[ Home ] [ About/Contacts ] [ Meetings ] [ Members ] [ News ] [ Positions ] [ Resources ] ------------------------------------------------------------------------------------------------------------------------------------------------ Editorial Memberships Dues Election of New Members of the Board World Wide web Activities of Local Discussion Groups QSAR Discussion Group on the Internet Reports on Recent Meetings Contributions of Society Members Im Memoriam The Journal Quantitative Structure-Activity Relationships Meetings and Courses Books Software Miscellanous _________________________________________ Editorial The Quiet Society The QSAR and Modelling Society seems to be a unique organization, in several respects. In its program and self-understanding, the main goal is to improve the contact between scientists being active in the field of quantitative structure-activity relationships, molecular modelling and computer-aided design. While it is relatively easy to spread the necessary information, e.g. by updating the membership directory and sending it to all members, we have no indication that our members do use this information. Han van de Waterbeemd has installed, with the help of Dr. Didier Rognan and Prof. Gerd Folkers, a WWW page for our Society, which includes much valuable information but, unfortunately enough, nearly no information provided by individual members. While Han and me, as well as some of the Board members can collect information on meetings, upcoming QSAR journal issues and other technical information, we heavily depend on contributions of our members on new approaches, programs, tips and tricks, informations on relevant new (hitherto unpublished) results, etc. Another indication of low interest in the activities of the Society was the fact that only 59 members (out of about 400, at that time) participated in the vote of the new board members. An even much lower number of members answered the question raised by Han van de Waterbeemd, whether they will not need a printed version of the Newsletter in the future (maybe, they have no access to the Internet) and whether they agree or disagree to have the names and addresses of our members published in the Internet. A first step to improve the contact between the members was done by our Russian colleagues. Last month they founded a Russian section of The QSAR and Modelling Society (see report by Prof. Oleg Raevsky), an activity which is highly appreciated by the Board. Such local groups will be able to organize meetings on a more regular basis than the biannual QSAR Symposia and we are looking forward to hearing more about their activities also in the future. We would like to encourage other local communities to follow the example of the Russian group. In addition, we would like to ask for your part to change the situation that our society is still a Quiet Society. There is another fact which bothers me since long. Besides the QSAR community in the field of drug design and agricultural products, there grew another QSAR community in toxicology and environmental sciences. Both develop more or less independently and have separate meetings. Last week I had the chance to attend the 7th International Workshop on QSARs in Environmental Sciences, in Helsingor, Denmark (see report by M.T. Cronin). From my point of view, this was a very interesting and successful meeting. I am absolutely sure that both communities would benefit from at least some joint activities, e.g. common symposia, possibly with parallel sessions. Some of you may have realized that we announced our Society in some scientific journals. Many new members have joined the Society in the meantime. If you have any proposals or suggestions for additional activities of our Society or if you have contributions to our Newsletter, please send them to us. We would like to come to at least three or four issues per year but we need your active assistance to achieve this. Hopefully, next time I will be able to report on a "Lively Society". Hugo Kubinyi July 1996 _________________________________________ Information of the Secretary The number of members increased between November 1995 and October 1996 from 375 to 500. However, only ca 220 paid their 1996 fees (see next page what you can do about it!) Han van de Waterbeemd October 1996   _________________________________________ Membership dues We would appreciate if you could send every year, in its first quarter, a 10$-cheque, payable to a US bank, in US-$, to our treasurer, James King P.O. Box 116 Balsam, NC 28707-0116 USA We understand that for some of you this may be difficult. As possible alternatives we propose a) to pay 30 US-$, for three years. This reduces the relative amount of expenses. b) to send a 10 US-$ note by normal mail to James King or in Europe to Han van de Waterbeemd - at your personal risk. c) to select a person in your country who cashes the membership fees for all of you and sends the total amount to James King. Toshio Fujita does this already for Japan. Other modes of payment are so expensive that the larger amount of your fee might be wasted for the bank and exchange charges.   _________________________________________ Election of new members of the board January 31, 1996 was the deadline for the election of three new board members, from nine candidates. We received 59 votes, one of them being an anonymous vote (this one not counted). The names of the new Board Members are (in alphabetical order): Sergio Clementi, Italy Peter Goodford, UK Bernard Testa, Switzerland. Congratulations and welcome in the Board! To give the members at least some information: Two of these persons were clearly in front, receiving a clear majority of the votes. The other person received one vote more than two (!) of the remaining candidates. Thus, the race was very close. Many thanks to all other candidates for having participated in this democratic act! Hugo Kubinyi March 1996   _________________________________________ www The latest news on the Society can always be found in our Home Page. Consult these pages regularly and send us your comments and info to add. Tip of the month: J. H. Krieger, New software kicks in, Chem. & Eng. News (September 18, 1966), pp. 30 - 37, which is a report from the recent ACS meeting. The article is also available on the WWW at http://pubs.acs.org. Click on "What's New or "Hot Articles" Reference data sets:A new topic in the Societies Home Page is Data Reference Sets. Here we plan to make available typical data sets frequently used to test new approaches, e,g., the Selwood data. Such data sets should be send to Dr. Didier Rognan at the ETHZ (email: didier@pharma.ethz.ch) in ASCII format and include reference(s) to the original paper(s). Alternatively you may send a pointer to such data within your own Home Page.   _________________________________________ Activities of local discussion groups The Spring 1996 meeting was held on April 2nd at the University of Portsmouth and the Autumn 1996 meeting hosted by Unilever Research at Prot Sunlight on October 16th. Each of these meetings consisted of a series of oral contributions, as well as software demonstrations. Iain McLay at Rhône-Poulenc Rorer is preparing the Spring 1997 meeting and is looking for speakers (iain.mclay@rp.fr). More information about the UK group can be obtained from John Bradshaw (jb2314@ggr.co.uk). Han van de Waterbeemd, October 1996 The Organizing Meeting of Russian Section of the QSAR and Modelling Society has been held in the Institute of Biomedical Chemistry (IBMC) of Russian Academy of Medical Sciences (Moscow) on June 3, 1996. IBMC is the leading organization which coordinates the researches on Computer Aided Drug Design in Russian State Research Program "Research and Development of New Drugs by the Methods of Chemical and Biological Synthesis". Jointly with the Institute of Physiologically Active Compounds of Russian Academy of Sciences (Prof. Oleg Raevsky group) and Chemical Department of Moscow State University (Academician Nikolai Zefirov group) IBMC (Prof. Vladimir Poroikov and Prof.Alexis Ivanov groups) pioneered the organization of Russian Section of the QSAR and Modelling Society. More than 40 scientists from Moscow, Ivanovo, Ufa, and Almaty academic and industrial Institutes have participated in the Organizing Meeting. They have represented different specialists: medicinal chemistry, pharmacology, toxicology, informatics & computer science, etc. Several scientists from Sant-Peterburg, Pyatigorsk, Chelyabinsk, Barnaul, Novokuznetsk have informed that they would like to be a member of Russian Section of the QSAR and Modelling Society, however they can not come to the OrganizingMeeting. The Board of Russian Section of the QSAR and Modelling Society have been elected: UK QSAR Discussion Group Formation of the Russian branch of the Society Alexander Archakov, Academician, Sc.D., M.D., IBMC Yuliya Borodina, IBMC - Secretary Vladimir Poroikov, Professor, Sc.D., IBMC - Vice Chair Oleg Raevsky, Professor, Sc.D., IPAC - Chair Nikolai Zefirov, Academician, Sc.D., MSU It has been decided that the main purpose of Russian Section of the QSAR and Modelling Society is the promotion of collaboration between Russian and foreign scientists in the fields of QSAR, SAR, Molecular Modelling, and Computer Aided Drug Discovery. Therefore, the Russian Section intends to provide its activity in close collaboration with the International Board of the QSAR and Modelling Society. In 1996-1997 Russian Section suggests to provide the following actions: 1.Exchange of information with the International QSAR and Modelling Society on regular basis. 2. Informing the Russian members on worldwide activity in the fields of QSAR, SAR, Molecular Modelling, and Computer Aided Drug Discovery (meetings, books, journals, Internet news, etc.). 3. Regular lectures provided by Russian and foreign leading researchers in these fields. 4. Organization of the 1st Russian Conference on Computer Assisted Molecular Design with the participation of some foreign scientists (Chernogolovka, Moscow Region, January-February, 1997). 5. Organization of Special Section on QSAR, SAR, Molecular Modelling, and Computer Aided Drug Discovery in the Journal "Problems of Biomedical Chemistry (Moscow)" published by IBMC. 6. Preliminary work to prepare the Program on development of Computer Aided Molecular Design in Russia. Any suggestions and proposals for the directions of Russian Section of the QSAR and Modelling Society activity are appreciated and considered. Do not hesitate to contact us for further information. Prof.Dr.O.Raevsky, Chair; Prof.Dr.V.Poroikov, Vice Chair Vladimir V. Poroikov, Ph.D.(Biophys.), Sc.D. (Pharmacol.) Russian Section of the QSAR and Modelling Society Head of Lab. Structure-Function Based Drug Design Institute of Biomedical Chemistry RAMS Institute of Biomedical Chemistry RAMS Pogodinskaya Str., 10 , Moscow, 119832, Pogodinskaya 10, Moscow 119832, Russia Russia Tel: +7 095 246-3380, Fax: +7 095 245-0857, E-mail: qsarm-rs@ibmh.msk.su Phone:+007 (095)246-3380, Fax:+007 (095)245-0857, E-mail: vvp@ibmh.msk.su A free copy of 3D-QSAR (Ed. H. Kubinyi) was sent as a gift of the Society to the Russian group.

