From chemistry-request@ccl.net Mon Jan 5 08:19:27 2004 Received: from bonito.ulb.ac.be (bonito.ulb.ac.be [164.15.59.220]) by server.ccl.net (8.12.8/8.12.8) with ESMTP id i05DItX9032004 for ; Mon, 5 Jan 2004 08:18:56 -0500 Received: from mach.vub.ac.be (mach.ulb.ac.be [164.15.128.3]) by bonito.ulb.ac.be (8.8.8/3.17.1.ap (resu)) id OAA14069; Mon, 5 Jan 2004 14:17:26 +0100 (MET) for Received: from algcpc10 (algcpc10.vub.ac.be [134.184.24.160]) by mach.vub.ac.be (8.9.3/3.13.5.aejp (mach)) id OAA19963; Mon, 5 Jan 2004 14:18:53 +0100 (MET) for From: "Giju Thomas Kalathingal" To: Cc: Subject: Summary: Calculations without Born-Oppenheimer approximation "2nd Call" Date: Mon, 5 Jan 2004 14:14:02 +0100 Message-ID: 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 IMO, Build 9.0.2416 (9.0.2911.0) X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2600.0000 Importance: Normal X-Spam-Status: No, hits=-0.9 required=7.0 tests=MSGID_GOOD_EXCHANGE,ORIGINAL_MESSAGE version=2.55 X-Spam-Checker-Version: SpamAssassin 2.55 (1.174.2.19-2003-05-19-exp) Hello everybody, Following is a listed summary for my question to CCL. Thanks for all the responses that helped me to get updated on recent developments. However, a program package that explicitly realise my querry is not yet available. Hope the summary helps CCLers. Wish you all a very successful 2004. Sincerely, Giju Kalathingal -----Original Message----- On Tue, 16 Dec 2003 15:11:47 +0100 (MET) Giju Kalathingal wrote: > Last week I had send the following message without > any success. So I am posting it again. > > Dear CCL-all, > > Could you please give me some info on programs > that let me to do quantum chemical calculations > (geometry optimzations and vibrational frequencies) > without Born-Oppenheimer approximation? > > Thanks in advance. > > Giju Kalathingal > ---------------------------------------------------------------------------- ---- Perhaps the reason you did not get any response was because your question specifically dealt with programs for geometry optimzations and vibrational frequencies. These concepts (molecular geometry and molecular vibrations) are normally understood within the Born-Oppenheimer approximation. I do not know of any readily available programs that deal with these outside of BO. However quantities such as bond lengths and vibrational frequencies are derivable from experiment and thus these concepts ARE defined beyond the Born-Oppenheimer approximation: equilibrium bond lengths, for instance, would be defined as the peaks in the two-particle radial distribution functions for the two bonded nuclei. See the special issue of Israel Journal of Chemistry, vol.19 (1980) for many papers (and much debate), e.g. those of R.G.Woolley, pp.30-46 and of Carl Trindle, pp.47-53. L. Lathouwers and P. Van Leuven (CPL 52, 439, 1977; PRA 18, 2150, 1978; IJQC S12, 371, 1978) demonstrated that the generator coordinate method could be employed to avoid the BO separation and develop a non-adiabatic formulation of molecular quantum theory. In a series of pioneering papers on hydrides (CPL 3, 705, 1969; PS 185, 90, 1969; PRA 2, 728, 1200, 1675, 1970; PRA 3, 565, 1022, 1971; PRA 4, 457, 1971; PRA 5, 1104, 1972), I.L.Thomas put electrons into electronic orbitals and protons into protonic orbitals (thereby avoiding the BO approximation), antisymmetrized the two kinds of orbitals separately, performed SCF computations and obtained molecular structures and spectra that corresponded to experiment. For instance, the microwave transition frequency of ammonia (conventionally explained by "umbrella flipping" between two structures) is now obtained as the transition frequency between protonic orbitals. Subsequently Thomas went on to become vice-president of Occidental Petroleum and did not continue his protonic structure studies. I wrote some programs to do similar computations as part of my candidacy work at Stony Brook in the early 80s, but those are now lost on some magnetic tape somewhere. There are now several computations and programs that go beyond the BO approximation