C=es/;950324134245] X400-Originator: dqugss8@PS.uib.es X400-Recipients: CHEMISTRY@ccl.net Dear Netters, I would like to know if there is the Xmol software package for DEC alpha platforms, and if this program is suitable via anon. ftp. Thanks in advance for any help ---------------------------------------------------------------------------- Dr Guillermo A. Suner. E-mail: dqugss8@ps.uib.es Tel: + 34 71 173498 UNIVERSITAT DE LES ILLES BALEARS Fax: + 34 71 173426 Departament de Quimica WWW URL: http://www.uib.es/depart/ Ctra. Valldemossa, Km 7.5 dqu/dquo/suner.html E-07071-Palma de Mallorca Baleares ''' SPAIN (0 0) ----- *Beyond the FAR SIDE of Chemistry* +---OOo--(_)--oOO---+ From WSMITH@msnet.mathstat.uoguelph.ca Fri Mar 24 08:23:03 1995 Received: from ccshst06.cs.uoguelph.ca for WSMITH@msnet.mathstat.uoguelph.ca by www.ccl.net (8.6.10/930601.1506) id IAA09310; Fri, 24 Mar 1995 08:19:27 -0500 From: Received: from msnet.nw.uoguelph.ca (msnet.mathstat.uoguelph.ca) by ccshst06.cs.uoguelph.ca with SMTP (1.37.109.14/16.2) id AA009131245; Fri, 24 Mar 1995 08:20:45 -0500 Received: from MSNET/MAILQ by msnet.nw.uoguelph.ca (Mercury 1.11); Fri, 24 Mar 95 8:19:25 GMT-5 Received: from MAILQ by MSNET (Mercury 1.11); Fri, 24 Mar 95 8:19:17 GMT-5 Organization: Dept. of Math & Stats. To: chemistry@ccl.net Date: Fri, 24 Mar 1995 08:19:11 EDT Subject: Re: CCL:Re: CCL:optimization with constraints X-Pmrqc: 1 Priority: normal X-Mailer: Pegasus Mail v3.1 (R1a) Message-Id: <18A52BF2A0A@msnet.nw.uoguelph.ca> Hello, Eric Martin wrote: > >My understanding is that fitting a transformed function might not only >affect the efficiency, it can also affect the answer. The least >squares best fit of the transformed problem will have different >parameter values (even after the reverse transorm) than the best fit of >the untransformed (albeit constrained) problem, since the sum of >squared residuals of a different function is being minimized. This can >sometimes be rectified by applying weighted least squares. See: >"When, Why and How to Use Weighted Least Squares", Robert de Levie, J. >Chem. Edu., 63, (1986) p. 10. This is a very good point, but it refers to a transformed _model_, not to constraints on the model itself (the latter being a purely computational issue). A classic example is y = A \exp (b*x) (1) with additive error. In the old days (before computers), this would be changed to \log (y) = A' + bx (2) which is now a linear model (in terms of the parameters A and b). One can now use "good old linear regression" to solve this problem. However, as Eric correctly points out, this is only (statistically) correct if the error is _additive_ in Eqn. (2). Of course, if the error was additive in (1), this surely will not be the case in (2). The parameter values resulting from the 2 fits will indeed be different. One can (partially) compensate for the transformation by _weighting_ the residuals in fitting Eqn (2). In general, the weights for a transformation f(y) are given by w_i = \frac{1}{f'(y_{i}}^2} which in the case of (2) becomes w_i = \frac{1}{y_{i}^2} (Of course, the above comments also assume normally distributed errors with equal variances, etc.) I never cease to be amazed by the fact that regression (and parameter estimation) is taught so poorly in universities - it's as if computers had never been invented! There's a _huge_ emphasis on linear models and on normally distributed errors, and neglect of many important topics (errors in the independent variables, nonlinear models, non-normal error distributions, .... ) Maybe it's related to the fact that beginning stats courses (where regression is first taught) are oriented towards the social sciences - where there is no such thing as a "fundamental law" and one might as well use a linear model. Some years ago, I wrote a report discussing the above and other problems related to nonlinear parameter estimation. If anyone would like a copy, please send me an E-Mail request. Best Regards, W. R. Smith Professor Dept. of Mathematics and Statistics and School of Engineering University of Guelph FAX: 519-837-0221 Guelph, Ontario Tel: 519-824-4120, ext. 3038 CANADA N1G 2W1 From chuang@iris.bc.ntu.edu.tw Fri Mar 24 09:23:04 1995 Received: from iris.bc.ntu.edu.tw for chuang@iris.bc.ntu.edu.tw by www.ccl.net (8.6.10/930601.1506) id JAA09973; Fri, 24 Mar 1995 09:14:06 -0500 From: Received: by iris.bc.ntu.edu.tw (920330.SGI/920502.SGI) for chemistry@ccl.net id AA17530; Fri, 24 Mar 95 22:16:05 -0800 Date: Fri, 24 Mar 95 22:16:05 -0800 Message-Id: <9503250616.AA17530@iris.bc.ntu.edu.tw> To: xplor-l@msi.com Subject: Any experience about DNA dg-sa for structural deter. by XPLOR Cc: molmodel@net.bio.net, chemistry@ccl.net, str-nmr@net.bio.net, quanta-l@msi.com Dear Netters: I am doing a computer modelling work to determine a DNA structure by dg-sa protocol using XPLOR package. Does any people has the experience on this ? My trouble is in the dg_sub_embed step. Could you share your *.inp files with me, or give me some suggestions how to choose the subset atoms in DNA case? Any suggestion