RESOURCE - RELATED RESEARCH COMPUTERS AND CHEMISTRY (RR-00612 COMPETING RENEWAL APPLICATION) Submitted to BIOTECHNOLOGY RESOURCES BRANCH OF THE NATIONAL INSTITUTES OF HEALTH May, 1976 DEPARTMENTS OF CHEMISTRY, GENEICS, AND COMPUTER SCIENCE STANFORD UNIVERSITY DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE PUBLIC HEALTH SERVICE Form Approvrd SECTION I O.Y.B. 68-Ro249 LEAVE BLANK TYPE PROGRAM NUMBER GRANT APPLICATION L REVIEW GROUP couby3 L fhfonrh, VIIll FORMERLY DATE RECEIVED I TO BE COMPLETED BY PRINCIPAL INVESTIGATOR l/rem5 f rhroue 7and ISAl 1. TITLE OF PROPOSAL (00 nor exceed 5.3 typewriter spaces) RESOURCE-RELATED RESEARCH - COMPUTERS ANC 2. PRINCIPAL INVESTIGATOR 2A. NAME (Last, First. Initial) Djerass i , Carl 28. TITLE OF POSITION Professor of Che,mrstry 2C. MAILING ADDRESS /Safe@ City, Srate, iflp . Code) Department of Chemistry Stanford University Stanford, California 94305 ' ,_ .. 30. DEGREE Ph.D. 2E. SOCIAL SECURftY NO. (Scs Insvucdond -- Department of Chemistry 2H. MAJOR SUBDIVISION ISae lmfructions~ Department of Humanities and Sciences 7. Research Involving Human Subjects ISee 7nsrruc(ions) Ma NO 0.0 YES Approvsd: C. 0 YES - Pending Review ba1* TO BE COMPLETED BY RESPONSIBLE ADMINISTRATIVE AUTHORI' 9. APPLICANT ORGANIZATION(S) /See Imlrucrions) Stanford University Stanford, California 94305 IRS No. g4-1156365 ' Congressional District Nd. 12 I ChEM t STRY 10. NAME, TITLE, AND TELEPHONE NUMBER OF OFFICIALIS) SIGNING FOR APPLICANT ORGANIZATION(S) c/o Sponsored Pr Telephone Number (~1 15. CERTIFICATION AND ACCEPTANCE. We, rho undanigned. cart8 I-DATES OF ENTIRE PROPOSED PROJECT PE.RIOD ffhis o pplicarion. CROM THROUGH s/1977 4/1982 4. TOTAL DIRECT COSTS RE- 5. DIRECT COSTS REQUESTED OUESTED FOR PERIOD IN FOR FIRST 12.MONTH PE RlOC ITEM 3 $1,463,940 $250,650 6. PERFORMANCESITE tSec /mrrucrions/ Department of Genetics, Department of Chemistry, and Department of Computer Science Stanford Un ivers i ty 1. lnvcntions [Renewal Apphcants dnly - S*e h~rocmul Am NO B.a YES - Not previously reported C.aYES - Previously rep~rf~ f (Items 8 through 13 and f 581 Il. TYPE OF ORGANIZATION (Check applicrble ir8ml 0 FEDERAL 0 STATE 0 LOCAL tZ3 OTHER ISpucW Private, non-Drofit Uajver 4 I,. S. OOVF.RHMENT PRWTING OF'I;I'?E : 1974 SW.-ES/3094 EDWARD A. FElGENBAUM Selected Papers, 1965-76 I . J. I.ederberg and E. A. Feigenbaum, "Mechanization of in Organic Chemistry", in B. Klelnmuntz (ed.), Formal Human Judgment, (Wiley, 1968). (Also Stanford Artifi Project Memo No. 54, August 1967). 2. J . Lederberg , G. L. Sutherland, 8. G. Buchanan, E. A. Bibliography Inductive Inference Representat ions for cial Intelligence Fe i genbaum, A. V. Robertson, A. M. Duff ield, and C. Djerass i , "Applications of Artificial Intel 1 igence for Chemical inference I. The Number of Possible Organic Compounds: Acyclic Structures Containing C, H, 0 and N". Journal of the American Chemical Society, 91 :ll (May 21, 1969). 3. B. G. Buchanan, G. L. Sutherland, E. A. Feigenbaum, "Toward an Understanding of Information Processes of Scientific Inference in the Context of Organic Chemistry", in Machi.ne Intelligence 5, (B. Meltter and D. Michie, eds.) Edinburgh University Press (1970). (Also Stanford Artificial Intelligence Project Memo No. 99, September 1969.) 