From owner-chemistry@ccl.net Thu Jun 26 05:24:00 2008 From: "Wai-To Chan chan**curl.gkcl.yorku.ca" To: CCL Subject: CCL:G: Triplet transition states Message-Id: <-37264-080626051835-16586-g1+awv9xGYHVSQVScouMSA-$-server.ccl.net> X-Original-From: "Wai-To Chan" Date: Thu, 26 Jun 2008 05:18:31 -0400 Sent to CCL by: "Wai-To Chan" [chan^curl.gkcl.yorku.ca] <<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<< > Sent to CCL by: "Breton, Gary" [gbreton|,|berry.edu] > Hi everyone, >I hope everyone is enjoying their summer. I have been working on a long term >project (possibly TOO long) in an attempt to locate possible transition >states for the thermal decomposition of a series of small ring heterocyclic >compounds. Upon thermolysis, the compounds liberates nitric oxide (NO) >which is a radical species (which could be important..see below). >I started this project employing the DFT method at the B3LYP/6-311+G(d,p) >level and located a number of transition states. Being a bit nave at the >time, I had set the transition state calculation to search for a saddle >point using the unrestricted B3LYP functional and at a triplet state. I was >able to reproduce these same calculations using MP2/6-31G(d) with few >additional optimization steps. IRC calculations were beautiful and linked >my starting materials to products as expected. The transition states >exhibited expectation values intentionally searched for triplet states). Chemical intuition suggests that the triplet and singlet states of a formal diradical differ only on the spin of one of the two lone electrons each localized at two separate sites. Hence it seems reasonable to expect the geometries of the triplet and the open-shell singlet states to be similar. In such case your triplet calculations should provide a reasonable approximation of the singlet TS geometry. If the electronic structure of your TS arises > from a structural distortion of the closed-shell singlet state of the reactant from its equilibrium geometry to form a partial diradical which exhibits only a moderate RHF--->UHF (or RDFT--->UDFT) instability you triplet state structure may not provide a good starting geometry for the search of the diradical TS. It is even possible such a TS has to be modelled as a closed-shell singlet state using the RHF-based methods. This is indeed the case for the characterization of the TS structures associated with the concerted mechanisms of organic cycloadditional reactions in general. I presume you have ruled out the applicability of RDFT to the singlet state of the TS. Here is how I would proceed with the search for a diradical TS. Starting with the triplet TS structure I will check the wavefunction stability of the RHF wavefunction of the closed-shell singlet state of the geometry using the option STABLE=OPT. This could be time-consuming depending on the size of your system. You may instead use the option GUESS=MIX along with UHF to obtain a broken-symmetry solution. The guess=mix option is not always reliable and for such case the procedure suggested in the post of professor Clark would be useful. But to be pragmatic just use the stability code in GAUSSIAN like a black-box tool for a quick answer Assuming the stability run indicates an instability and then generates an UDFT solution for the singlet you could save the wavefunction for your TS search. You may proceed to start the TS search from this geometry using UB3LYP along with guess=check to read in the wavefunction. I suggest you to use 6-31+G(d) or 6-31+G(d,p) for a preliminary search of the TS. You can always improve the level of theory to a larger basis set using the geometries and wavefunction obtained with 6-31+G* which should save cpu time considerably for the hessian calculational step in the TS search. During the course of the TS search monitor the evolution of the SCF solution closely. If the UDFT solution converts back to a RDFT which you seem to have encountered then you are in trouble. One possible cause of such UDFT--->RDFT SCF convergenc failure could be the substantial geometric changes between optimization steps. In such case you may try a smaller step size. Diradical PES also tend to be rather floppy. If affordable using the horribly costly CALCALL option instead of CALCFC may be desirable. If all attempts to locate a diradical TS fail you should then consider the possibility of the absence of the TS in the