will be great appriciated. Thanks all. ccchuang ============================================================ Chyh-Chong Chuang Institude of Biological Chemistry, Academia Sinica,Taipei, Taiwan ------------------------------------------------------------ P.O. BOX 23-106, Phone: (02) 362-0261 ext 2021 Taipei, Taiwan, Fax: (02) 363-5038 R.O.C. E-Mail: chuang@bc.ntu.edu.tw ============================================================ From JeanLuc.Verschelde@rug.ac.be Fri Mar 24 03:19:56 1995 Received: from mserv.rug.ac.be for JeanLuc.Verschelde@rug.ac.be by www.ccl.net (8.6.10/930601.1506) id DAA07705; Fri, 24 Mar 1995 03:19:48 -0500 Received: from allserv.rug.ac.be by mserv.rug.ac.be with SMTP id AA26898 (5.67b/IDA-1.5 for ); Fri, 24 Mar 1995 09:18:23 +0100 Received: by allserv.rug.ac.be (5.x/SMI-SVR4) id AA26862; Fri, 24 Mar 1995 09:19:25 +0100 Date: Fri, 24 Mar 1995 09:19:24 +0100 (MET) From: Jean-Luc Verschelde To: OHIO SUPER Subject: Summary:Monte-Carlo Message-Id: Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII >From arne@hodgkin.mbi.ucla.eduFri Mar 24 09:07:52 1995 Date: Sat, 25 Feb 95 14:45:58 -0800 From: "Arne Eofsson (arne@uclaue.mbi.ucal.edu)" Subject: Re: CCL:Monte carlo The latest advances are a set of Genetic Algorithms see dandekar & Argos, Legrand & Merz, Bowie & Eisenber & S. Sun (all have a set of papers lately) for simplified models see work by Dill and by Shahknowitz for lattice models see work by Skolnick for my latest paper (submitted to Proteins (with a lot of references)) see http://www.mbi-doe.ucla.edu/arne/grail.ps good luck arne >From KOEHLER@IRBM.ITFri Mar 24 09:08:04 1995 Date: Sun, 26 Feb 1995 14:44:26 +0100 (WET) From: "Konrad, IRBM Chemistry, +39-6-91093606" Subject: RE: CCL:Monte carlo references Jean-Luc: The following reference would seem relevant to faster/smarter sampling of protein conformational space: Guarnieri, F.; Still, W. C. A rapidly convergent simulation method: mixed Monte Carlo/stochastic dynamics. J. Comput. Chem. 1994, 15, 1302-1309. For recent refs on low resolution (lattice protein model) sampling of conformational states: Sali, A.; Shakhnovich, E.; Karplus, M. How does a protein fold? Nature 1994, 369, 248-251. Sali, A.; Shakhnovich, E.; Karplus, M. Kinetics of protein folding. A lattice model study of the requirements for folding to the native state. J. Mol. Biol. 1994, 235, 1614-1636. 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 bhardy@convex.ox.ac.ukFri Mar 24 09:08:20 1995 Date: Mon, 27 Feb 1995 08:59:47 +0100 From: Barry Hardy Subject: Re: CCL:Monte carlo Jean-Luc, I have a couple of recent papers on efficient Monter Carlo sampling which you may find interesting. Try: 1) http://alcyone.pcl.ox.ac.uk/people/barry_eccc_final/paper_text.html 2) B.J. Hardy and R.W. Pastor, J. Comp. Chem., 15, 208 (1994) (This paper also references papers on several other MC methods). Drop me an email if you want to discuss any of this. All the best, Barry Barry J. Hardy An Oxford_Attraction: http://alcyone.pcl.ox.ac.uk/people/barry.html >From maxv@iserver.pdl.comFri Mar 24 09:08:45 1995 Date: Mon, 27 Feb 95 09:31:00 -0800 From: Max Vasquez To: Jeanluc.Verschelde@rug.ac.be Subject: Monte Carlo of peptides (proteins) I have recently written a review of energy calculations on peptides and proteins (Chemical Reviews 94, 2183 [1994]) that includes sections on simulated annealing, Monte Carlo-Minimization, and other stochastic methods. I'd be happy to send you a reprint if you are interested. Some of the most intriguing methods belong to the class of "multicanonical" algorithms (and the equivalent "entropy-sampling" procedures). These have been used to treat full-atom models of small peptides (Hansmann & Okamoto J. Comp. Chem. 14, 1333 [1993]) as well as lattice models of proteins (Hao & Scheraga J. Phys. Chem. 98, 4940 [1994]). The conventional "wisdom" has been that MC is not competetive with MD for larger polypeptides and proteins (Northrup & McCammon Biopolymers 19, 1001 [1980]); some new methods may be starting to change this perception, particularly Bouzida, Kumar & Swendsen Physical Review A 45, 8894 [1992] as well as work by Bouzida et al in Protein Science 3, 911 [1994]. One should also distinguish between MC methods used for conformational search and methods used to generate ensemble averages distributed according to a Boltzmann distribution at a given temperature. Many MC methods in the literature of peptides and protein are not "theoretically guaranteed" to preserve proper sampling, although they may still be excellent "search tools." This issue is discussed a bit in the review mentioned above, as well as in Vasquez et al. J. Phys. Chem. 98, 9380 [1994] and in Gibrat et al Immunomethods 1, 107 [1992]. The first paper deals with small *isolated* peptides while the second deals with loops of peptide *segments* that are part of a full protein. Hope this helps; best wishes, Max ************************************************ Max Vasquez, PhD Protein Design Labs, Inc. 2375 Garcia Ave. Mountain View, CA 94043 (415) 903-3744 (415) 903-3730 (FAX) Internet: maxv@pdl.com ************************************************* >From mrigank@imtech.ernet.inFri Mar 24 09:09:45 1995 Date: Fri, 3 Mar 95 11:36:26 +0530 From: mrigank@imtech.ernet.in To: JeanLuc.Verschelde@rug.ac.be Subject: RE: CCL:Monte carlo ==>Hi all, ==> ==> I want to use advanced Monte Carlo to explore protein spaces. ==> Can someone give me references of the newest methods to ==> sample more efficiently or smarter. ==> ==> Thanks, ==> ==> Jean-Luc ==> I guess BOSS from W.L. Jorgensen lab will solve your problem. he can be reached at Dept. of chemistry, Yale university New Haven, Connecticut 06511 USA email: bill@doctor.chem.yale.edu If you get anything 'smarter' pls. let me know as well. Mrigank ---- /Mrigank \/ Phone +91 172 690557 \ \Institute of Microbial Technology /\ Email: mrigank@imtech.ernet.in / /Sector 39A, \/ FAX: +91 172 690585 \ \Chandigarh 160 014 India. /\ / \//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\//\// -- When I feed the poor, they call me saint. When I ask why the poors do not have food, they call me communist - Archbishop Camaran From JeanLuc.Verschelde@rug.ac.be Fri Mar 24 03:20:57 1995 Received: from mserv.rug.ac.be for JeanLuc.Verschelde@rug.ac.be by www.ccl.net (8.6.10/930601.1506) id DAA07712; Fri, 24 Mar 1995 03:20:52 -0500 Received: from allserv.rug.ac.be by mserv.rug.ac.be with SMTP id AA26914 (5.67b/IDA-1.5 for ); Fri, 24 Mar 1995 09:19:51 +0100 Received: by allserv.rug.ac.be (5.x/SMI-SVR4) id AA26880; Fri, 24 Mar 1995 09:20:53 +0100 Date: Fri, 24 Mar 1995 09:20:53 +0100 (MET) From: Jean-Luc Verschelde To: OHIO SUPER Subject: Summary:Minimization algorithm Message-Id: Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII >From rs0thp@rohmhaas.comFri Mar 24 09:13:04 1995 Date: Thu, 2 Mar 1995 08:44:06 -0500 (EST) From: "Dr. Tom Pierce" Subject: CCL:simplex Previously, Jean-Luc Verschelde wrote: > Where can I find minimization algorithms? > The simplex procedure would be nice. I find excellent numerical software at: http://www.netlib.org and http://gams.nist.gov The GAMS "Guide to Available Mathematical Software" can be accessed by telnetting to gams.nist.gov and following the instructions. -- Sincerely, Thomas Pierce - THPierce@RohmHaas.Com - Computational Chemist "These opinions are those of the writer and not the Rohm and Haas Company." >From CHERM@frcpn11.in2p3.frFri Mar 24 09:13:34 1995 Date: Fri, 03 Mar 95 17:02:06 MET From: Henry Chermette Subject: Re: CCL:simplex you may find materials, including soft. in "numerical recipes" by Press, Flannery, Teukolsky and Vetterling Cambridge University Press, 1st ed. 1986, 2nd 1990 ? you may find robust minimization algorithms, including simplex (Minuit) in the CERNlib, distributed (no charges) by CERN in Geneva. Henry Chermette Institut de Physique Nucleaire de Lyon 43 bd du 11 novembre 1918 F-69622 VILLEURBANNE Cedex Tel (33) 72 44 84 27 Fax (33) 72 44 80 04 e-mail CHERM@FRCPN11.in2p3.fr From aentrena@ugr.es Fri Mar 24 11:08:06 1995 Received: from ocelote.cica.es for aentrena@ugr.es by www.ccl.net (8.6.10/930601.1506) id LAA12219; Fri, 24 Mar 1995 11:00:52 -0500 Received: (from ean@localhost) by ocelote.cica.es (8.6.9/8.6.9) id QAA11125 for chemistry@ccl.net; Fri, 24 Mar 1995 16:52:21 +0100 X400-Received: by mta rica in /PRMD=/ADMD=/C=/; Relayed; Fri, 24 Mar 1995 16:29:35 UTC+0100 X400-Received: by /PRMD=iris/ADMD=mensatex/C=es/; Relayed; Fri, 24 Mar 1995 16:29:35 UTC+0100 X400-Received: by /PRMD=es/ADMD=/C=/; Relayed; Fri, 24 Mar 1995 16:30:12 UTC+0200 Date: Fri, 24 Mar 1995 16:30:12 UTC+0200 X400-Originator: aentrena@ugr.es X400-Recipients: non-disclosure:; X400-Content-Type: P2-1984 (2) X400-MTS-Identifier: [/PRMD=es/ADMD=/C=/;950324163012] Content-Identifier: <9412211320.AA14815@cemes.cemes.fr> Conversion: Prohibited From: bonvoisi@cemes.cemes.fr Sender: Computational Chemistry List To: chemistry@ccl.net Cc: bonvoisi@cemes.cict.fr Message-ID: <9412211320.AA14815@cemes.cemes.fr> Subject: CCL:Molecular Orbital MIME-Version: 1.0 (Generated by Ean X.400 to MIME gateway) >Errors-to: ccl@ccl.net >X-Envelope-to: AENTRENA@ugr.es, jaouad@ugr.es >X-Mailer: ELM [version 2.3 PL11] >Precedence: bulk Dear Netters, Recently I asked for programs able to draw or view Molecular Orbital issued from MOPAC type calculations. I got several answers and thanks for that. I wanted free and ftp'able programs. Among them, there were : PSI88, MOLDEN, MOPLOT2, SciAn, EDMOL. For my purpose, the best I try so far was PSI88 although there is some problem: - It works fine for small molecules ie with atoms numbers in the order of 10-20, but it did not seem to work with bigger molecules ie 40-50 atoms. Does somebody know why ? - Is there any mailing-list associated with this program ? I am trying to test the other cited-above program to see if they do better. Greetings. Bye. -- +----------------------------------------------------------------+ | Jacques BONVOISIN | | CNRS/CEMES-LOE Tel : +33 62 25 78 52 | | 29 , rue Jeanne Marvig Fax : +33 62 25 79 99 | | F-31055 Toulouse Cedex Email: bonvoisi@cemes.fr | +----------------------------------------------------------------+ -------This is added Automatically by the Software-------- -- Original Sender Envelope Address: bonvoisi@cemes.cemes.fr -- Original Sender From: Address: bonvoisi@cemes.cemes.fr 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 From steve@carbo.chem.binghamton.edu Fri Mar 24 11:15:36 1995 Received: from carbo.chem.binghamton.edu for steve@carbo.chem.binghamton.edu by www.ccl.net (8.6.10/930601.1506) id KAA12163; Fri, 24 Mar 1995 10:59:11 -0500 Received: by carbo.chem.binghamton.edu (931110.SGI/931108.SGI.ANONFTP) for chemistry@ccl.net id AA03097; Fri, 24 Mar 95 10:44:45 -0500 Date: Fri, 24 Mar 1995 10:39:34 -0500 (EST) From: Steven Schafer Subject: Re: Drug Design To: chemistry@ccl.net Message-Id: Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII I posted a week or so ago that I would send the summary of responses to anyone who wanted it insteasd of posting it to the net. Well, I intended to save bandwidth but have recieved over 500 requests. I have sent out a few of the summaries but I can not do 500. My appologies to anyone who I have not gotten it to and to those who may be ticked that I am going to now post it here. Anyways here it is: ============================================================================ A book chapter entitled "Successes of Computer-Assisted Molecular DEsign" by Don Boyd, previously of Eli Lilly and Co. is chapter 10 in Reviews of Computational Chemistry, Volume 1, pp355, 1990. It lists several drugs etc. that have been designed with the aid of computational methods. ============================================================================= From the archives, By the way, the first success in comp.-aided molecular modeling in Japan might be ACE inhibitor from Takeda. They developed CV-3317(?), that is in market now, and they analized usign extended huckle. And they found 7-membered ring is very much stable and suitable conformer. Then they developed 7-membered ring derivatives. Among them, CV-597X(?) was chosen. After that I do not know. Please ask Dr.Kamiya(Takeda). And Sankyo researchers developed gastrin antagonist using gastrin as a template about 10 years ago. I do not well about this. I am sorry. I searched and found the literatures. They only reported the compounds. K.Itoh et al., Chem.Pharm.Bull.,34,1128,2078,3747(1986). He presented only at the symposium about calculations. He used MM2 and extended Huckel to calculate CV3317 and cyclic compounds. They took X-ray structure of CV-3317, and found that the methyl group and indane ring is very near. Thus, he calculated 6-membered ring as 54kcal/mol, 7-membered ring as 0.8kcal/mol, 8- as 0.7, and 9- as -0.4. And at last they found CV-5975. ____/ ___/ ___/ Yoshihisa INOUE (^_^) the Green Cross Corp. / / / 2-25-1 Shodai-Ohtani,Hirakata,Osaka 573 JAPAN / _ / / / tel: +81-720-56-9328 / / / / fax: +81-720-68-9597 _____/ ____/ ____/ E-mail: inoue@greencross.co.jp ======================================================== Gange, D. M., S. Donovan, and K. Henegar "The Design of Insecticidal Uncouplers." 207th American Chemical Society National Meeting, San Diego, Calif., March 13-17, 1994 COMP 171 The discovery of the potent insecticide pyrrolomycin in 1985 led to an intensive study of the properties pf pyrrolomycin and related pyrrole insecticides. Mitochondrial assays indicated that the mode of action of the pyrroles was uncoupling. The compounds uncouple respiration from phosphorylation, preventing the synthesis of ATP. A QSAR model describing the activity of the pyrroles has been developed. The development of the model and the use of the model to predict the activity of a new class of uncouplers will be discussed. To contact the lead author, please send email to ganged@pt.Cyanamid.com --David Saari saarid@pt.Cyanamid.com ========================================================= One of the research scientists here at the American Cyanamid Company Agricultural Research Division successfully predicted the biological activity of a series of potentially commercial agrochemical compounds. I don't know how much of this research has been cleared for release to the public so I can't give details without checking to see if the research has been published or disclosed at a scientific meeting, etc., (patentability considerations, you know). In this case, I can say that the research was not a "black box" situation. The computational chemistry was a tool for predicting possible activity. Nevertheless, chemists did have to make the compounds, and our screening people had to run the tests to confirm biological activity. --David Saari saarid@pt.Cyanamid.COM ****************************************************************************** The 'classic' example you seek is Mark von Itzstein and Peter Colman's work on neurimidase inhibitors as anti-flu drugs. Their very first do novo inhibitor is in second stage trials and there are much better ones coming along behind. See the recent cover story in Nature. Dr. David A. Winkler D.Winkler@chem.csiro.au ******************************************************************************* About two or three years ago, Hoffmann-La Roche of Switzerland brought the first "designed" drug to the market. It is a drug that passes the blood/brain barrier, and is converted by an ezymatic reaction in the brain to the active compound. The pre- drug was modelled for that enzyme. As far as I know, the German chemical and pharmaceutical industries use Molecular Modelling extensively. following their demand, there have been several new position for computational chemistry professors founded during the past five years to teach students the basics of modelling. Dr. Rainer Stumpe INTERNET:STUMPE@SPINT.COMPUSERVE.COM ******************************************************************************* ........ Drug companies and other chemical manufacturers are not going to tell you about this even if they have an example. This type of stuff is usually proprietary. .......... How then should CC be viewed? I think an excellent analogy is the way we think about the analytical chemistry (AC) division of any large res- earch operation. AC supports efforts in all phases of the research process. However, the mass spec guy is never asked "What specific drug product is that there $500,000 GC/MS dohicky responsible for?" Everyone recognizes that the mass spec is part of the effort, and things would be crippled without it. This is how CC should be integrated into the research/discovery process. There are several models on how to include CC in a company's effort. In one, the CC guys are a consulting group that works with people that bring them specific problems. In another, each effort has one or more CC guys IN the group. Both are valid and both seem to be producing results. CC is good are predicting trends and in focusing experimental investigations, which are fairly expensive these days. CC should be part of every research problem in a modern setting. PART, I said, not WHOLE. Alot of the recent "backlash" against CC is due to overselling. If we CC folk expect to survive, we don't need to oversell the results that we can provide, but honestly point out what CC should be doing. To finish, I'll tell a little story. When I was interviewing for a job on leaving the Dewar group about 6 years ago, I visited the research labs of a large midwestern polymer manufacturer. I was shown a lab with 4 PhD polymer chemists in it. Each was required to make 1 new polymer blend per week. These blends then went to physical testing for evaluation as new products. The company expected to get one new CANDIDATE for a new product each year out of that lab. Seems a bit cost prohibitive doesn't it? They asked me how CC could help them. Back then, the answer was much less positive than it is now, but even then, CC could have helped them focus their efforts more directly and greatly enhanced the "hit rate." IMHO, that's what we do best. ........... Andy Holder University of Missouri - Kansas City || Internet Addr: aholder@vax1.umkc.edu ******************************************************************************** Hello, There are numerous examples of "designed" compounds that have biological activity. Unfortunately, many companies do not reveal this information. You should consult the December 1993 issue of Scientific American for a well written article by Charlie Bugg et al. Phil Bowen Computational Center for Molecular Structure and Design Department of Chemistry University of Georgia ******************************************************************************* Agouron Pharmaceuticals has published work on de novo design of inhibitors to thymidylate synthase; some of these inhibitors are in clinical trials. Ciba-Geigy and BioCryst have published work on de novo design of inhibitors of purine nucleoside phosphorylase; I think one of these may also be in trials. DuPont-Merck has a paper in press in Science describing their de novo design and crystallographic verification of a potent, nonpeptide HIV protease inhibitor. This compound is also in clinical trials. Jeff Blaney Chiron ******************************************************************************* Certainly all of the HIV-protease inhibitors fit into your category. Abbott has at least one in clinical trial. The big splash was the DuPont-Merck cyclic urea , but SmithKline also designed a similar compound. The former is in the clinic I think; I don't know about the latter. Additionally, the renin inhibitors were designed, usually from modeled structures. Alex Vlodower and John Erickson have a recent review on the HIV protease inhibitors. Yvonne Martin Abbott Laboratories There was also a recent ACS Satellite Symposium on the topic. >From MARTIN@CMDA ******************************************************************************* I'm not aware of those that have reached market or clinical trails but, there was a article about the process this year: J.Montgomery, S.Niwas, Structure Based Drug Design, CHEMTECH 23(11) November 1993, 30 Charles G James Chemistry Department University of North Carolina at