The 7th International Workshop on QSARs in Environmental Sciences was held at Elsinore, Denmark from 24-28 June 1996. It was hosted by the National Environmental Research Institute of Denmark and was extremely well organised by Dr Fei Chen and her colleagues. This was a pleasant and informal meeting, with an cordial social atmosphere, not least because the Workshop was organised in the same week as the conclusion of the European Football Championships being held in England. Unfortunately the number of delegates was slightly down on the previous Workshop. It was especially regrettable that several scientists from China and Russia who had submitted abstracts were unable to attend and contribute.

Traditionally this workshop concentrates on the use of QSAR to predict toxicity and other properties of environmental relevance. As such it seems to be increasingly polarised from pharmaceutical QSAR meetings (such as the 11th European Symposium on QSAR held in September 1996). Unfortunately very few people cross over from one meeting to another which denies them the opportunity of being exposed to other methods. Good examples of why we should take notice of the ‘other QSAR community’ were illustrated by an excellent presentation by Dr Hugo Kubinyi who demonstrated the importance of receptor binding for biological and toxicological activities. Indeed, our colleagues from the pharmaceutical QSAR community should take note also of the advances in toxicological QSAR and integrate them into their own studies, for instance the prediction of drug toxicity, human health effects, or the environmental impact of their manufacturing processes.

The meeting was dominated by work on environmental toxicity. This is currently a truly exciting and challenging area. Much work was reported on the use and identification of mechanisms of toxic action to develop QSARs for toxicity prediction. In addition efforts to model ‘reactivity’ are clearly well advanced with molecular orbital calculations such as LUMO and superdelocalisability being commonly expressed. Other areas of interest included the prediction of biodegradation. It was a shame, however, that very little work was presented on the prediction of human health effects, an area which should be encouraged for future meetings.

Methods to predict physico-chemical properties are also well developed, inevitably log P is the best developed and described but other prediction methods reported included models for Henry’s Law Constant, vapour pressure, soil sorption coefficient.

The meeting also saw the presentation of the 1st QSAR Award. In a meeting dominated by considerations of mechanisms of action it was fitting that the award went to Dr Hans Konemann in recognition of his pioneering work to develop QSARs for non-polar narcosis to the guppy. His publications are cited widely, and are should be considered to be the foundation for modern environmental QSAR.

Mark T. Cronin, August 1996

The Chemometrics IV Conference was held in Brno, Czech Republic from the 8th to the 12th September 1996. Brno is a city of some half a million people about 200 km east of Prague, in Moravia and close to the border with Slovakia. About 60 people attended the conference, most of whom were from the Czech Republic, but with a good number from other European countries. Notable delegates from afar were Toshio Fujita from Japan and Russell Drago from the USA. There was a total of 16 invited lectures, 7 other oral presentations and 43 posters. Chemometrics covers, of course, a wide range of disciplines, and quite a number of presentations at the Conference were concerned with analytical chemistry and spectroscopy. However, 8 of the lectures and 8 posters dealt specifically with QSAR, whilst a number of others were concerned with LFER. It was a great pleasure for me to hear Toshio Fujita talk on a number of commercial success stories of drugs and pesticides that had been devised using QSAR, and to listen to Otto Exner telling us about the incorrect use of statistics. The most exciting presentation, for me, was that of Paul Geladi, who spoke on the relationship between data and sound, and how scientific information could be encoded in sound. For example, he played music that encoded DNA sequences. It occurred to me that this might be a way of comparing the similarity of molecules. An excellent social programme was incorporated into the conference - we learned a lot of Moravian history and heard a lot of Moravian folk music, as well as drinking plenty of Moravian wine.

John Dearden, September 1996

	QSAR96
	Chemometrics IV :Conference in Brno, Czech Republic

This biannual event was held at the beautiful campus of the University of Lausanne and was attended by 325 participants. In a full lecture programme from Sunday evening upto Friday at noon the full spectrum of current activities was covered. Lectures were divided into five sections: Chemometrics (plenary lectures by Hugo Kubinyi and Peter Jurs), Lead Finding Strategies (Richard Lewis, Hans-Joachim-Böhm), Computational Approaches in Drug Disposition (Dennis Smith and Aldo Begnini), 3d-QSAR and Molecular Modelling (Gariele Cruciani and Thomas Lengauer), Future Challenges (Gerry Maggiora amd Christine Humblet). In three poster sessions ca 150 posters were displayed and sprightly discussed. Interactions among the participants were further optimized by a number of social events, starting with a visit to the Olympic museum, and furthermore an organ concert in the cathedral, boat trip and buffet on the lake and finally a gala dinner including a dance party. It is the intention of the organizers to bring out the Proceedings by the end of 1996. The next chairman to organize the 12th symposium in the European series is Klaus Gundertofte, who works at H. Lundbeck at Copenhagen. Denmark we look forward to 1998! See below for details.

Han van de Waterbeemd, symposium chairman, September 1996

!!!! A number of abstracts books are still available from undersigned.

11th European Symposium on QSAR: Computer-Assited Lead Finding and Optimization in Lausanne, Switzerland.

A work settles nothing, just as the labour of a whole generation settles nothing. Sons and the morrow, always start afresh.