by calculating the nonadiabatic coupling terms or performing a diabatic transformation in multi-reference CI or CASSCF spaces (see e.g. D.R.Yarkony in "Modern Electronic Structure Theory" Part I, World Scientific, Singapore, 1995, pp.642-721; W.Domcke, et al. CPL 216,362, 1993; 226, 257, 1994; Neuheuser, Sukumar and Peyerimhoff, Chem.Phys., 194, 45-64, 1995; Mol.Phys. 95, 61-70, 1998) but none of these can be considered as truly "without Born-Oppenheimer approximation" (PRA=Phys.Rev A; CPL=Chem.Phys.Lett.; IJQC=Int.J.Quantum Chem) N. Sukumar RPI Department of Chemistry ---------------------------------------------------------------------------- ---- I'm not really sure there IS an answer to your question. For one thing, I'm not even sure how "geometry optimization" would be defined without invoking the Born-Oppenheimer approximation. For another, I'm unaware of a computational chemistry program that doesn't use this approximation. --David Shobe, Ph.D., M.L.S. S|d-Chemie, Inc. phone (502) 634-7409 fax (502) 634-7724 ---------------------------------------------------------------------------- ---- Off hand I don't know of any, but I would be most interested in hearing of such codes. Could you summarize the replies please? All the best Laurence Cuffe ---------------------------------------------------------------------------- ---- Hello, I guess you are not going to be very succesful on getting answers because going past B-O for more than 3 body problems is not a solved problem yet. Good Luck esguerra!at!rci.rutgers.edu ---------------------------------------------------------------------------- ---- Along the lines of Dr Sukumar's response, one can do optimizations/frequencies via energy points utilizing BO-based energies corrected via the Born-Oppenheimer Diagonal Correction (BODC/DBOC), which will at least be one step closer to "non-Born-Oppenheimer" geometries/frequencies. Psi 3.2 (www.psicode.org) could be made to do this (using a DBOC based on SCF or CISD wavefunctions), though currently such an approach could not be carried out automatically. Steven Wheeler ---------------------------------------------------------------------------- ---- That brings up an interesting question (interesting for me anyway). What Dr. Sukumar defined below is AFAIK neither r-sub-e as it's usually defined within the Born-Oppenheimer approximation (i.e. the internuclear distance with minimum electronic energy), nor r-sub-zero which is the *mean* of the the two-particle radial distribution function. The definition below is the *mode* of the distribution. Dr. N. SUKUMAR wrote: "equilibrium bond lengths, for instance,would be defined as the peaks in the two-particle radial distribution functions for the two bonded nuclei" There are experimentally determined r-sub-e's, for example in the NIST Webbook databases. Is this the definition of r-sub-e used by experimentalists? It wouldn't necessarily be equal to r-sub-e as defined by computational chemists using the Born-Oppenheimer approximation, but one could argue that this is the result of using an approximation, and not that there are two different parameters called r-sub-e. --David Shobe ---------------------------------------------------------------------------- ---- The mean of the two-particle radial distribution function is not a meaningful quantity. Note that when you solve for the eigenfunctions of the Hamilronian WITHOUT making the Born-Oppenheimer separation, you do NOT get solutions corresponding to a particular molecular structure or isomer; you get a wave function which corresponds to ALL isomers of that stoichiometry. Thus the two-particle distribution function for C6H6 will have peaks corresponding to benzene, cyclobutadiene, prismane, bicyclo-propenyl, etc. The mean of these structures makes no sense chemically. In making the correspondance between the peaks (mode) of the two-particle radial distribution functions and equilibrium bond lengths, one makes the assumption that the low-energy regions of the potential energy hypersurfaces will be more populated in a canonical