From chemistry-request@server.ccl.net Wed Sep 8 04:42:55 1999 Received: from pythie.natur.cuni.cz (pythie.natur.cuni.cz [195.113.59.127]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id EAA11483 for ; Wed, 8 Sep 1999 04:42:53 -0400 Received: from natur.cuni.cz (localhost [127.0.0.1]) by pythie.natur.cuni.cz (980427.SGI.8.8.8/980728.SGI.AUTOCF) via ESMTP id BAA39120 for ; Wed, 8 Sep 1999 01:39:30 -0700 (PDT) Sender: sopko@natur.cuni.cz Message-ID: <37D620BF.37BEECF4@natur.cuni.cz> Date: Wed, 08 Sep 1999 01:39:28 -0700 From: Bruno Sopko Reply-To: sopko@natur.cuni.cz X-Mailer: Mozilla 4.05C-SGI [en] (X11; I; IRIX 6.5 IP32) MIME-Version: 1.0 To: chemistry@ccl.net Subject: LINUX and Autodock 3 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit Is there, please, anybody, who succesfully compiled Autodock 3.0on LINUX machine? I am having problems with the autotors programme. Thank you Bruno Sopko sopko@natur.cuni.cz From chemistry-request@server.ccl.net Tue Sep 7 18:50:56 1999 Received: from canter-n-siegel.schrodinger.com (canter-n-siegel.schrodinger.com [192.156.98.248]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id SAA08835 for ; Tue, 7 Sep 1999 18:50:56 -0400 Received: (from info@localhost) by canter-n-siegel.schrodinger.com (8.8.5/8.8.5) id PAA12467 for chemistry@ccl.net; Tue, 7 Sep 1999 15:47:05 -0700 Date: Tue, 7 Sep 1999 15:47:05 -0700 From: Schrodinger Info account Message-Id: <199909072247.PAA12467@canter-n-siegel.schrodinger.com> To: chemistry@ccl.net Subject: Titan Now Shipping Schrodinger and Wavefunction jointly announce the release of Titan, which seamlessly integrates the high performance computations of Jaguar and the visualization and ease-of-use of Spartan. Titan allows any chemist to: - Construct complex organic, organometallic and inorganic molecules. Obtain transition states from an extensive reaction database. - Perform calculations with a wide range of computational methods including molecular mechanics, semi-empirical methods, Hartree-Fock, DFT, and LMP2. Pseudospectral techniques make Titan 2-4 times faster than conventional programs for Hartree-Fock and density functional calculations and 1-2 orders of magnitude faster for LMP2 calculations (when compared to conventional MP2 calculations). - Display multiple model styles. Calculate properties, volumes and surface areas. Present dramatic 3D isosurface and 2D slice displays of electronic properties. Organize and analyze results in a spreadsheet. - Drive coordinates to simulate chemical reactions, search conformation space, determine equilibrium and transition-state geometries, and evaluate normal-mode vibrational frequencies. For more information, or to request a demo CD, please contact us at: Wavefunction, Inc. Schrodinger, Inc. (949)955-2120 (503)299-1150 (949)955-2118 fax (503)299-4532 fax sales@wavefun.com sales@schrodinger.com http://www.wavefun.com http://www.schrodinger.com From chemistry-request@server.ccl.net Tue Sep 7 19:39:51 1999 Received: from ccl.net (atlantis.ccl.net [192.148.249.4]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id TAA09531 for ; Tue, 7 Sep 1999 19:39:51 -0400 Received: from mercury.chem.csiro.au (mercury.chem.CSIRO.AU [138.194.50.8]) by ccl.net (8.8.6/8.8.6/OSC 1.1) with ESMTP id TAA26039 for ; Tue, 7 Sep 1999 19:35:54 -0400 (EDT) Received: from [138.194.46.107] (cpr-46107.chem.csiro.au [138.194.46.107]) by mercury.chem.csiro.au (8.9.1/8.9.1) with ESMTP id JAA20316; Wed, 8 Sep 1999 09:34:10 +1000 (EST) X-Sender: win097@mail.chem.csiro.au (Unverified) Message-Id: In-Reply-To: <37D4FCC1.40AF6E5E@stark.udg.es> Mime-Version: 1.0 Content-Type: text/enriched; charset="us-ascii" Date: Wed, 8 Sep 1999 09:35:25 +1000 To: "Computational Chemistry List (CCL)" From: "Dr. Dave Winkler" Subject: Re: CCL:cross-validation and prediction with PLS Cc: David Robert > >A requisite for the data is to be standardized (mean zero, sdv one). To >check the statistical significance of a predictive model the >leave-one-out (LOO) cross-validation is usually performed. When a >molecule is removed, a new standardization needs to be computed for the >remaining n-1 compounds, and the new mean and sdv will be applied to the >extracted molecule. However, for the usual sample sizes (n=30 to 150) >the error committed in equalling the mean/sdv for the n-1 and n >molecules is not neglectable, and it clearly affects the results of the >prediction for the removed molecule. The same can be said about the >prediction of the property for a test set: the mean/sdv of the training >set QSAR model will be applied to the test set in order to have >standardized descriptors, but the mean/sdv if we included all the >molecules (training+test) may be very different. There are a whole raft of problems which arise with cross-validation and testing, for example: 1. What is the best way to chose a validation set (or test for that matter) is leave-one-out, leave-N-out etc? 2. Should clustering be used to choose a representative test set and , if so, what kind of clustering algorithm and do you cluster on X, Y or X/Y? 3. Effort involved in the cross validation process scales as the square of the number of compounds and the square of the number of independent variables, which has important implications for large data sets (eg combichem/HTS data) 4. Once a cross validation process has been completed, there are N QSAR models, all slightly different. Which is the 'best' or 'true' model? 5. What statitical methods should be used to choose the 'best' model? 6. How do you avoid overfitting? My colleague, Frank Burden (Monash University) and I have used Bayesian regularized neural nets for QSAR. We find that they overcome virtually all of the problems with PLS QSAR models as they give the single statistically best model possible for the data set. In addition there are good theoretical reasons why they do not require cross validation or test sets. We are investigating this for QSAR and preliminary results suggest that this is the case. We have published some of this work recently: [74] New QSAR Methods Applied to Structure-Activity Mapping and Combinatorial Chemistry, Burden, F.R. and Winkler, D.A. J. Chem. Inf. Comput. Sci. 39, 236 (1999). [75] The Computer Simulation of High Throughput Screening of Bioactive Molecules, F.R. Burden, D.A. Winkler, in Molecular Modelling and Prediction of Bioactivity (K. Gundertofte and F.S. Jorgensen eds), Plenum Press 1998. [80] Robust QSAR Models Using Bayesian Regularised Artificial Neural Networks, Burden, F.R. and Winkler, D.A. J. Med. Chem., 1999; 42(16); 3183-3187 (1999). [81] A QSAR Model for the Acute Toxicity of Substituted Benzenes towards Tetrahymena Pyriformis using Bayesian Regularized Neural Networks. F R. Burden* David A. Winkler, Chem. Res. Toxicol., in press. [82] Robust QSAR Models from Novel Descriptors and Bayesian Regularized Neural Networks, Winkler, D.A, Burden, F.R. Mol. Simul. 1999 in press. [87] Do QSAR Models using Bayesian Regularized Artificial Neural Networks Really Need Validation? Winkler, D.A. and Burden, F.R. J.Chem. Inf. Comput. Sci in preparation. Cheers, Dave Dr. David A. Winkler Email: dave.winkler@molsci.csiro.au Senior Principal Research Scientist Voice: 61-3-9545-2477 CSIRO Molecular Science Fax: 61-3-9545-2446 Private Bag 10,Clayton South MDC 3169 http://www.csiro.au Australia http://www.molsci.csiro.au From chemistry-request@server.ccl.net Wed Sep 8 06:45:01 1999 Received: from uscmail.usc.es (uscmail.usc.es [193.144.75.8]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id GAA11919 for ; Wed, 8 Sep 1999 06:44:55 -0400 Received: from qogolem (qogolem.usc.es [193.144.74.235]) by uscmail.usc.es (8.9.1/8.9.1) with SMTP id MAA17671 for ; Wed, 8 Sep 1999 12:40:36 +0200 (MET DST) From: "Armando Navarro" To: Subject: Summary:printing cas configurations Date: Wed, 8 Sep 1999 12:40:32 +0200 Message-ID: <01bef9e6$93bf3a90$eb4a90c1@qogolem.usc.es> Some time ago I asked the list about how to print the weight of all configurations in cas calculations with g98. I received several answers, but the right one was from Douglas Fox: Prof. Navarro, This is not a parameter which can be adjusted from the input. It prints upto the first 50 most important configurations in order of magnitude. If you have source you can change this and recompile but this is not possible with the G98W product.