Ever since the early days of Ehrlich and his “magic bullets” there has been the implicit assumption that there is some relationship between the structure of a compound and its observed biological activity. As the 20th Century progressed this relationship was extended to include the physical properties of the compound. There was a realisation that biological activity resided in specific features of the molecule, and that indeed most chemical compounds were devoid of useful biological activity. This meant that random testing on the Micawber Principle, that “something would turn up”, was not a sensible way to run a pharmaceutical business. This view is supported by the fact that major selling drugs since the 1970’s arose from testing appropriate compounds (1,2).

In effective drug discovery there is a balance between the number of targets that can be investigated, the number of compounds available for test and the capacity of the screening/testing effort.

QSAR in the pharmaceutical industry -- The sleeper awakes.

Whenever this balance is seriously disturbed a pharmaceutical company’s discovery effort is compromised. Historically there have always been more compounds than screens could cope with, and so it was necessary to make a choice of the type of compound that was screened. The targets were chosen on pragmatic bases. We were after all, in the business of treating diseases which were not treated at all, or were treated badly. It was pointless chasing a more sophisticated approach to a disease which was already treated well, unless there were a real advantage, no matter how intellectually stimulating the pursuit may be.

The way compounds numbers were reduced was first by making use of the information about the target. Compounds were chosen to “ask the receptor questions”, so it is self-evident that you do not test steroids against adenosine receptors, you test adenosine analogues first, or 5,6 nitrogen containing bicycles. Sometimes this, coupled with difficult chemistry was sufficient to keep the compound supply in balance.

When this was not sufficient it was necessary to pick a subset of the accessible, appropriate compounds. This is where the multivariate tools of QSAR came in. Two major approaches are illustrated by the work of Goodford et al, (3) and Woolridge (4). In Goodford’s approach a set of key intermediates was chosen from commercially available compounds. Woolridge chose a set of substituents which would span an appropriate chemical space. It was up to the researcher to prepare those. Either of these routes ensured that the data was appropriate for statistical analysis, and in appropriate cases the optimisation of drug activity. Multivariate design approaches encouraged more than one thing to be changed at once.

As knowledge about the macromolecule increased there was a view that the exact compound could be designed to fit the active site. Physical properties were forgotten as were key principles of chemistry such as entropy in the pursuit of Nintendo chemistry. There would now be no need to screen compounds other than in silico. History will show whether this phase was more than just a prolific consumer of the profits of more effective approaches to drug discovery. In more recent years, technology allowed the capacity of screens to be increased enormously, and for a short period it was not the rate limiting step. There was talk of collecting 1 billion data points a year. However economics come into this, if it costs a dime for every data point, then $100M is a lot to spend on what is, after all, a small proportion of a pharmaceutical company’s activities. Real costs are probably nearer $1.00 per data point.

Other practical questions arise, if these data are real numbers you would need 16 Gbytes just to store them!! The number of targets rapidly increased as information from the genome project became generally available. The choice of which targets to screen is now a matter of grave concern. Even the major players cannot keep all possible screens running all of the time. Some companies now choose representative subsets of targets. The classical rôles of target and compound seemingly being reversed. However this testing of targets against a fixed set of compounds is what pharmacologists have been doing since the early years of this century. As early as 1982, Lewi (5), amongst others, promoted the idea that QSAR techniques could reduce the number of screens it was necessary to run. Automated chemistry, and the opening up of the former USSR made many millions of compounds available for screening. So in true circular fashion, we are now back to needing to chose compounds which are

(a) Appropriate for the target

(b) Are representative of the available/accessible appropriate compounds.

i.e. the very things that QSAR practitioners have skills in. True the size of the data sets have increased significantly and it masquerades under the title of Diversity Analysis in many glossy journals, but the science is still the same. Automated chemistry and screening offer a real challenge for the QSAR practitioner to use their skills in

	Choosing appropriate well designed compound sets.
	Analysing the large amount of data which is produced by automated screens.
	Feeding back results into the target selection process combined with the macromolecular information from bioinformatics and protein modelling.

In 1984 Stefan Unger (6) wrote an article “Whither QSAR, wither QSAR”. Quite clearly it is alive and well and living as Diversity Analysis!!

(1) Ganellin, C.R., Chron. Drug Discovery (1982) Volume 1, 1-38

(2) Bradshaw, J. , Chron. Drug Discovery (1993) Volume 3, 45-81

(3) Wootton, R., et al , J. Med. Chem. (1975) 18 , 607

(4) Woolridge, K. J. Eur. Med. Chem.

(5) Lewi, P.J., Multivariate Data Analysis in Industrial Practice (1982) John Wiley

(6) Unger, S., QSAR in the Design of Bioactive Compounds (1984) J.R.Prous

John Bradshaw, September 1996

Developments in pharmaceutical research continue to present challenges for the QSAR community. Currently, molecular diversity and combinatorial chemistry provide an interesting and important arena for development and application of approaches to molecular representation. Combinatorial libraries and automation of biological assays are producing large libraries of diverse chemical structures with associated biological property values, which require analysis.