ensemble and thus will correspond to maxima in the distribution function. This follows equally > from Boltzman or Fermi-Dirac/Bose Einstein statistics for the nuclei. These would then correspond to low-temperature experimental structures. For high-temperature structures or highly fluxional molecules, of course, this simple correspondance with experiment will not hold. N. Sukumar RPI Department of Chemistry ---------------------------------------------------------------------------- ---- Am I incorrect that floating spherical gaussian codes [though having far less than optimal basis sets] can do this? John McKelvey ---------------------------------------------------------------------------- ---- FSGOs are basis functions; but for expanding WHAT? If you're expanding the ELECTRONIC wavefunction, you're firmly within BO. If you're expanding the TOTAL wavefunction, you have just the kind of situation I described. N. Sukumar RPI Department of Chemistry http://www.drugmining.com/ ---------------------------------------------------------------------------- ---- From chemistry-request@ccl.net Mon Jan 5 03:50:10 2004 Received: from sainfoin.extra.cea.fr (sainfoin.extra.cea.fr [132.166.172.103]) by server.ccl.net (8.12.8/8.12.8) with ESMTP id i058ncX9022137 for ; Mon, 5 Jan 2004 03:49:38 -0500 Received: from cincidele.saclay.cea.fr (cincidele.saclay.cea.fr [132.166.192.111]) by sainfoin.extra.cea.fr (8.12.10/8.12.9/CEAnet-Internet.2.0) with ESMTP id i058nblW013943 for ; Mon, 5 Jan 2004 09:49:37 +0100 (MET) Received: from nenuphar.saclay.cea.fr (unverified) by cincidele.saclay.cea.fr (Content Technologies SMTPRS 4.3.12) with ESMTP id ; Mon, 5 Jan 2004 09:37:04 +0100 Received: from CHRONO.saclay.cea.fr (chrono.intra.cea.fr [132.166.189.105]) by nenuphar.saclay.cea.fr (8.12.10/8.12.9/CEAnet-Internet.2.0) with ESMTP id i058najT005920; Mon, 5 Jan 2004 09:49:36 +0100 (MET) Received: by chrono.intra.cea.fr with Internet Mail Service (5.5.2653.19) id ; Mon, 5 Jan 2004 09:47:39 +0100 Message-ID: <3808A7D2DCEAD6118B63009027287265014AB2!at!azurite.saclay.cea.fr> From: VITORGE Pierre 094605 To: "'Jaroslaw Panek'" , chemistry!at!ccl.net Subject: RE: when to take a logarithm of biological activity in QSAR studi es? Date: Mon, 5 Jan 2004 09:49:34 +0100 MIME-Version: 1.0 X-Mailer: Internet Mail Service (5.5.2653.19) Content-Type: text/plain; charset="iso-8859-1" X-Spam-Status: No, hits=0.0 required=7.0 tests=none version=2.55 X-Spam-Checker-Version: SpamAssassin 2.55 (1.174.2.19-2003-05-19-exp) Content-Transfer-Encoding: 8bit X-MIME-Autoconverted: from quoted-printable to 8bit by server.ccl.net id i058oBX9022147 log(copncentration) is used because it is related to (macroscopic) thermodynamic chemical potential, mu: mu = mu0 + RT ln(activity) (this equation is the definition of chemical activity) and a good approximation of this activity is concentration (typically for dilute solutions). Chemical potential, mu, is Gibbs energy, G, for 1 mole (it is its definition). From delta_G of reaction and usual thermodynamics, mass action law is demonstrated, for reaction A + B -> C it is K = [C] / ([A] [B]) where [X] is the concentration of chemical species X, delta_G = -RT lnK = mu0(C) - mu0(A) - mu0(B) in reaction A + B -> C A, B and C can actually be any entity for which a chemical potential can be defined. It is typically used for "sorption sites", it can very well be used for binding sites of macromolecules Pierre Vitorge CEA DEN Saclay DPC/SECR/LSRM & UMR 8587 (CEA-Universite d'Evry-CNRS) Bat.391 Pe.40a 91191 Gif sur Yvette cedex France tel.