PES. It is quite possible that the presence of a diradical TS is the function of the amount of HF exchange in the DFT. Take a look at the size of in the UDFT solution obtained from RDFT stability calculation at the geometry of the triplet TS. A moderate value of close to zero may indicate that the triplet TS geometry is in the vicinity of the onset of the "triplet-instability" of the underlying RDFT solution. Give a try to BHandHLYP which has a larger mix of HF exchange in it for the stability calculation. You very likely would obtain a larger . In such case geometry optimization with BHandHLYP is less prone to convergence back to a RDFT solution and you stand a better chance of locating the diradical TS. Wai-To Chan >Later on, after reviewing a number of papers, I began to realize what I >needed to do was search for the same TS using unrestricted (open-shell) >procedures but optimizing to a singlet state. Under these conditions, I >cannot locate ANY of the transitions states even though I have tried >manipulating the starting geometries of the input TS structures as well as >through use of the QST2 search feature in Gaussian. I have employed the >Guess= Mix option in these calculations as well. The calculations fail >after the molecule essentially blows apart or relaxes to something related >to the starting material with a residual imaginary frequency. >While I am beginning to come around to the fact that CASSCF calculations or >something similar may be needed here (which I admit to being unqualified to >carry out), is there something salvageable from all these calculations? Is >there a situation where a triplet optimized TS means something? Or is there >some "trick" to getting these TS structures (or similar) to find to a >saddle >point as singlet structures? >I hope I've provided enough information for some answers. Thanks for any >suggestions. >Best regards, >Gary W. Breton From owner-chemistry@ccl.net Thu Jun 26 05:57:01 2008 From: "Alberto Sergio Garay sgaray]^[fbcb.unl.edu.ar" To: CCL Subject: CCL: Problem compiling tinker binaries....(Solved) Message-Id: <-37265-080625195114-18494-vUdw6sPzBMXnB/hh0rJP5Q^^^server.ccl.net> X-Original-From: Alberto Sergio Garay Content-Disposition: inline Content-Transfer-Encoding: quoted-printable Content-Type: text/plain; charset=ISO-8859-1; DelSp="Yes"; format="flowed" Date: Wed, 25 Jun 2008 20:50:43 -0300 MIME-Version: 1.0 Sent to CCL by: Alberto Sergio Garay [sgaray{=}fbcb.unl.edu.ar] Thank you, Don I have found the problem in the file that you have cited. I have =20 downloaded this file again and after that I was able to compile it =20 without any problems. Thank you again. Sergio Garay Don Steiger sd00_2002]|[yahoo.com wrote: > I checked my copy of Tinker, and rsolv, asolv are defined in =20 > "solute.i". "solute.i" is included in both "analyze.f" and =20 > "born.f". > > --- On Wed, 6/25/08, Alberto Sergio Garay sgaray .. fbcb.unl.edu.ar =20 > wrote: > > From: Alberto Sergio Garay sgaray .. fbcb.unl.edu.ar =20 > > Subject: CCL: Problem compiling tinker binaries.... > To: "Steiger, Don " > Date: Wednesday, June 25, 2008, 3:10 AM > > Sent to CCL by: Alberto Sergio Garay [sgaray : fbcb.unl.edu.ar] > Hi > Don > > That's the problem. There is not any defined variable with these =20 > names (rsolv, asolv) in any ".i" files. > > I have downloaded the source tinker's files many times to check > their number and sizes and I have not found any problem =20 > with this yet. > > --=20 Dr. Sergio Garay Facultad de Bioquimica y Cs. Biol=F3gicas Universidad Nacional del Litoral Santa Fe - Argentina C.C. 242 - Ciudad Universitaria - C.P. S3000ZAA Argentina Ph. +54 (342) 4575-213 Fax. +54 (342) 4575-221 --=20 Dr. Sergio Garay Facultad de Bioquimica y Cs. Biol=F3gicas Universidad Nacional del Litoral Santa Fe - Argentina C.C. 242 - Ciudad Universitaria - C.P. S3000ZAA Argentina Ph. +54 (342) 4575-213 Fax. +54 (342) 4575-221 From owner-chemistry@ccl.net Thu Jun 26 08:55:00 2008 From: "Barry Hardy barry.hardy!