To make effective use of these large structure and property knowledge bases, various analyses are necessary to compare molecules within a database as well as to characterize and compare databases. Analysis calls for ability both to determine molecular similarity among structures as well as reveal relationship to biological activities and chemical properties. Further, because of the very large number of structures involved, speed is also a critical factor.

A wide range of molecular descriptors has been provided by the Molconn software which is currently released in a new version, Molconn-Z (1). The structure indices from Molconn are being used in many laboratories for representation in chemical databases (2,3). Recently, topological indices have been compared to those based on 3-D representations with some surprise expressed over the good performance of the topologically based representations (3-6).

A basic premise of the molecular topology approach is that representation of molecular structure includes more than geometry and energy. Effective representation of molecular structure includes a range of structure information which is implicit in the geometry-energy manifold of the molecule, from primitive counts of atoms and substructures to weighted combinations of electronic and topological features. In a very basic way, the topology (connectivity within the molecular skeleton) determines the range of geometry-energy available to the molecule. The connectivity and atom identities within the skeleton provide the basis for representation of the whole molecule. In this sense it is not strictly accurate to refer to topological descriptors as 2D. The indices are nondimensional, that is, not obtained from a Cartesian space representation. Rather, topological indices convey information representing significant aspects of molecular structure which do not require a 3D basis. 3D information is implicit in the topological description. For example, the 3D geometry of a molecule with three quaternary carbon atoms in the skeleton is rather different from one with methylene groups; a structure with six sp2 carbon atoms in a cycle is considerably different from an open chain with six sp3 carbon atoms. Thus, there is a significant implicit relation between topological indices and 3D geometry.

The structure indices produced in the Molconn software encode several features of molecular structure. The set of molecular connectivity indices (7-8) represents the molecule as a whole entity, encoding skeletal branching; adjacency and nonadjacency of groups; cyclic features; saturation, unsaturation, aromaticity; electronic distribution over skeletal structure; overall size. In our first book on connectivity, Monty Kier and I pointed out that chi indices form a representation for structure which permits a basis for comparison (9). In Chapter 10 we presented chi indices of heptane isomers as histograms to illustrate this point. Visual examination of the chi histograms gives clear discrimination of these isomers, including revelation of some patterns. The kappa indices were developed to give a more specific representation of molecular shape (10). Further developments have led to a useful index of flexibility (11,12). These chi and kappa indices along with other selected graph invariants (such as path counts) have been integrated into algorithms of molecular similarity for database searching (3,13). Based on the experiences reported by users, these topological descriptors are useful for characterization of chemical databases and molecular similarity indices.

A second important feature for the chemical diversity arena, in addition to creating an appropriate space for representation of molecular structures, is the ability to relate structure to biological activities and physicochemical properties. This is the arena of traditional QSAR. There is now a history of effective application of the chi and kappa and related indices to development of quality QSAR models (7-10,14-16). However, the chi and kappa indices represent whole molecules. In biological interactions, often part of a molecule or only a few atoms dominate the quantitative aspects of a model. Also, for physicochemical properties, it is helpful to represent separately the various atoms and groups in a structure-property model. For these reasons we developed the electrotopological state with its associated atom level (17), atom type (18-20) and bond type indices (1). These indices are proving to be powerful structure representations for QSAR and for database characterization because the E-state combines atomic electronic character which is important in molecular interactions with molecular topology. The E-state indices are a nonlinear combination of electronic and topological character of each atom, not a simple sum of atomic properties. In its atom type form, the E-state shows promise for database searching (19).

At this point in the development of molecular representations, the Molconn indices provide a broad and strong basis for approaching the problems arising in molecular diversity. The indices are directly computable at very high speed. The topological descriptors provide a basis for direct interpretation in terms of chemical structure. Finally, because of the demonstrated relation to biological and physicochemical properties, these indices do more than simply describe a space in which structures are reasonably distributed. That index space is truly a structure-activity space.

1. Molconn-Z, Hall Associates Consulting, 2 Davis Street, Quincy, MA and Molconn-Z 3.0S, Edusoft, LC, PO Box 1811, Ashland, VA, 23005.

2. D. J. Cummins, D. W. Andrews, J.A. Bentley, and M. Cory, J. Chem. Inf. Comput. Sci., 36, 750-763 (1996).

3. C. Cheng, G. Maggiora, M. Lajiness, and M. Johnson, J. Chem. Inf. Comput. Sci., 36, 909- 915 (1996).

4. R. D. Brown and Y. Martin, J. Chem. Inf. Comput. Sci., 36, 572-584 (1996).

5. C. A. Pepperell and P. Willett, J. Comput.-Aided Mol. Design, 5, 455-474 (1991).

6. J. Bradshaw and E. Meliski, Glaxo-Wellcome, private communication.

7. L. B. Kier and L. H. Hall, "Molecular Connectivity in Structure-Activity Analysis", Research Studies Press, John Wiley and Sons, Chichester, UK (1986).

8. L. H. Hall and L. B Kier, in Reviews of Computational Chemistry, Chap. 9, pp 367-422, eds D. Boyd and K Lipkowitz, VCH Publishers, Inc. (1991).