Asheville. One University Heights Asheville, NC 28804-3299 Phone: 704-251-6443 james@unca.edu ******************************************************************************** There are a few examples which come close to being De novo designed, but I've olny heard these discussed at conferences (even these used a large amount of physical data in the models). A recent scientific american article should leed you in the right direction. Scientific American December 1993 Drugs by Design 92-98 C.E.Bugg W.M.Carson J.A.Montgomery Regards, Mike Miller ******************************************************************************* In the December 1993 issue of Scientific American, p.92 there is a good article "Drugs by Design." At the end of the article, p. 98, there are listed some drugs that were designed. I know that Agrouon's molecules are in Phase I trials, one in England and one in the States. They were developed from the tertiary structure of the enzyme in question. ****************************************************************************** > Hello, > > A while back someone asked about success stories in rational > drug design. In that light, what does the group think of the Merck > groups article in *Science* 23:380-384 where they rationally designed > inhibitors of HIV protease? > > Martin J. Gallagher phone: (617) 432-1729 > Dept. of Neurobiology fax: (617) 734-7557 > Harvard Medical School E-mail: marty@ionchannel.med.harvard.edu Background information: here at Washington University we developed a 3D-QSAR - CoMFA model for 59 HIV-protease inhibitors (see J Med Chem 36:4152-4160 1993) - a model that was based on experimentally derived alignment rules (crystals of 7 inhibitors) and was tested for predictive power (36 compounds with different chemistry - but peptides as the other 59) and explanatory power (CoMFA fields were compared and interpreted in the light of binding site residues in immediate contact with the inhibitors). The work on predictive power was submitted to J Med Chem, and the one on explanatory power is to be printed in Drug Design and Discovery. .......... The non-peptide cyclic ureas were announced at the Gordon Conference in QSAR (August 1993) where Dr Eyermann gave a lecture (no activities, though). The four compounds with published activities were predicted by our model as follows (see the Science paper for #s): Cmpd Actual Predicted (both as IC50, micromolar) 1 0.63 0.132 2 0.30 0.140 3 0.22 0.23 4 0.036 0.061 .......... Comments regarding the drug design tactics used by the DuPont-Merck group (or how did they 'set forth' to get advantages in the HIV-protease front): structural knowledge of the free enzyme and the inhibitor-bound enzyme was ESSENTIAL for this study, because specific targets were aimed at: * atoms in the binding site which were important in the economy of binding which were used to define the * 3D pharmacophore (exact location of binding site atoms - which are then used as template for putative structures that can match this pattern), which was then used as a query in a * 3D database search (useful concept: has anyone done such a compound before? - ... or how close to our 3D pattern are already-made-cmpds ?) this proves many times to be of help, but users are aware that such a method would not suggest NEW compounds, and this is where the molecular modeler (or was it a medicinal chemist?) uses knowledge blended with imagination to come with the * "_initial_idea_ for a nonpetide inhibitor that includes a structural water mimic" (exact quote) - this suggests that someone in the group came with this suggestion, upon which the work was continued later on, the skeleton was refined to ensure * better complementarity with the 3D pharmacophore (e.g., two hydroxyls instead of one, to bind two aspartates in the catalytic site, and the urea instead of the keto to improve electrostatic negative pattern in the flaps region for better hydrogen bonding) .......... The Science paper proves that current concepts used in drug design are valid - but it is quite clear that a scientist (or a team of scientists) is needed, because this problem was not solved entirely by a computer. However, the use of computational methods was essential. ========================== Tudor-Ionel Oprea = Tel. (1-314) 935 4672 = tudor@wucmd.wustl.edu = =============================================================== I don't have the results of the previous survey, but a few examples. All of these are in the clinic (or were). Not in any particular order. 