=20 Douglas J. Fox Technical Support Gaussian, Inc. help@gaussian.com Thanks to all the people who answered my question Armando Navarro Departamento de quimica organica Facultade de quimica Universidade de Santiago de Compostela e-mail qoajnv@usc.es From chemistry-request@server.ccl.net Wed Sep 8 09:54:43 1999 Received: from ccl.net (atlantis.ccl.net [192.148.249.4]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id JAA13382 for ; Wed, 8 Sep 1999 09:54:42 -0400 Received: from ns02.sbphrd.com (firewall-user@ns02.sbphrd.com [208.198.64.2]) by ccl.net (8.8.6/8.8.6/OSC 1.1) with SMTP id JAA09974 for ; Wed, 8 Sep 1999 09:50:37 -0400 (EDT) From: ryanmd@mh.us.sbphrd.com Received: by ns02.sbphrd.com; id JAA05415; Wed, 8 Sep 1999 09:49:28 -0400 Received: from unknown(139.136.64.5) by ns02.sbphrd.com via smap (V5.0) id xma005365; Wed, 8 Sep 99 09:49:18 -0400 Received: from phu847.um.us.sbphrd.com (phu847.um.us.sbphrd.com [139.136.98.147]) by phinet.sbphrd.com (8.9.1b+Sun/8.9.1) with ESMTP id JAA05855; Wed, 8 Sep 1999 09:50:14 -0400 (EDT) Received: (from ryanmd@localhost) by phu847.um.us.sbphrd.com (8.8.8/8.8.8) id NAA249308; Wed, 1 Sep 1999 13:56:40 -0400 (EDT) Date: Wed, 1 Sep 1999 13:56:40 -0400 (EDT) Message-Id: <199909011756.NAA249308@phu847.um.us.sbphrd.com> To: CCL , QSAR Society , han_waterbeemd@sandwich.pfizer.com, Roger Lahana Subject: Re: CCL:FW: Drug-like inactive molecules References: I think the idea is an interesting one, particularly of benefit to a company with statistical tools to infer subsets of data that might lead to heuristics, such as your company. I question the value of the data in the absence of enough positives however. The ability to discern rules, either by decision trees or by another qsar-like system would seem to be far less 'bounded' than one which is driven by the actual hits. Related then to this is the problem of relating the definition of a hit across different screens, let alone different companies or academics. HTS is usually +/- and threasholds are frequently different. In addition, compounds that are directly assayed by one group often have activities differing by an order of magnitude or more when assayed by another group. There are often normalizing compounds, but sometimes not and sometimes there is just that much noise. Without big pharma databases to reduce the noise, I would question the possibility of useful conclusions arising. Is there an estimate of the number of compounds screened in strictly non-commercial enterprises as compared with the total number of compounds screened by the pharmaceutical companies and 'near-pharma' companies such as startups with a special chemistry hook or even academics that have discovered a commercial interest? I would hazard a guess that the commercial side is on the order of 20-50M compounds (including combi-libs actually synthesized and tested) and academics 100K-1M. I do not really know the number though. __ M. Dominic Ryan (610)-270-6529 SmithKline Beecham Pharmaceuticals Internet: ryanmd@mh.us.sbphrd.com King of Prussia, PA From chemistry-request@server.ccl.net Wed Sep 8 15:08:03 1999 Received: from schrodinger.com (root@thermidore.schrodinger.com [192.156.98.99]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id PAA14838 for ; Wed, 8 Sep 1999 15:08:02 -0400 Received: from tandoori.schrodinger.com (tandoori.schrodinger.com [166.84.149.99]) by schrodinger.com (8.8.5/8.8.5) with ESMTP id MAA12574 for ; Wed, 8 Sep 1999 12:03:58 -0700 Received: from avarice (hazel.schrodinger.com [166.84.149.150]) by tandoori.schrodinger.com (8.8.5/8.8.5) with SMTP id PAA20477 for ; Wed, 8 Sep 1999 