9. L. B. Kier and L. H. Hall, "Molecular Connectivity in Chemistry and Drug Research", Academic Press, New York (1976).

10. L. B. Kier, in Computational Chemical Graph Theory, chap. 6, pp 152-174, D. H. Rouvray ed., Nova Press, New York (1990).

11. L. B. Kier, Quant. Struct.-Act. Relat., 8, 218-221 (1989).

12. C.-W. von de Lieth, K. Stumpf-Nothof and U. Prior, J. Chem. Inf. Comput. Sci., 36, 711-716 (1996).

13. S. Basak, V. R. Magnuson, G. J. Niemi and R. R. Regal, Discrete Appl. Math, 19, 17-44 (1988).

14. R. Garcia-Domenech, F. J. Garcia-March, R. M. Soler, J. Galvez, G. M. Anton-Fos and J. V. Julian-Ortiz, Quant. Struct.-Act. Relat., 15, 201-207 (1996).

15. L. Pogliani, Current Topics in Peptide and Protein Research, 1, 119-134 (1994).

16. M. Skvortsova, I. I. Baskin, O. Slovkhotova, A. A. Palyulin and N. Zefirov, J. Chem. Inf. Comput. Sci., 33, 630-634 (1994)

17. L. B. Kier and L. H. Hall, in Advances in Drug Design, Vol. 22, B. Testa, ed., Academic Press (1992).

18. L. H. Hall and L. B. Kier, J. Chem. Inf. Comput. Sci., 35, 1039-1045, (1995).

19. L. H. Hall, L. B. Kier and B. B. Brown, J. Chem. Inf. Comput. Sci., 35, 1074-1080, (1995).

20. L. H. Hall and C. T. Story, J. Chem. Inf. Comput. Sci., 36, 1004-1014 (1996)

Lowell Hall, October 1996

Lowell H. Hall, Department of Chemistry, Eastern Nazarene College, Quincy, MA 02170

hall@enc.edu; FAX: +1-617-745 3425; PH/MSG +1-617-745 3549

Molecular Diversity and Molecular Representation by Topological Descriptors.

 

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In Memoriam R.W. (Bob) Taft passed away on 9th February 1996.

 

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The Journal QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS

This VCH journal is considered to be the "home" journal of THE QSAR AND MODELLING SOCIETY.

Preview: Quantitative Structure-Activity Relationships, 15, No. 5 (1996)

	R. Bureau, J. C. Lancelot, H. Prunier and S. Rault : Conformational Analysis and 3D QSAR Study on Novel Partial Agonistsof 5-HT3 Receptors
	Mourad Said, Claude Ziegler and Jaques Magdalou: Inhibition of Bilirubin UDP-Glucuronosyl Transferase: A Comparative Molecular Field Analysis (CoMFA)
	Supa Hannongbua, Luckhana Lawtrakul, Christoph A. Sotriffer and Bernd M. Rode: Comparative Molecular Field Analysis of HIV-1 Reverse Transcriptase in the Class of 1-(2-Hydroxyethoxy)-methyl-6-(phenylthio)-thymine
	Daniel Domine, James Devillers, Dietrich Wienke and Lutgarde Buydens: Test Series from Nonlinear Neural Mapping
	Raimund Mannhold and Karl Dross: Calculation Procedures for Molecular Lipophilicity: A Comparative Study.

 

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Meetings and Courses

1996

	Second One Day European Symposium on Ionisation, Partitioning and Lipophilicity. Frankfurt, Germany, December 14, 1996. Info: science@easynet.co.uk.
	Rational Drug Design, December 16-17, 1996. San Diego, USA. Contact: IBC, FAX +1-508-481 7911 (reg@incusa.com).

1997

	ACS Meeting, San Francisco, April 13-17, 1997. Topics of interest: - Information needs for planning ans synthesis of combinatorial libraries - Clustering and similarity searching techniques for studying molecular diversity - Data mining and data visualization Contact: Dr. Wendy A. Warr (FAX +44-1477-533837; waw@xtrn.org; http://www.warr.com) - Symposium on Pharmacophore Mapping (contact: Dr. Yvonne Martin, yvonne.c.martin@abbott.com)
	Trends in Drug Research, Noordwijkerhout, May 11-16, 1997. Contact: Prof. H. Timmerman (fax +31-20-4447610, bijloo@chem.vu.nl)
	Gordon Research Conference on Quantitative Structure-Activity Relationships (1997). Programme-chair: Dr. Gerry Maggiora (gmmaggio@pwinet.upj.com). Chairman: Dr. Herschel Weintraub (h.weintraub@helios-pharma.com).
	Quantitative Modeling Approaches for Understanding and Predicting Mutagenicity and Carcinogenicity, September 3-5, 1997, Rome, Italy. Contact: R. Begnini, FAX +39-6-49387073 (Calicc@pop3.iss.it).
	British Pharmaceutical Conference, September 15-18, 1997. Scarborough, UK. Info: John Dearden (phajdear@livjm.ac.uk)

1998

12th European Symposium on Quantitative Structure-Activity Relationships: Molecular Modelling and Prediction of Bioactivity, August 23-28, 1998, Copenhagen, Denmark. Contact: Dr. Klaus Gundertofte (fax +45-36-301385). http://compchem.dfh.dk/qsar98/.