4. E. A. Feigenbaum, B. G. Buchanan, Problem Solving: A Case Study Usi Intel1 igence 6 (B. Mel'tzer and D. (1971). (Also Stanford Arttficlal 5. B. G. Buchanan, E. A. Feigenbaum, and J. Lederberg, "On General i ty and ng the DENDRAL Program". In Machine Michie, eds.) Edinburgh University Press Intelligence Project Memo No. 131.) and J. Lederberg, "A Heuristic Programming Study of Theory Formation in Science." In Proceedings of the Second International Joint Conference on Artificial Intelligence, lmperlal College, London (September, 1971). (Also Stanford Artificial Intelligence Project Memo No. 145.) 6. B. G. Buchanan, E. A. Feigenbaum, and N. S. Sridharan, "Heuristic Theory Formation: Data Interpretation and Rule Formation". In Machine Intelligence 7, Edinburgh University Press (1973). 7. D. H. Smith, B. G. Buchanan, W. C. White, E. A. Feigenbaum, C. Djerassi and J . Lederberg , "Applications of Artificial Intelligence for Chemical Inference X. INTSUM. A Data Interpretation Program as Applied to the Collected Mass Spectra of Estrogenic Steroids". Tetrahedron, 29, 3117 (1973). 8. E. A. Feigenbaum, "Computer Appl ications: Introductory Remarks ,`I in Proceedings of Federation of American Societies for Experimental Biology, Vol. 33, No. 12 (Dec., 1974) 2331-2332. Other papers in Information Processing Psychology (18) Books and Monographs I. Computers and Thought, co-editor wfth Julian Feldman, McGraw-Hill, 1963. 2. Information Processing Language V Manual, Englewood Cliffs, N.J., Prentice-Hall, 1961 (with A. Newell, F. Tonge, G. Mealy, et.al.). 3. An Information Processing Theory of Verbal Learning, Santa Monica, The RAND Corporation Paper P- 1817, October 1959 (monograph) . RESEARCH SUPPORT AND PENDING APPLICATIONS: Edward A. Fefgenbaum Agency: Advanced Research Projects Agency Contract Number: DAHC 15 73 C 0435 Title of Contract: Heuristic Programming Project Period of Contract: July 1975-June 1977 Annual Budget Level: $203,000 Fraction of time committed: 40% Academic Yr. Agency: National Science Foundation Grant Number: MCS 76-11649 Title of Grant: MOLGEN: A Computer Science Application to Molecular Genetics Period of Grant: 6/l/76-5/31/78 Annual Budget Level: $110,700 (2 yr. amount) Fraction of time committed: 10% Academic Yr.; 100% Summer PENDING: Agency: National Library of Medicine Title: Training Program in Biomedical Computing Period: 6/77-5/Q Annual Budget Level: $334,193 (direct cost) Fraction of time committed: 20% SECTION II - PRIVILEGED COMMUNICATION BIOGRAPHICAL SKETCH (Give the following Information for allprofassional parsonnd listed on page 3, bq$nnIq with the PrinciPal fnvmt&tofi tha continuatim page and follow tha mma ganerrl format for each penon) UAME TITLE * BIRTHDATE (Ma. Day, Yr.) BRUCE G. BUCHANAN Adjunct Professor 7-7-40 PLACE OF BIRTH hZity, State, Country) PRESENT NATIONALITY (If nonUS citizen. SEX Ind;catv kind of visa and expiration date) St. Louis, Missouri, U.S.A. U.S. citizen KiIhblO 0 Fomalr EDUCATION (Llqin wirh bacealaureats training and