1. the Agouron thymidilate synthase inhibitors 2. the Abbott C2 symmetric HIV protease inhibitors 3. the Biocryst/Ciba/Cornell PNP inhibitors 4. the Dupont-Merck HIV protease inhibitors 5. the Merck carbonic anhydrase inhibitor (will be on the market this year!) Finally, our HIV protease inhibitor, VX-478, should be in the clinic later this year. Hope this helps. / Mark (markm@vpharm.com) Cheers, Dave __________________________________________________________________________ Dr. David A. Winkler Voice: 61-3-542-2244 Principal Research Scientist Fax: 61-3-543-8160 CSIRO Division of Chemicals and Polymers Private Bag 10 Clayton, Australia. =========================================================================== I am not sure what the whole story is, but look into the story about ranitidine development by Sir James Black, who won the Nobel prize. The drug is for ulcers. Donald Doyle UNC Chemistry ============================================================================ I will point out 3 other references: Snyder, J. P. Med. Research Reviews, 11, 641-662, 1991 John Wiley and Sons, Inc. Navia, M. A. and Murcko, M. A. Current Opinion in Structural Biology 2, 202-210, 1992 Kuntz, I. D, Science 257, 1078-1082, 1992. Kent Stewart Abbott Laboratories ============================================================================= I am unaware of any commerically available drugs that have been design with the aid of computer modelling, however alot of work has been done on peptides and analodues of peptides as inhibitors of Angiotensin Converting Enzyme ACE. There have also been a number of studies of protease inhibitors, such as HIV Protease inhibitors using Sybil and the 3D crystal structures from data bases such as Brookhaven. Dr. Robert Wiley and......? have written a review article on the subject. Tim Volm tvolm.blue.weeg.uiowa.edu ============================================================================= One of the first from structure-based drug design will be Abbott's HIV protease inhibitor. The NDA has not been filed yet. It was designed & synthesized almost a decade ago, when the methods were much less robust. Most of the earlier designed compounds have failed for one of the usual reasons. This is true of our D1 dopaminergic agonists, first generation. @@@@@@@@@@@ Yvonne Martin, Senior Project Leader @ Computer Assisted Molecular Design Project @@@@@@@@ @ D-47E, AP10 2fl @ @ Abbott Laboratories @ @ 100 Abbott Park Road @@@@@@@@@@ Abbott Park, IL 60064-3500 Phone: 708 937-5362 FAX: 708 937-2625 ============================================================================= Has anyone mentioned the carbonic anhydrase inhibitor story? Merck developed a CAI drug for treatment of glaucoma using (among many other techniques!) structure-based drug design. This is the only example I know of that has actually been approved in the USA. ============================================================================ I hope this helps, Steven E. Schafer S.U.N.Y. Binghamton Chemistry Department http;//chemiris.chem.binghamton.edu:8080 Binghamton, New York USA From cmartin@rainbow.uchicago.edu Fri Mar 24 11:38:08 1995 Received: from midway.uchicago.edu for cmartin@rainbow.uchicago.edu by www.ccl.net (8.6.10/930601.1506) id LAA12996; Fri, 24 Mar 1995 11:28:20 -0500 Received: from rainbow.uchicago.edu (rainbow.uchicago.edu [128.135.136.33]) by midway.uchicago.edu (8.6.10/8.6.4) with SMTP id KAA26055 for <@midway.uchicago.edu:chemistry@ccl.net>; Fri, 24 Mar 1995 10:28:20 -0600 Received: by rainbow.uchicago.edu (931110.SGI/930416.SGI) for @midway.uchicago.edu:chemistry@ccl.net id AA21222; Fri, 24 Mar 95 10:27:43 -0600 From: cmartin@rainbow.uchicago.edu (Charles Martin) Message-Id: <9503241627.AA21222@rainbow.uchicago.edu> Subject: Sirius MCSCF To: chemistry@ccl.net Date: Fri, 24 Mar 1995 10:27:43 -0600 (CST) X-Mailer: ELM [version 2.4 PL24] Mime-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7bit Content-Length: 187 Netters, Does anyone know that status of the Sirius MCSCF program? Regards Charles Martin Theoretical Biophysics Beckman Institute The University of Illionis at Urbana-Champaign From xl@chem.UCSD.EDU Fri Mar 24 11:53:08 1995 Received: from mail.ucsd.edu for xl@chem.UCSD.EDU by www.ccl.net (8.6.10/930601.1506) id LAA13278; Fri, 24 Mar 1995 11:45:30 -0500 Received: from chem.chem.ucsd.edu by mail.ucsd.edu; id IAA15338 sendmail 8.6.11/UCSD-2.2-sun via SMTP Fri, 24 Mar 1995 08:45:28 -0800 for Received: by chem.chem.ucsd.edu (5.51) id AA22391; Fri, 24 Mar 95 08:43:56 PST Received: by checfs1 (5.0/UCSDPSEUDO.4) id AA27364 for CHEMISTRY@ccl.net; Fri, 24 Mar 1995 08:44:33 -0800 Date: Fri, 24 Mar 1995 08:44:33 -0800 From: xl@chem.UCSD.EDU (Xiping Long) Message-Id: <9503241644.AA27364@checfs1> To: CHEMISTRY@ccl.net Cc: xl@checfs1.UCSD.EDU Subject: MOPAC for Cray T3D Content-Length: 257 Hi, Everyone, Does anyone know if there exists a version of MOPAC or other semiempirical codes parallelized for Cray T3D? Cray Research has one but it works only on a single PE so far. Your information is very much appreciated. Best regads. Xiping Long From pavan@daffy.bnpi.com Fri Mar 24 12:53:08 1995 Received: from beavis.bnpi.com for pavan@daffy.bnpi.com by www.ccl.net (8.6.10/930601.1506) id MAA14554; Fri, 24 Mar 1995 12:51:34 -0500 From: Received: from daffy.bnpi.com by beavis.bnpi.com (AIX 3.2/UCB 5.64/4.03) id AA21377; Fri, 24 Mar 1995 11:45:58 -0600 Received: by daffy.bnpi.com (AIX 3.2/UCB 5.64/4.03) id AA15872; Fri, 24 Mar 1995 11:45:57 -0600 Date: Fri, 24 Mar 1995 11:45:57 -0600 Message-Id: <9503241745.AA15872@daffy.bnpi.com> To: chemistry@ccl.net