(+33) 169-08-32-65, secr.: (+33)169-08-32-50, fax:(+33)169-08-32-42 http://perso.club-internet.fr/vitorgen/pierre -----Message d'origine----- De : Jaroslaw Panek [mailto:jarek!at!elrond.chem.uni.wroc.pl] Envoyi : mardi 30 dicembre 2003 13:02 @ : chemistry!at!ccl.net Objet : CCL:when to take a logarithm of biological activity in QSAR studies? Dear CCLers, there is an established tradition of taking a LOGARITHM of concentrations (e.g. -log (IC50), -log(ED50) ) as biological activity parameter in QSAR studies. As I understand, this comes either from the need to bring widely different numerical data (like 0.0001 and 0.1) into more balanced scale, or from generally logarithmic nature of biological response to external stimuli. Now, my question is: do you think that when applying other, non-concetration-based types of biological activity, one should also take their logarithm for QSAR studies? I am thinking specifically about percentages, as in "inhibition percentage", which are commonly encountered as results of biological assays. Happy New Year to everybody! Jaroslaw Panek Faculty of Chemistry, University of Wroclaw ul. F. Joliot-Curie 14, 50-383 Wroclaw, Poland -= This is automatically added to each message by the mailing script =- To send e-mail to subscribers of CCL put the string CCL: on your Subject: line and send your message to: CHEMISTRY!at!ccl.net Send your subscription/unsubscription requests to: CHEMISTRY-REQUEST!at!ccl.net HOME Page: http://www.ccl.net | Jobs Page: http://www.ccl.net/jobs If your mail is bouncing from CCL.NET domain send it to the maintainer: Jan Labanowski, jkl!at!ccl.net (read about it on CCL Home Page) -+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+ From sarah.kebbell2~at~mail.dcu.ie Mon Jan 5 09:56:13 2004 Return-Path: Date: Mon, 5 Jan 2004 14:27:05 +0000 Message-ID: <3FCAE98A0002C4BE~at~hawk.dcu.ie> From: sarah.kebbell2~at~mail.dcu.ie Subject: Adventages to use G03 under Unix compared to Windows? To: chemistry~at~ccl.net 1.What are the advanatages of using Gaussian '03 in a Unix based environment as opposed to using it through Windows? 2.Is it possible to submit a calculation in Gaussian '03 to two processors if using a twin cpu with just a single Gaussian license? Thanking you in advance, Sarah Kebbell Sarah Kebbell B.Sc.(Hons) AMRSC, Dermot Brougham Research Group, School of Chemical Sciences, Dublin City University, Dublin 9 Tel: +353 1 700 5731 From chemistry-request@ccl.net Mon Jan 5 10:20:25 2004 Received: from smtp2.ruc.dk (smtp2.ruc.dk [130.225.220.22]) by server.ccl.net (8.12.8/8.12.8) with ESMTP id i05FJsX9003510 for ; Mon, 5 Jan 2004 10:19:54 -0500 Received: by smtp2.ruc.dk (Postfix, from userid 1001) id 5147223886B; Mon, 5 Jan 2004 16:19:53 +0100 (CET) Received: from virgil.ruc.dk (virgil.ruc.dk [130.225.220.110]) by smtp2.ruc.dk (Postfix) with ESMTP id DEA3323830A; Mon, 5 Jan 2004 16:19:50 +0100 (CET) Received: from VIRGIL/SpoolDir by virgil.ruc.dk (Mercury 1.47); 5 Jan 04 16:19:50 +0100 Received: from SpoolDir by VIRGIL (Mercury 1.47); 5 Jan 04 16:19:50 +0100 From: "Jens Spanget-Larsen" Organization: Roskilde Universitetscenter To: "Giju Thomas Kalathingal" , Date: Mon, 5 Jan 2004 16:19:21 +0100 Subject: CCL:Summary: Calculations without Born-Oppenheimer approximation "2nd Call" Reply-To: spanget.-at-.ruc.dk Cc: chemistry.-at-.ccl.net Message-ID: <3FF98E89.26792.14E64BC@localhost> Priority: normal In-reply-to: X-mailer: Pegasus Mail for Windows (v4.01) X-Spam-Checker-Version: SpamAssassin 2.55 (1.174.2.19-2003-05-19-exp) X-Spam-Report: X-Spam-Status: No, hits=-0.5 required=7.0 tests=IN_REP_TO version=2.55 X-Spam-Level: Dear Giju Thomas Kalathingal! Somewhat late, but nevertheless: Michael C. Bvhm and coworkers have for a number of years applied a Feynman path integral Monte Carlo formalism in ab initio calculations of molecular structure and optical transitions. This approach goes beyond the BO approximation; the nuclear positions are evaluated as ensemble averages over large sets of nuclear configurations. See their recent paper and references given therein: Lopez-Ciudad T, Ramirez R, Schulte J, Bvhm MC, J. Chem. Phys. 119(8), 4328-4338, 2003. Yours, Jens >--< =-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-= JENS SPANGET-LARSEN Office: +45 4674 2710 Department of Chemistry Fax: +45 4674 3011 Roskilde University (RUC) Mobile: +45 2320 6246 P.O.Box 260 E-Mail: spanget.