^!vtxmail.ch" To: CCL Subject: CCL: Drug Discovery Informatics, eCheminfo Autumn Meeting Message-Id: <-37266-080626082719-1319-PdULFzC6YswvX2dF6WYsXw-,-server.ccl.net> X-Original-From: Barry Hardy Content-Transfer-Encoding: 7bit Content-Type: text/plain; charset=ISO-8859-1; format=flowed Date: Thu, 26 Jun 2008 13:26:59 +0200 MIME-Version: 1.0 Sent to CCL by: Barry Hardy [barry.hardy!A!vtxmail.ch] Latest Advances in Drug Discovery Informatics eCheminfo Autumn Community of Practice Meeting 14-17 October 2008 Bryn Mawr College, Bryn Mawr, Philadelphia, USA Conference Link: Website: http://echeminfo.com/COMTY_conferences Blog: http://barryhardy.blogs.com/cheminfostream/ Program (pdf): http://barryhardy.blogs.com/cheminfostream/files/eChemProgramBrynMawr08-Final-v2.pdf Themes: Cheminformatics, Bioinformatics, Medicinal Chemistry, Drug Discovery Innovation, Structure-based Drug Design, Screening, Docking, Structural Biology, Predictive Toxicology, Predictive ADME, Chemogenomics Program Summary Docking & Scoring, chaired by Chaya Duraiswami (GlaxoSmithKline) Application of MM-PBSA Free Energy Methods in Drug Discovery, chaired by Judith Lalonde (Bryn Mawr College) Accurate Calculation of pKas, chaired by Paul Labute (Chemical Computing Group) In Silico-based Chemogenomics, chaired by Fabrice Moriaud (MEDIT) PDB Ligands: Analysing their Structure & Binding Data, chaired by Marc Nicklaus (National Institutes of Health) Predictive ADME, chaired by Anthony E. Klon (Pharmacopeia Drug Discovery) Predictive Toxicology, chaired by Artem Cherkasov (University of British Columbia) Pre-Conference Workshop, 13 October Best Practices Virtual Screening Workshop chaired by Barry Hardy (Douglas Connect) Speakers John Irwin (UCSF), Georgia McGaughey (Merck), Johannes H. Voigt (Schering Plough), Lance Westerhoff (Quantum Bio), Zsolt Zsoldos (SimBioSys), Alexey Ornufriev (Virginia Tech), David Case (Rutgers University), Rommie Amaro (USCD), Peter Coveney (Univ. College London), Anna Kohlmann (Ariad Pharmaceuticals), Scott Brown (Abbott), Emil Alexov (Clemson University), Jens Erik Nielsen (University College Dublin, Ireland), Matthew Davies (Jenner Institute, UK), Maja Mihajlovic (City College of New York), Michael Keiser (UCSF), Brian Marsden (University of Oxford, UK), Alex Tropsha (UNC), John Westbrook (Rutgers), Howard J Feldman (CCG), Igor V. Filippov (NCI), Raul Cachau (ATP, SAIC-Frederick), Vincent T. Moy (University of Miami), Paul Hawkins (OpenEye), Yulia Borodina (NCBI), Gerhard Wolber (Inte:Ligand, Austria), Marc Nicklaus (NCI), James P. Snyder (Emory), Anne Chaka (NIST), Esther Kellenberger (Univ. Strasbourg, France), Renxiao Wang (SIOC, Shanghai, PR China), Jim Dunbar (University of Michigan), Janna Wehrle (NIGMS), Anton Hopfinger (University of New Mexico), Heidi Einolf (Novartis), Yojiro Sakiyama (Pfizer), Olga Obrezanova (BioFocus DPI, UK), Anthony E. Klon (Pharmacopeia), Artem Cherkasov (University of British Columbia, Canada), Ann Richards (US EPA), Curt Breneman (RPI), Barry Hardy (Douglas Connect), Weida Tong (FDA) CFP We invite contributed talks from members of academic, government research and commercial organizations on areas of new research and innovation involving drug discovery research informatics. The work presented should involve innovative new method development or application to drug discovery problems and involving methods from computational chemistry, computational biology, cheminformatics or bioinformatics. Studies including experimental work in medicinal chemistry, screening, experimental toxicology, pre-clinical evaluation, lead optimisation and translational medicine are welcome. Abstracts (300-500 words) should be submitted to echeminfo -[at]- douglasconnect.com by 31 July 2008, and be accompanied by a short biography of the presenting author (300-500 words). Abstracts approved by the scientific organizing committee will be selected for scheduling on the conference program and in meeting poster sessions. Authors will be notified of acceptance as soon as a review of submitted materials takes place and at the latest by 15 August 2008. Bursary Award Bursary Awards will be used to support the attendance of a selection of academic young investigators at the meeting and workshops. Applicants can be working in any area of research related to drug discovery at the postdoctoral, graduate student and senior undergraduate levels. To apply for the bursary please send an email with a) your abstract and biography (300-500 words each), b) your CV of 1-2 pages, c) a short description of your interests and career motivations related to drug discovery (300-500 words) to echeminfo -[at]- douglasconnect.com by 31 July 2008. The recipients of the bursary awards will be selected based on an evaluation of the quality and innovation of the