includepostdoctoral~ SCIENTIFIC INSTITUTION AND LOCATION DEGREE YEAR CONFERRED FIELD Ohio Wesleyan University B.A. 1961 Mathemat its Michigan State University M.A. 1966 Philosophy Michi.gan State University Ph.D. 1966 Philosophy "oNo%cipient of National Institutes of Health Career Development Award (1971-1976); Invited Speaker: 1975 NATO Advanced Study Institute on Machine Representation of Knowledge; 1974 Gordon Conference on Scientific Information Problems in Research. MAJOR RESEARCH INTEREST ROLE IN PROPOSED PROJECT Associate Investigator RESEARCH SUPPORT (SH hswuctionrl RESEARCH ANDmR PROFESSIONAL EXPERIENCE (Starting withprmnr position,&JCgi&gandexpstiencrr~ffant toarea ofpro@C Lirtaff or mat mpmntwdvr publicotiorrr Do not ucaed 3 pages for uch individual.) 1976 - Adjunct Professor, Computer Science Department Stanford University, Stanford, California 1972-1976 Research Computer Scientist, Computer Science Department Stanford University, Stanford, California 1966-1971 Research Associate, Artificial Intelligence Project Stanford University, Stanford, California IllI4 398 (FORMERLY PHS 398) Rsv. 1173 t ". 9. GOVERNMENT PRINTING OFi;lCE : 1974 5842X3/- BRUCE G. BUCHANAN Selected Publications: Bibliography I . B. G. Buchanan, "Applications of Artificial Intelligence to Scientific Reasoning." In Proceedings of Second USA-Japan Computer Conference, August, 1975. 2. E. H. Shortliffe, R. Davis, S. G. Axllne, B. G. Buchanan, C. C. Green, and S. N. Cohen, "Computer-Based Consultations in Clinical Therapeutics: Explanation and Rule Acquisition Capabilities of the MYCIN System," Computers and Biomedical Research, 8, 303-320 (1975). 3. E. H. Shortliffe and B. G. Buchanan, "A Model of Inexact Reasoning in Medicine", Mathematical Biosciences, 23, 351-379 (1975). 4. D. Michie and B. G. Buchanan, "The Scientist's Apprentice" in Computers for Spectroscopy (ed. R.A.G. Carrington) London: Adam Hilger, 1974. 5. B. G. Buchanan and N. S. Sridharan, "Rule Format ion on Non-Homogeneous Classes of Objects". Proceedings of the Third international Joint Conference on Artificial Intelligence (1973). 6. D. H. Smith, B. G. Buchanan, W. C. White, E. A. Feigenbaum, C. DJerassi, and J. Lederberg, "Applications of Artificial Intel 1 igence for Chemical Inference X. Intsum. A Data Interpretation Program as Applied to the Collected Mass Spectra of Estrogenic Steroids". Tetrahedron, 29, 3117 (1973). 7. D. H. Smith, B. G. Buchanan, R. S. Engelmore, H. Aldercreutz and C. Djerass i , "Applications of Artificial Intelligence for Chemical Inference IX. Analysis of Mixtures Without Prior Separation as I1 lustrated for Estrogens". Journal of the American Chemical Society. 95, 6078, 1973. 8. B. G. Buchanan, Review of Hubert Dreyfus' "What Computers Can't Do: A Critique of Artificial Reason", Computing Reviews (January, 1973). 9. B. G. Buchanan, E. A. Feigenbaum and N. S. Sridharan, "Heuristic Theory Format ion: Data Interpretation and Rule Formation". Machine Intelligence 7, Edinburgh University Press (1972). 10. C. W. Churchman and B. G. Buchanan, "On the Design of Inductive Systems: Some Phi losophical Problems". British Journal for the Philosophy of Science, 20 (1969), 311-323. 