 

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Books

	H.-J. Böhm, G. Klebe und H. Kubinyi, Wirkstoffdesign. Der weg zum Arzneimittel (in German), Spektrum (1996) ·
	Charton, M. (Ed.), Advances in Quantitative Structure-Property Relationships, Vol. 1, JAI Press, Greenwich CT (1996)
	N. C. Cohen, Ed., Guidebook on Molecular Modelling in Drug Design, Academic Press, London, (1996)
	J. Devillers, Ed., Genetic Algorithms in Molecular Modelling, Academic Press, London (1996)
	J. P. Doucet and J. Weber, Computer-Aided Molecular Design, Academic Press, London (1996)
	Ford, M.G., Greenwood, R., Brooks, G.T. and Franke, R., (Eds.) Bioactive Compound Design: Possibilities for industrial use. SCI Bios Scientific Publishers (1996)
	Höltje, H.-D. and Folkers, G., Molecular Modeling - Basic Principles and Applications, VCH, Weinheim (1996). Vol. 5 of Methods and Principles in Medicinal Chemistry · P.
	Krogsgaard-Larsen, T. Liljefors and U. Madsen, Eds., A Textbook of Drug Design and Development, 2nd Edition, Harwood Academic Publishers, Amsterdam (1996)
	A. R. Leach, Molecular Modelling. Principles and Applications, Addison Wesley Longman, Essex, UK (1996)
	Pliska, V., Testa, B. and Van de Waterbeemd, H., Lipophilicity in Drug Action and Toxicology, VCH, Weinheim (1996). Vol. 4 of Methods and Principles in Medicinal Chemistry
	Van de Waterbeemd, H. (Ed.) Structure-Property Correlations in Drug Research, Landes, Austin & Academic Press, London (1996)
	Wermuth, C.G. (Ed.) The Practice of Medicinal Chemistry, Academic Press, London (1996)
	Hansch, C. and Fujita, T. (Eds.) Classical and Three-Dimensional QSAR in Agrochemistry, ACS Symposium Series 606, Washington (1995).
	Fujita, T. (Ed.) QSAR and Drug Design: New Developments and Applications, Pharmacochemistry Library Vol. 23, Elsevier (1995)
	P. M. Dean, G. Jolles and C. G. Newton, Eds., New Perspectives in Drug Design, Academic Press, London (1995)
	J. M. Goodfellow, Ed., Computer Modelling in Molecular Biology, VCH, Weinheim (1995)
	E. C. Herrmann and R. Franke, Computer Aided Drug Design in Industrial Research, Ernst Schering Research Foundation Workshop 15, Springer-Verlag, Berlin (1995)
	M. E. Wolff, Ed., Burger's Medicinal Chemistry, 5th Edition, Volume I, John Wiley & Sons, New York (1995)

 

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SOFTWARE

WHIM-3D, 3D - molecular descriptors for QSAR studies.

The WHIM descriptors (Weighted Holistic Invariant Molecular descriptors) are 3D-molecular descriptors recently proposed by the Research Group on Chemometrics of Prof. Roberto Todeschini (Dept. of Environmental Sciences of the University of Milan - Italy).

The descriptors interpretability and high capability to model several physico-chemical properties and biological activities open new perspectives in QSAR studies, also for classes of heterogeneous compounds. The invariance to roto-translation of the WHIM descriptors avoids any problems related to the alignment of molecules and the comparison of non-congeneric compounds.

At present, the package WHIM - 3D / QSAR (version 1.0) for the calculation of the WHIM descriptors is available, free of charge. This software calculates the WHIM descriptors from (x,y,z) atomic coordinates of a molecule, for HyperChem (.HIN) and Tripos (.MOL2) file formats. The WHIM - 3D /QSAR package is directly available on request to:

TALETE srl, via Pisani, 13 - 20124 Milano (Italy)

tel./fax.: +39 - 2 - 66981300

or

Prof. Roberto Todeschini, Dept. Environmental Sciences - via Emanueli 15.

I-20126 Milano (Italy)

fax: +39 - 2 - 64474307 - Email: tode@alpha.disat.unimi.it

[1] Todeschini, R., Lasagni, M. and Marengo E., J.Chemometrics, 8, 263 - 272 (1994).

[2] Todeschini, R., Gramatica, P. and Provenzani, R., Chemometrics and Intell. Lab. Systems, 27, 221 - 229 (1995).

[3] Todeschini, R., Bettiol, C., Giurin, G., Gramatica, P., Miana P., and Argese, E., Chemosphere, 33, 71 - 79 (1996).

[4] Todeschini, R., Vighi, M., Provenzani, R., Finizio, A. and Gramatica, P., Chemosphere, 32, 1527 - 1545 (1996).