-at-.ruc.dk DK-4000 Roskilde, Denmark http://virgil.ruc.dk/~spanget =-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-= From chemistry-request@ccl.net Mon Jan 5 13:17:29 2004 Received: from smtp.goldrush.com (smtp.goldrush.com [206.171.171.11]) by server.ccl.net (8.12.8/8.12.8) with ESMTP id i05IGvX9007108 for ; Mon, 5 Jan 2004 13:16:57 -0500 Received: from goldrush.com (x2-04b-222.goldrush.com [64.162.11.222]) by smtp.goldrush.com (8.12.8/8.12.8) with ESMTP id i05IGrZJ019212 for ; Mon, 5 Jan 2004 10:16:54 -0800 Date: Mon, 5 Jan 2004 10:15:39 -0800 Mime-Version: 1.0 (Apple Message framework v551) Content-Type: text/plain; charset=US-ASCII; format=flowed Subject: CCL: when to take a logarithm of biological activity in QSAR studies? From: Stephen Bowlus To: CHEMISTRY!at!ccl.net Content-Transfer-Encoding: 7bit Message-Id: <2AAF3B58-3FAB-11D8-BED7-000393D4953A!at!goldrush.com> X-Mailer: Apple Mail (2.551) X-MailScanner: Found to be clean X-MailScanner-SpamCheck: X-Spam-Status: No, hits=0.0 required=7.0 tests=USER_AGENT_APPLEMAIL version=2.55 X-Spam-Checker-Version: SpamAssassin 2.55 (1.174.2.19-2003-05-19-exp) It certainly makes sense to express the effective concentration as a logarithm, for the reasons given by several respondents to this query. It must be appreciated, however, that there is an ASSUMPTION here that binding affinity is the activity-limiting feature of a given ligand and especially across a series of ligands, if one is extracting a structure-activity relationship. This assumption is frequently violated if one is using whole-organism data as the endpoint for activity. The distribution characteristics of the logarithm are also statistics-friendly when extracting the model (I assume one is using some sort of regression here). Use of %-inhibition (at a given concentration) is a common practice noted by J Panek, particularly for whole-organism response. Just as use of the log is good in the above case, there are other transformations of this data which give (statistically) better distribution, and these should be investigated when developing an SAR equation. The use of the sqrt(arcsin(X)) comes to mind. Historically, I think use of the logarithm sort of (uncritically) grew out of its use in "Hansch-like" QSAR studies, which share theoretical underpinnings with the classic Hammett relationship (and other free-energy relationships). In medicinal chemistry, the use of -logX arose out of a desire that "bigger numbers are better." sb From chemistry-request@ccl.net Mon Jan 5 13:51:10 2004 Received: from mail.ccmsi.us (mccmsi.jsums.edu [143.132.103.55]) by server.ccl.net (8.12.8/8.12.8) with ESMTP id i05IobX9008094 for ; Mon, 5 Jan 2004 13:50:39 -0500 Received: from FALCON [10.30.6.25] by mail.ccmsi.us with ESMTP (SMTPD32-8.05) id A1D4123800F6; Mon, 05 Jan 2004 12:49:56 -0600 From: "Yevgeniy Podolyan" To: Subject: special issue of the Structural Chemistry Date: Mon, 5 Jan 2004 12:50:27 -0600 MIME-Version: 1.0 Content-Type: multipart/alternative; boundary="----=_NextPart_000_0008_01C3D38A.7E780BD0" X-Mailer: Microsoft Office Outlook, Build 11.0.5510 Thread-Index: AcPTvMjzjK5E9ST2RRapfIfDRCnR8Q== X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2800.1165 Message-Id: <200401051249994.SM02400@FALCON> X-Spam-Status: No, hits=5.1 required=7.0 tests=FORGED_MUA_OUTLOOK,HTML_30_40,HTML_MESSAGE, MISSING_OUTLOOK_NAME version=2.55 X-Spam-Level: ***** X-Spam-Checker-Version: SpamAssassin 2.55 (1.174.2.19-2003-05-19-exp) This is a multi-part message in MIME format. ------=_NextPart_000_0008_01C3D38A.7E780BD0 Content-Type: text/plain; charset="us-ascii" Content-Transfer-Encoding: 7bit Dear Colleagues: I would like to bring to your attention a special (October 2003, Vol. 14, Issue 5) issue of the Structural Chemistry. This issue presents selected papers from the Second Southern School on Computational Chemistry. Please visit the Structural Chemistry homepage (http://www.kluweronline.com/issn/1040-0400/contents) to see the contents and view abstracts of the papers published in this Computational Chemistry issue. Sincerely, Jerzy Leszczynski ------=_NextPart_000_0008_01C3D38A.7E780BD0 Content-Type: text/html; charset="us-ascii" Content-Transfer-Encoding: quoted-printable
Dear Colleagues:

I would like to bring to your attention a = special=20 (October 2003, Vol. 14, Issue 5) = issue of=20 the Structural Chemistry. This issue presents selected papers from=20 the Second Southern School = on=20 Computational Chemistry. Please visit the Structural Chemistry homepage = (http://www.k= luweronline.com/issn/1040-0400/contents)=20 to see the contents and view abstracts of the papers published in this=20 Computational Chemistry issue.

Sincerely,

Jerzy=20 Leszczynski

------=_NextPart_000_0008_01C3D38A.7E780BD0-- From chemistry-request@ccl.net Mon Jan 5 16:26:13 2004 Received: from kafka.net.nih.gov (mailfwd.nih.gov [165.112.130.10]) by server.ccl.net (8.12.8/8.12.8) with ESMTP id i05LPfX9011130 for ; Mon, 5 Jan 2004 16:25:42 -0500 Received: from pollux.cber.nih.gov (pollux.cber.nih.gov [128.231.52.5]) by kafka.net.nih.gov (8.12.10/8.12.9) with ESMTP id i05LPfcD027004; Mon, 5 Jan 2004 16:25:41 -0500 (EST) Date: Mon, 5 Jan 2004 16:14:50 -0500 From: Rick Venable To: Wei Shi cc: chemistry.-at-.ccl.net Subject: Re: CCL:CCL In-Reply-To: Message-ID: References: ReplyTo: Rick_Venable.-at-.nih.gov MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII X-Spam-Status: No, hits=-1.1 required=7.0 tests=EMAIL_ATTRIBUTION,IN_REP_TO,QUOTED_EMAIL_TEXT, RCVD_IN_NJABL,REFERENCES,REPLY_WITH_QUOTES,USER_AGENT_PINE, X_NJABL_OPEN_PROXY version=2.55 X-Spam-Checker-Version: SpamAssassin 2.55 (1.174.2.19-2003-05-19-exp) It should be noted that PDB coords have some empty space within the unit cell, which is assumed to be mostly water. A water content of 30-40% isn't unusual; the water mobility means no electron density is observed for most of it. An implication is that your simulation model is that of a protein in a vacuum, with only a few tightly bound waters. I don't believe this model is equivalent to a protein in solution, and it may not be appropriate to represent it as such. Also, although the sum of kinetic and potential energy is probably constant, it's only loosely an NVE simulation, as the volume is effectively infinite with no boundary conditions. For a solvated protein simulation, I'd monitor the potential energy, the radius of gyration, and the bacbone RMSD relative to the starting structure. When all 3 of these become flat, one could argue that the system is equilibrated; this could require 100s of picoseconds. On Sun, 4 Jan 2004, Wei Shi wrote: > Thanks for your help. Actually, my simulation is started from the PDB, > which includes crystalized water, ion, protein, and ADP. I add missing > residuals, and hydogen atoms. I assign potential type and partial > charge for one of the residuals which does not exist in the rtf file > in the CHARMm. Then, I do some steps of minization. In my system, I > have not added solvent water and not applied the PBC. The total number > of atoms is around 7000. > > I heat my system in 5 ps from 240 K to 300 K, then perform > equilibration for 5 ps. After that, I perform 150 ps of NVE MD > simulation production run. The time step is 0.001 ps. The potential > energy is still drifting down in the production run. For example, I > calculate the average potential in a time slot of 30 ps and the > average is -17506 kcal/mol, the value for the next 30 ps is -17527 > kcal/mol. This energy drift, I suppose, is not significant. The > average difference is 0.1% in 30 ps. > > By the way, I have tried NVT MD simulation. The potential energy is > still drifting down even after 700 ps. > > Generally, how long does it take to get equilibration from your > experience if you start the simulation from the X ray structure? I > have read many papers to hope to see the potential energy versus time > without sucess. Can you give me some reference papers? =+=+=+=+=+=+=+=+=+=+=+=+=+=+=+=+=+=+= Rick Venable 29/500 FDA/CBER/OVRR Biophysics Lab 1401 Rockville Pike HFM-419 Rockville, MD 20852-1448 U.S.A. (301) 496-1905 Rick_Venable.-at-.nih.gov ALT email: rvenable.-at-.speakeasy.org ------------------------------------- "Don't blame me, I voted for Kang." Homer =+=+=+=+=+=+=+=+=+=+=+=+=+=+=+=+=+=+= From chemistry-request@ccl.net Mon Jan 5 15:21:48 2004 Received: from hqmail1.corp.aspentech.com (nathqmail1.aspentech.com [208.201.88.6]) by server.ccl.net (8.12.8/8.12.8) with ESMTP id i05KLGX9010009 for ; Mon, 5 Jan 2004 15:21:16 -0500 Received: by hqmail1.corp.aspentech.com with Internet Mail Service (5.5.2653.19) id ; Mon, 5 Jan 2004 15:20:40 -0500 Message-ID: <63799630D1424545BB6E6B0E98FE2B5604968AD4.-at-.hqmail1.corp.aspentech.com> From: "Mathias, Paul" To: "'Stephen Bowlus'" , CHEMISTRY.-at-.ccl.net Subject: RE: when to take a logarithm of biological activity in QSAR studi es? Date: Mon, 5 Jan 2004 15:20:39 -0500 MIME-Version: 1.0 X-Mailer: Internet Mail Service (5.5.2653.19) Content-Type: text/plain; charset="iso-8859-1" X-Spam-Status: No, hits=-0.5 required=7.0 tests=ORIGINAL_MESSAGE version=2.55 X-Spam-Checker-Version: SpamAssassin 2.55 (1.174.2.19-2003-05-19-exp) There are other reasons why the logarithm is often used in QSAR models: 1. Typically, the quantity being modeled can only be positive. Using the logarithm ensures this. 2. Many QSAR correlations are derived from theory. For example, correlations for activity coefficients are based upon the excess Gibbs Free Energy; the logarithm of the activity coefficient of a particular component in a mixture is related to its partial molar derivative of the mixture excess Gibbs Free Energy. Models for the excess Gibbs Free Energy (e.g., Hildebrand's Regular-Solution Theory and UNIQUAC) invariably result in a mathematical expression for the logarithm of the activity coefficient as a function of composition, temperature and physical quantities representing the intermolecular interaction. It's best to have a model for the target property of interest. If the model is good, an accurate QSAR model will be obtained with only a few adjustable parameters. And, for quantities like activities, the resulting QSAR relationship will usually be in the form of a logarithm. I have a related quote in my files from somebody named D. L. Bunker (I don't know who he is): "Physical Chemistry is research on everything for which the negative logarithm is linear with 1/T." Paul Mathias -----Original Message----- From: Stephen Bowlus [mailto:chezbowlus.