11 . 8. G. Buchanan, G. L. Sutherland, E. A. Feigenbaum, "Toward an Understanding of Information Processes of Scientific Inference in the Context of Organic Chemistry", Machine Intelligence 5 (B. Meltzer and D. Michie, eds.), Edinburgh University Press (1970). (Al so Stanford Artificial Intelligence Project Memo No. 99, September 1969.) RESEARCH SUPPORT AND PENDING APPLICATIONS: Bruce G. Buchanan Agency: Advanced Research Projects Agency Contract Number: DAHC 15 73 C 0435 Title of Contract: Heuristic Programming Project Period of Contract: July 1975-June 1977 Annual Budget Level: $203,000 Fraction of time committed: 25% Agency: National Science Foundation Grant Number: MCS 76-11649 Title of Grant: MOLGEN: A Computer Science Application to Molecular Genetics Period of Grant: 6/l/76-5/31/78 Annual Budget Level: $110,700 (2 yr. amount) Fraction of time committed: 25% PENDING: Agency: National Library of Medicine Title: Training Program in Biomedical Computing Period: 6/77-5/82 Annual Budget Level: $334,193 (direct cost) Fraction of time committed: 20% c SECTION II - PRIVILEGED COMMUNICATION BIOGRAPHICAL SKETCH (Give the following information for all professional personnel listed on page 3, beginning with the Principal Jnves tigator. Use continuation pages and follow the same general format for each person.1 - NAME TITLE BIRTHDATE (Ma. Day, Yr.) Dennis H. Smith Research Associate 11/12/42 PLACE OF BIRTH ICity, State, Countryl PRESENT NATIONALITY (If non-U..!2 citizen, SEX indicate kind of visa and expiration dare) New York USA b Male .`fi Female E D UCAT I ON (Begin with bJCCahJlCa te training and indude postdoc torail INSTITUTION AND LOCATION DEGREE YEAR SCIENTIFIC CONFERRED FIELD Massachusetts Inst. of Technology Cambridge, Mass. S.B. 1964 Chemistry University of California, Berkeley Berkeley, California Ph.D. 1.967 Chemistry HONORS Alfred P. Sloan Foundation Scholarship NASA Predoctoral Traineeship Phi Lambda Upsilon, Sigma Xi MAJOR RESEARCH INTEREST ROLE IN PROPOSED PROJECT Mass Spectrometry and A.I. in Chemistry Research Associate RESEARCH SUPPORT (Seeinstructions) N/A , -- RESEARCH AND/OR PROFESSIONAL EXPERIENCE (Starting withpresentposition, list traininqand experience zant to area ofprl?jjict List a:1 or most representative publications. Do not exceed 3 pages for each individual.) 1971-Present Research Associate, Stanford University, Stanford,Ca. 1970-1971 Visiting Scientist, University of Bristol, Bristol, England 1967-1970 Assistant Research Chemist, University of Calif.at Berkeley, Berkeley, Ca. 1965-1967 NASA Pre-Doctoral Traineeship, University of Calif.at Berkeley,Berkeley, Ca. Publications: See attached list. HHS398 Rev. 3-70 - DENNIS H. SMITH Selected Publications 1. H.G. Langer, R.S. Gohlke, and D.H. Smith, "Mass Spectrometric Differential Thermal Analysis," Anal. Chem., 37, 433 (1965). 2. S.M. Kupchan, J.M. Cassady, J.E. Kelsey, H.K. Schnoes, D.H. Smith, and A.L. Burlingame, "Structural Elucidation and High Resolution Mass Spectrometry of Gaillardin, 5292 (1966) . a New Cytotoxic Sesquiterpene Lactone," J. Amer. Chem. Sot., 88, 3. D.H. Smith, Ph.D. Thesis, "High Resolution Mass Spectrometry: Techniques and Applications to Molecular Structure Problems," Dept. of Chemistry, University of California, Berkeley, California {1967). 