described research and the potential positive impact of attendance at the meeting on their research and career progress. Authors will be notified of acceptance by 15 August 2008. Poster Session All InterAction Meeting registrants are eligible to present a Conference Poster. The Poster Sessions will take place in the evenings in Thomas Great Hall on campus, where refreshments and dinner are also served. Poster Abstracts (300-500 words) with Title, Institution, Authors and Contact Information should be submitted to barry.hardy -[at]- douglasconnect.com Abstracts will be considered based on date of submission and quality, and will be reviewed and accepted as they are received. To be considered for the formal program, they should be submitted at the very latest by 31 August 2008. We gratefully acknowledge the sponsorship support of: Chemical Computing Group Merck Research Laboratories SimBioSys Contact: Program: Dr. Barry Hardy, eCheminfo Community of Practice, Douglas Connect. Tel: +41 61 851 0170. barry.hardy -[at]- douglasconnect.com Registration Enquiries: Nicki Douglas, Douglas Connect, Baermeggenweg 14, 4314 Zeiningen, Switzerland. Tel: +41 61 851 0461. echeminfo -[at]- douglasconnect.com or go to: http://echeminfoBM810.eventsbot.com From owner-chemistry@ccl.net Thu Jun 26 09:30:00 2008 From: "Hazai Eszter eszter.hazai(_)virtuadrug.com" To: CCL Subject: CCL: Docking Server announcement Message-Id: <-37267-080626091504-14846-oFUubBI8b8HYIDholY4Ciw]=[server.ccl.net> X-Original-From: "Hazai Eszter" Content-Transfer-Encoding: 7bit Content-Type: text/plain; charset="us-ascii" Date: Thu, 26 Jun 2008 14:12:23 +0200 MIME-Version: 1.0 Sent to CCL by: "Hazai Eszter" [eszter.hazai-x-virtuadrug.com] Stewart Computational Chemistry and VirtuaDrug Ltd are pleased to announce the launch of Docking Server, a new web accessible service for carrying out high quality molecular docking calculations. The service is accessible at http://www.dockingserver.com. Free access is provided for academic users without registration using a common workspace. Upon free registration the users can get a private workspace as well. Data storage of the input and output files, high-priority jobs, e-mail and forum support are available upon payment. Docking Server offers a web-based, easy to use interface that handles all aspects of molecular docking from ligand and protein set-up through results representation integrating a number of software methods frequently used in computational chemistry. It integrates the MOPAC2007 program (Stewart, 2007) for accurate pH-dependent protonation and ligand partial charge calculation in order to increase accuracy of docking calculations. The AutoGrid / AutoDock 4.0 (Morris, et al., 1998) program package is used for docking calculations. While the user friendly interface of Docking Server enables docking calculations and evaluation of results to be carried out by researchers from all fields of biochemistry, Docking Server also provides full control on the setting of specific parameters of ligand and protein set up and docking calculations for more advanced users. The application can be used for docking and analysis of single ligands as well as for high throughput docking of ligand libraries to target proteins. www.dockingserver.com is due to commence full operation at the end of June, 2008. For further information on Docking Server or for a free 3-day trial that provides access to a fully functional service, giving you complete access to all features of Docking Server, please do not hesitate to contact us at info_._virtuadrug.com. David Gallagher for Stewart Computational Chemistry dgallagher_._cacheresearch.com Eszter Hazai Virtua Drug eszter.hazai_._virtuadrug.com From owner-chemistry@ccl.net Thu Jun 26 13:36:00 2008 From: "weill naweill(a)gmail.com" To: CCL Subject: CCL: MACCS Message-Id: <-37268-080626125500-13603-6cwTnnXz5SpwvuxTkRdOXA*server.ccl.net> X-Original-From: "weill" Content-Transfer-Encoding: 7bit Content-Type: text/plain; charset="us-ascii" Date: Thu, 26 Jun 2008 17:53:20 +0200 MIME-Version: 1.0 Sent to CCL by: "weill" [naweill(a)gmail.com] Dear CCLusers, I am currently PhD student. I am looking for a free (at least for academics) implementation of MACCS keys. The only one I found is implemented in MOE but unfortunately, MOE modify structures of compounds during the loading procedure. Thank you Best Regards Nathanael Weill