-at-.goldrush.com] Sent: Monday, January 05, 2004 1:16 PM To: CHEMISTRY.-at-.ccl.net Subject: CCL:when to take a logarithm of biological activity in QSAR studies? It certainly makes sense to express the effective concentration as a logarithm, for the reasons given by several respondents to this query. It must be appreciated, however, that there is an ASSUMPTION here that binding affinity is the activity-limiting feature of a given ligand and especially across a series of ligands, if one is extracting a structure-activity relationship. This assumption is frequently violated if one is using whole-organism data as the endpoint for activity. The distribution characteristics of the logarithm are also statistics-friendly when extracting the model (I assume one is using some sort of regression here). Use of %-inhibition (at a given concentration) is a common practice noted by J Panek, particularly for whole-organism response. Just as use of the log is good in the above case, there are other transformations of this data which give (statistically) better distribution, and these should be investigated when developing an SAR equation. The use of the sqrt(arcsin(X)) comes to mind. Historically, I think use of the logarithm sort of (uncritically) grew out of its use in "Hansch-like" QSAR studies, which share theoretical underpinnings with the classic Hammett relationship (and other free-energy relationships). In medicinal chemistry, the use of -logX arose out of a desire that "bigger numbers are better." sb -= This is automatically added to each message by the mailing script =- To send e-mail to subscribers of CCL put the string CCL: on your Subject: line and send your message to: CHEMISTRY.-at-.ccl.net Send your subscription/unsubscription requests to: CHEMISTRY-REQUEST.-at-.ccl.net HOME Page: http://www.ccl.net | Jobs Page: http://www.ccl.net/jobs If your mail is bouncing from CCL.NET domain send it to the maintainer: Jan Labanowski, jkl.-at-.ccl.net (read about it on CCL Home Page) -+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+ From chemistry-request@ccl.net Mon Jan 5 16:24:17 2004 Received: from sandmail01.sd.accelrys.com (fw1.sd.accelrys.com [209.120.169.30]) by server.ccl.net (8.12.8/8.12.8) with ESMTP id i05LNjX9011086 for ; Mon, 5 Jan 2004 16:23:45 -0500 To: chemistry.-at-.server.ccl.net Subject: Fw: QSAR - Hansch Award of the QSAR and Modelling Society MIME-Version: 1.0 X-Mailer: Lotus Notes Release 6.0.1CF1 March 04, 2003 Message-ID: From: Osman F Guner Date: Mon, 5 Jan 2004 13:23:40 -0800 X-MIMETrack: Serialize by Router on sandmail01/Server/Accelrys(Release 6.0.2CF1|June 9, 2003) at 01/05/2004 13:23:45, Serialize complete at 01/05/2004 13:23:45 Content-Type: multipart/alternative; boundary="=_alternative 007533A488256E12_=" X-Spam-Status: No, hits=1.3 required=7.0 tests=HTML_20_30,HTML_MESSAGE version=2.55 X-Spam-Level: * X-Spam-Checker-Version: SpamAssassin 2.55 (1.174.2.19-2003-05-19-exp) This is a multipart message in MIME format. --=_alternative 007533A488256E12_= Content-Type: text/plain; charset="ISO-8859-1" Content-Transfer-Encoding: quoted-printable Please see appended, brief description of the Hansch Award of the QSAR and = Modelling Society. If you have suggestions for qualified candidates for=20 the 2004 Hansch Award (young scientists in the field, who are not quite=20 40), please provide the name and a brief description of the candidate's=20 qualifications (CV preferred) to Hugo Kubinyi at (kubinyi.-at-.t-online.de). Osman F. G=FCner, Ph.D. Executive Director Cheminformatics and Rational Drug Design Accelrys Inc., 858-799-5341 osman.-at-.accelrys.com, http://www.accelrys.com ----- Forwarded by Osman F Guner/San Diego/Accelrys on 01/05/2004 01:13 PM = ----- kubinyi.-at-.t-online.de (Hugo Kubinyi)=20 Sent by: qsar=5Fsociety-admin.-at-.accelrys.com 01/03/2004 07:07 AM Please respond to qsar=5Fsociety.-at-.accelrys.com To cc Subject QSAR - Hansch Award of the QSAR and Modelling Society =3D=3D> do not reply, send answers to kubinyi.-at-.t-online.de=20 Dear Members,=20 in 1999, our Society created the Hansch Award , to be given to "young=20 scientists (up to an age of 40), being active in the field of=20 (quantitative) structure-activity modelling".=20 The Hansch Award winners, so far, are=20 Hua Gao, 2000=20 Gabriele Cruciani, 2001=20 Tudor Oprea, 2002=20 David Clark, 2003.=20 Beginning in 2004, a Nomination Committee will select appropriate=20 candidates; afterwards, a Selection Committee will pick the winner, out of = this group. This procedure should avoid any positive or negative bias.=20 Now we are looking for names for 2004. Everybody is invited to come up=20 with proposals (send names to kubinyi.-at-.t-online.de , not to the list).=20 Don't be shy, tell us your favorite candidate or ask a friend to propose=20 your name, and include a short CV and a list of key publications of this=20 person.=20 Best regards and a Happy New Year,=20 Hugo (Chair of the Nomination Committee)=20 Prof. Dr. Hugo Kubinyi, Donnersbergstrasse 9=20 D-67256 Weisenheim am Sand, Germany=20 FAX +49-6353-508233, E-mail kubinyi.-at-.t-online.de=20 HomePage http://home.t-online.de/home/kubinyi=20 --=_alternative 007533A488256E12_= Content-Type: text/html; charset="ISO-8859-1" Content-Transfer-Encoding: quoted-printable
Please see appended, brief descripti= on of the Hansch Award of the QSAR and Modelling Society.  If you have suggestions for qualified candidates for the 2004 Hansch Award (young scien= tists in the field, who are not quite 40), please provide the name and a brief description of the candidate's qualifications (CV preferred) to Hugo Kubinyi at (kubinyi.-at-.t-online.de).