4. H.K. Schnoes, D.H. Smith, A.L. Burlingame, P.W. Jeffs, and W. Dopke, "Mass Spectra of Amaryllidaceae Alkaloids: 2825 (1968). The Lycorenine Series," Tetrahedron, 2, 5. A.L. Burlingame, D.H. Smith, and R.W. Olsen, "High Resolution Mass Spectrometry in Molecular Structure Studies. XIV. Real-time Data Acquisition, Processing and Display of High Resolution Mass Spectral Data," Anal. Chem., 5, 13 (1968). 6. A.L. Burlingame and D.H. Smith, "High Resolution Mass Spectrometry in Molecular Structure Studies. II. Automated Heteroatomic Plotting as an Aid to the Presentation and Interpretation of High Resolution Mass Spectral Data," Tetrahedron,, 24, 5749 (1968). 7. W.J. Richter, B.R. Simoneit, D.H. Smith, and A.L. Burlingame, "Detection and Identification of Oxocarboxylic and Dicarboxylic Acids in Complex Mixtures by Reductive Silylation and Computer-Aided Analysis of High Resolution Mass Spectral Data," Anal. Chem., 41, 1392 (1969). 8. The Lunar Sample Preliminary Examination Team, "Preliminary Examination of Lunar Samples from Apollo 11," Science, l& 1211 (1969). 9. S.M. Kupchan, W.K. Anderson, P. Bollinger, R.W. Doskotch, R.M. Smith, J.A. Saenz-Renauld, H.K. Schnoes, A.L. Burlingame, and D.H. Smith, "Tumor Inhibitors. XXXIX. Active Principles of Acnistus arborescens. Isolation and Structural and Spectral Studies of Withaferin A and Withacnistin," J. Org. Chem., 2, 3858 (1969).. 10. A.L. Burlingame, D.H. Smith, T.O. Merren, and R.W. Olsen, "Real-time High Resolution Mass Spectrometry," in Computers in Analytical Chemistry (Vol. 4 in Progress in Analytical Chemistry series), C.H. Orr and J. Norris, Eds., Plenum Press, New York, 1970, pp. 17. 11. The Lunar Sample Preliminary Examination Team, "Preliminary Examination of Lunar Samples from Apollo 12," Science, 167, 1325 (1970). 12. D.H. Smith, "Mass Spectrometry," Chapter X in Guide to Modern Me Instrumental Analysis, T.M. GOUW, Ed., Wiley-Interscience, New York, 13. D.H. Smith, R.W. Olsen, F.C. Walls, and A.L. Burlingame, "Real-t Spectrometry: LOGOS--A Generalized Mass Spectrometry Computer System and Low Resolution, GC/MS and Closed-Loop Applications," Anal. Chem., (1971). i hods of 972. me Mass for High 43, 17% DENNIS H. SMITH Selected Publications, P. 2 14. A.L. Burlingame, J.S. Hauser, B.R. Simoneit, D.H. Smith, K. Biemann, N. Mancuso, R. Murphy, D.A. Flory, and M.A. Reynolds, "Preliminary Organic Analysis of the Apollo 12 Cores," Proceedinqs of the Apollo 12 Lunar Science Conference, E. Levinson, Ed., M.I.T. Press, Cambridge, Mass., 1971, p. 1891. 15. D.H. Smith, "A Compound Classifier Based on Computer Analysis of Low Resolution Mass Spectral Data," Anal. Chem., 44, 536 (1972). 16. D.H. Smith and G. Eglinton, "Compound Classification by Computer Treatment of Low Resolution Mass Spectra-Application to Geochemical and Environmental Problems," Nature, 235, 325 (1972). 