15:03:27 -0400 From: "Hege S. Beard" To: Subject: Schrodinger Seminar Series in Europe Date: Wed, 8 Sep 1999 15:02:44 -0400 Message-ID: <001c01befa2c$bb432f40$969554a6@avarice.schrodinger.com> MIME-Version: 1.0 Content-Type: text/plain; charset="iso-8859-1" Content-Transfer-Encoding: 8bit X-Priority: 3 (Normal) X-MSMail-Priority: Normal X-Mailer: Microsoft Outlook 8.5, Build 4.71.2173.0 X-MimeOLE: Produced By Microsoft MimeOLE V4.72.3110.3 Importance: Normal Dear Colleague, Please mark your calendar! Schrödinger will be hosting a series of seminars in Europe (London, Paris, Frankfurt, Munich), September 20-24, 1999. The seminars will feature talks by: Professor Richard A. Friesner Columbia University, New York and Professor William A. Goddard* California Institute of Technology, California The presentations will concentrate on recent scientific studies, and focus on how computational tools have been used in solving a variety of problems in the areas of Chemical, Biological, and Materials sciences. Take advantage of this opportunity to meet colleagues, to discuss applications, and to learn more about Schrödinger's vision for future software development. For more information and registration for the seminars, please visit our web-site (www.schrodinger.com), or contact Dr. Hege S. Beard either by phone (1-201-433-2014 x101), fax (1-201-433-2065), or e-mail (hege@schrodinger.com). There is no registration fee for any of the seminars, and a light lunch will be served to participants. So, sign up for a meeting near you today, and join us for a day of science! We look forward to seeing you in Europe! * Professor William A. Goddard will unfortunately not be able to join us for the seminar in London. From chemistry-request@server.ccl.net Wed Sep 8 20:41:24 1999 Received: from ccl.net (atlantis.ccl.net [192.148.249.4]) by server.ccl.net (8.8.7/8.8.7) with ESMTP id UAA16407 for ; Wed, 8 Sep 1999 20:41:24 -0400 Received: from unomail.unomaha.edu (unomail.unomaha.edu [137.48.1.6]) by ccl.net (8.8.6/8.8.6/OSC 1.1) with SMTP id UAA29146 for ; Wed, 8 Sep 1999 20:37:12 -0400 (EDT) From: Douglas_Stack/CAS/UNO/UNEBR@unomail.unomaha.edu Received: by unomail.unomaha.edu(Lotus SMTP MTA v4.6.4 (830.2 3-23-1999)) id 862567E7.0002DC27 ; Wed, 8 Sep 1999 19:31:14 -0500 X-Lotus-FromDomain: UNIVERSITY OF NEBRASKA To: CHEMISTRY@www.ccl.net Message-ID: <862567E7.0002DA07.00@unomail.unomaha.edu> Date: Wed, 8 Sep 1999 19:31:07 -0500 Subject: Experiments using MM Mime-Version: 1.0 Content-type: text/plain; charset=us-ascii Content-Disposition: inline Dear CCLers, In developing a molecular modeling course, I am looking for experiments that will expand on molecular mechanics calculations into the biochemistry area. Specifically, after two labs of introduction to force fields and the components that determine energy, minimization, etc., I'd like to have a lab that displays how molecular mechanics is used to predict guest/host interactions of a protein or DNA sequence. We will be purchasing MacroMol as our primary molecular mechanics package. What I am looking for are articles involving a simple example of relatively large biomolecules and their interactions with each other. Other possible topics could involve the following: 1) display of molecular dynamics, i.e. the conformations possible to a protein at room temp and how one particular conformation may be responsible for biological activity 2) intercalation of a molecule into the base stacking of DNA 3) the effects of amino acid sequence on the conformation of a protein 4) docking of a ligand into an active site. My use of molecular modeling is mainly quantum calculation on small organic compounds, thus these topics are a bit foreign to me. Any J. Chem. Ed. articles would be ideal. Thanks for your time, I be sure to summarize the responses. Douglas E. Stack Assistant Professor Department of Chemistry University of Nebraska at Omaha Omaha, NE 68182-0109 (402) 554-3647 (402) 544-3888 (fax) destack@unomaha.edu