Osman F. G=FCner, Ph.D.
Executive Director
Cheminformatics and Rational Drug Design
Accelrys Inc.,  858-799-5341
osman.-at-.accelrys.com, http://www.accelrys.com
----- Forwarded by O= sman F Guner/San Diego/Accelrys on 01/05/2004 01:13 PM -----
kubinyi.-at-.t-online.de (= Hugo Kubinyi)
Sent by: qsar=5Fsociety-admin@accelr= ys.com

01/03/2004 07:07 AM
Please respond to
qsar=5Fsociety[at]accelrys.com
To
<qsar=5Fsociety@acce= lrys.com>
cc
Subject
QSAR - Hansch Award of = the QSAR and Modelling Society






=3D=3D> do not reply, send answe= rs to kubinyi[at]t-online.de

Dear Members,

in 1999, our Society created the Hansch Award , to be given to "= ;young scientists (up to an age of 40), being active in the field of (quantitative) structure-activity modelling".

The Hansch Award winners, so far, are

Hua Gao, 2000
Gabriele Cruciani, 2001
Tudor Oprea, 2002
David Clark, 2003.

Beginning in 2004, a Nomination Committee will select appropriate candidate= s; afterwards, a Selection Committee will pick the winner, out of this group. This procedure should avoid any positive or negative bias.

Now we are looking for names for 2004. Everybody is invited to come up with proposals (send names to kubinyi[at]t-online.de , not to the list). Don't be shy, tell us your favorite candidate or ask a friend to propose your name, and include a short CV and a list of key publications of this person.

Best regards and a Happy New Year,

Hugo (Chair of the Nomination Committee)


Prof. Dr. Hugo Kubinyi, Donnersbergstrasse 9
D-67256 Weisenheim am Sand, Germany
FAX +49-6353-508233, E-mail kubinyi[at]t-online.de
HomePage http://home.t-online.de/home/kubinyi --=_alternative 007533A488256E12_=--