Subject: looking for curve fitting program Hello, Everyone I am looking for a curve fitting program. Could somebody tell me where I can get one? Thanks for your help. pavan e.mail pavan@bnpi.com From COYY@UNB.CA Fri Mar 24 13:38:09 1995 Received: from unb.ca for COYY@UNB.CA by www.ccl.net (8.6.10/930601.1506) id NAA15317; Fri, 24 Mar 1995 13:33:24 -0500 Received: from UNBVM1.CSD.UNB.CA by unb.ca (8.6.10/950316-15:25) id OAA02207; Fri, 24 Mar 1995 14:33:10 -0400 Received: from UNBVM1.CSD.UNB.CA by UNBVM1.CSD.UNB.CA (IBM VM SMTP V2R2) with BSMTP id 8226; Fri, 24 Mar 95 13:55:54 AST Received: from UNB.CA (NJE origin MUSIC@UNBVM1) by UNBVM1.CSD.UNB.CA (LMail V1.2a/1.8a) with BSMTP id 8225; Fri, 24 Mar 1995 13:37:59 -0400 Message-Id: <24MAR95.14715404.0249.MUSIC@UNB.CA> Date: Fri, 24 Mar 95 13:37:31 -0400 From: COY To: Subject: CCL: Conference Announcement X-Mailer: MUSIC/SP V3.1.1 12th Canadian Symposium on Theoretical Chemistry 12i me Symposium Canadien sur la Chimie Thorique Fredericton, 6-11 August/Aot 1995 Co-chairmen: William J. Meath and Ajit J. Thakkar The 12th Canadian Symposium on Theoretical Chemistry will be held August 6-11, 1995 at the Wu Conference Centre, University of New Brunswick, Fredericton, NB, under the co-chairmanship of William J. Meath (University of Western Ontario) and Ajit J. Thakkar (University of New Brunswick). The program will include invited papers and contributed posters in all areas of theoretical chemistry. The topics selected for emphasis are: * Structure, properties and dynamics of weakly interacting systems * Condensed phases from clusters to solids and from dynamics to bulk properties * Laser-molecule interactions: dynamics to spectroscopy * Kinetics and reaction dynamics * Molecular properties * Surfaces and interfaces * Materials design * Computer simulation and statistical mechanics * Quantum chemistry: methods and applications * Novel computational and mathematical techniques * Biochemical systems Invited Speakers Invited Speakers Session chairs J.M. Andre (Belgium) J.N. Murrell (England) R.J. Boyd A.D. Bandrauk (Canada) J. Oddershede (Denmark) T. Carrington, Jr. R.J. Bartlett (U.S.A.) S.D. Peyerimhoff (Germany) R.S. Dumont D.M. Bishop (Canada) P. Pyykko (Finland) I.P. Hamilton P. Botschwina (Germany) H.A. Rabitz (U.S.A.) W.G. Laidlaw P.W. Brumer (Canada) M.A. Ratner (U.S.A.) T.T. Nguyen-Dang D. Ceperley (U.S.A.) A. Rauk (Canada) J. Paldus E.R. Davidson (U.S.A.) S.A. Rice (U.S.A.) G.N. Patey C.E. Dykstra (U.S.A.) D.R. Salahub (Canada) R.A. Poirier J.T. Hynes (U.S.A.) P. Saxe (U.S.A.) S.M. Rothstein B. Jeziorski (Poland) H.A. Scheraga (U.S.A.) B.C. Sanctuary W.L. Jorgensen (U.S.A.) K.C. Showalter (U.S.A.) V.H. Smith, Jr. R.E. Kapral (Canada) J. Simons (U.S.A.) S.G. Whittington H.J. Kreuzer (Canada) D.W. Sumners (U.S.A.) J.S. Wright R.J. LeRoy (Canada) D.G. Truhlar (U.S.A.) M.C. Zerner W. Meyer (Germany) D.M. Wardlaw (Canada) T. Ziegler P.G. Mezey (Canada) K.B. Whaley (U.S.A.) W.H. Miller (U.S.A.) W. Yang (U.S.A.) D.J. Moore (Switzerland) Contributed papers are welcome in all areas of theoretical chemistry. All contributed papers will be given in poster format. For registration forms, contact the Conference Secretary, 12th CSTC, Department of Chemistry, University of New Brunswick, Fredericton, NB E3B 6E2, Canada. Fax: 506-453-4981. Internet: coyy@unb.ca From arne@hodgkin.mbi.ucla.edu Fri Mar 24 20:38:12 1995 Received: from hodgkin.mbi.ucla.edu for arne@hodgkin.mbi.ucla.edu by www.ccl.net (8.6.10/930601.1506) id UAA24182; Fri, 24 Mar 1995 20:27:32 -0500 Received: by hodgkin.mbi.ucla.edu; id AA26350; Fri, 24 Mar 1995 17:33:58 -0800 Message-Id: <9503250133.AA26350@hodgkin.mbi.ucla.edu> To: walkerd@sask.usask.ca Cc: chemistry@ccl.net Subject: Re: CCL:Molecular Modeling Packages for ALPHA systems Reply-To: arne@hodgkin.mbi.ucla.edu In-Reply-To: Your message of "Wed, 22 Mar 1995 10:52:51 -0600 (CST)" References: <01HOFMUU7QMQ8WXD2W@SKYCAT.USask.CA> X-Mailer: Mew beta version 0.89 on Emacs 19.28.0.1 Mime-Version: 1.0 Content-Type: Text/Plain; charset=us-ascii Date: Fri, 24 Mar 95 17:33:58 -0800 From: "Arne Eofsson (arne@uclaue.mbi.ucal.edu)" X-Mts: smtp I think Quanta form MSI and Midas (cheap) from UCSF runs on the alphas. Sorry I do not have the adresses. arne From hugo@montara.molres.org Fri Mar 24 20:41:26 1995 Received: from mail.barrnet.net for hugo@montara.molres.org by www.ccl.net (8.6.10/930601.1506) id UAA24177; Fri, 24 Mar 1995 20:27:13 -0500 Received: from montara.molres.org. by mail.barrnet.net (8.6.10/BARRNET-Len-Rose) id RAA19499; Fri, 24 Mar 1995 17:27:10 -0800 Received: by montara.molres.org. (4.1/SMI-4.1) id AA05634; Fri, 24 Mar 95 17:29:22 PST Date: Fri, 24 Mar 95 17:29:22 PST From: hugo@montara.molres.org (Hugo Villar) Message-Id: <9503250129.AA05634@montara.molres.org.> To: chemistry@ccl.net Subject: Mulliken Hi, Can someone give me information about the package Mulliken? Has anyone seen a demo of this program?. How would you rate it compare4d to other similar packages?. If there is enough interest, I will sumarize... Thanks! Hugo O. Villar