[5] Todeschini, R. and Gramatica, P., Quant. Struct.-Act. Relat., Part 3., submitted.

[6] Todeschini, R. and Gramatica, P., Quant. Struct.-Act. Relat., Part 4., submitted.

Complete information about H-bonding strength of chemical compounds is available on your desktop by means of HYBOT (HYdrogen BOnd Thermodynamics)Program Package

There are three commercial available programs: HYBOT-96.Data Base, HYBOT-96.Factor and HYBOT-96.Complete Set.

HYBOT-96.Data Base contains chemical structures, experimental thermodynamical (DH and/or DG) and spectral parameters of 12,030 hydrogen bond complexes of 650 H-bond donors and 2,250 H-bond acceptors in 64 solvents and gas phase together with attendant information. All H-bond donor and H-bond acceptor centres are identified and marked.

HYBOT-96.Factor has two modules. The first one contains unique database of enthalpy (E), free energy (C) and binding (a or b) factor values for 440 H-bond donors and 1,915 H-bond acceptors. All factors are calculated on the basis of experimental data (from HYBOT-96.Data Base) by means of multiplicative approach and quantitatively characterizes H-bond strength of compounds.

The second module of HYBOT-96.Factor contains the computer program for calculation H-bond donor and H-bond acceptor factor values of marked atoms in any new compound. Predicting procedure is based on the search of the nearest neighbour in data base of factor values (from the first module) and is carried out by means of fragmentation of molecules with the subsequent analysis of structural environtment of atoms.

HYBOT-96.Complete Set contains all three above-mentioned modules inside of the common shell.

Operating system: Windows 3.1 or later. Minimum hardware configuration required: IBM PC AT 386/387, 4 Mb RAM, hard disk 8 Mb free, VGA, Microsoft mouse.

Literature:

	O.A.Raevsky, V.Ju.Grigor’ev , D.B.Kireev and N.S.Zefirov.“Complete Thermodynamic Description of H-Bonding in the Framework of Multiplicative Approach“, Quant.Struct.- Act.Relat. 11. 49-63 (1992).
	O.A.Raevsky, V.Ju.Grigor’ev, V.P.Solov’ev.“ Drug Design H-bond scale“. in „QSAR Rational Approaches to the Design of Bioactive Compounds „. Eds.C.Silipo and A.Vittoria, Elsevier. Amsterdam. 135-138 (1991).
	O.A.Raevsky,V.Ju.Grigor’ev and E.Mednikova. „QSAR H-bond Descriptions“. in Trends in QSAR and Molecular Modelling 92. Ed. C.G.Wermuth. ESCOM. Leiden.116-119 (1993).
	O.Raevsky, V.Ju.Grigor’ev, D.B.Kireev and N.S.Zefirov.“Correlation Analysis and H-bond Ability in framework of QSAR“.J.Chim.Phys. et Phys.- Chem. Biol. 89. 1747- 1753 (1992).
	H-.J.Schneider, V.Rudiger and O.Raevsky. „The Incrimental Description of Host-Guest Complexes“. J.Org.Chem. 58.3648-4853 (1993).
	O.A.Raevsky, K.-J.Schaper and J.K.Seydel. „H-bond contribution in Octanol-Water Parrtition Coefficients of Polar Compounds“.Quant.Struct.-Act.Relat. 14. 433-436 (1995).
	O.Raevsky, L.Dolmatova and V.Grigor’ev.“ Molecular Recognition Descriptors in QSAR“.in QSAR and Molecular Modelling:Concepts, Computational Tools and Biological Applications. Eds.F.Sanz, J.Giralo, F.Manaut.Prous.Barcelona. 241-245 (1995).

Detailed information and price list:

Prof.O.Raevsky, Dr.V.Grigor’ev, Institute of Physiologically Active Compounds of Russian Academy of Sciences, 142432, Chernogolovka, Moscow region, Russia

Fax: 007-095-302-91-59

E.mail:raevsky@ipac3.sherna.msk.su

Internet:raevsky@ipac.ac.ru

 

Miscellaneous

The Society is still growing........!

in preparation: Van de Waterbeemd, H., Testa, B. and Folkers, G. (Eds.), Computer-Assisted Lead Finding and Optimization, Verlag Helvetica Chimica Acta, Basel (1996/1997)

Contributions to the Newsletter :

All members are invited to contribute to the content of our Newsletter. This Newsletter shall not be a one-man show, it gains from your experience. Our publishing policy will not allow us to accept scientific contributions which better should be sent to a reviewed journal. However, tips and tricks, key references, conferences, books, shareware, even the announcement of new commerical software, are welcome. We depend on your active participation!

Please send your comments and contributions to

Han van de Waterbeemd c/o F.

Hoffmann-La Roche Ltd.

PRPC, 65/314

CH-4002 Basel, Switzerland

FAX +41-61-688 1075

E-MAIL johannes.van_de_waterbeemd@roche.com

IMPORTANT

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The QSAR and Modelling Society - The QSAR and Modelling Society - The QSAR and Modelling Society

Last Updated: March 15, 2001

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