17. D.H. Smith, N.A.B. Gray, C.T. Pillinger, B.J. Kimble, and G. Eglinton, "Complex Mixture Analysis - Geochemical and Environmental Applications of a Compound Classifier Based on Computer Analysis of Low Resolution Mass Spectra," Adv. in Org. Geochem., 1971, p. 249. 18. P. Longevialle, D.H. Smith, H.M. Fales, R.J. Highet, and A.L. Burlingame, "High Resolution Mass Spectrometry in Molecualr Structure Studies. V. The Fragmentation of Amaryllis Alkaloids in the Crinine Series," Org. Mass. Spectrom., 1, 401 (1973). 19. B.R. Simoneit, D.H. Smith, G. Eglinton, and A.L. Burlingame, "Applications of Real-time Mass Spectrometric Techniques to Environmental Organic Geochemistry. II. San Francisco Bay Area Waters," Arch. Env. Contam. Tox., 1, 193 (1973). 20. G. Loew, M. Chadwick, and D.H. Smith, "Applications of Molecular Orbital Theory to the Interpretation of Mass Spectra. Prediction of Primary Fragmentation Sites in Organic Molecules," Org. Mass Spectrom., 1, 1241 (1973). 21. J.H. Block, D.H. Smith and C. Djerassi, "Mass Spectrometry in Structural and Stereochemical Problems, CCXXXVIII. The Effect of Heteroatoms upon the Mass Spectrometric Fragmentation of Cyclohexanones," J. Org. Chem., 39, 279 (1974). 22. D.H. Smith, C. Djerassi, K.H. Maurer, and U. Rapp, "Mass Spectrometry in Structural and Stereochemical Problems. CCXLII. Analysis of Mixtures Based on the Distribution of Fragment Ions Arising from Unimolecular Decomposition of Metastable Parent Ions," J. Amer. Chem. Sot., 96, 3482 (1974). 23. D.H. Smith, "The Scope of Structural Isomerism," J. Chem. Inf. Comp. Sci., 15, 203 (1975). 24. B.R. Simoneit, D.H. Smith, and G. Eglinton, "Application of Real-Time Mass Spectrometric Techniques to Environmental Organic Geochemistry. I. Computerized High Resolution Mass Spectrometry and Gas Chromatography-Low Resolution Mass Spectrometry," Arch. Environ. Cont. Tax., 2, 385 (1976). 25. T.R. Varkony, R.E. Carhart, and D.H. Smith, "Computer-Assisted Structure Elucidation. Modelling Chemical Reaction Sequences Used in Molecular Structure Problems," in "Computer-Assisted Organic Synthesis," W.T. Wipke, Ed., American Chemical Society, Washington, D.C., in press. DENNIS H. SMITH Selected Publications, P. 3 26. D.H. Smith and R.E. Carhart, "Structural Isomerism of Mono- and Sesquiterpenoid Skeletons ,`I Tetrahedron, in press. 27. L.L. Dunham, C.A. Henrick, D.H. Smith, and C. Djerassi, "Mass Spectrometry in Structural and Stereochemical Problems. CCXLVI. Electron Impact Induced Fragmentation of Juvenile Hormone Analogs," Orq. Mass Spectrom., in press. See also Bibliography. SECTION II - PRIVILEGED COMMUNICATION BIOGRAPHICAL SKETCH (Give the following Infomwdon for o ll profsrrionJl personnel listed on pqe 3, bspinnlq 4th the Pr/n&Jt Invati@etw. tke contfnuetion pags end follow the some pJnerJ1 formet for Jech person) PlAME TITLE ' BIRTHDATE IMa, LIey, Yr.) RAYMOND EDGAR CARHART RESEARCH ASSOCIATE 1 o/4/46 PLACE OF BIRTH Icky, Stete, CountryJ PRESENT NATIONALITY (If non-US cltkwt. IndicJte kind of viu Jml expire don de te) SEX Evanston, Illinois, U.S.A. U.S. citizen I F3J Mdr 0 Femnlr EDUCATION /Be& with bJccJlJurwte trainin@ Jnd include partdcctorell tNSTlTUTlON AND LOCATION DEGREE YEAR SCIENTIFIC CONFERRED FIELD Northwestern University B.A. 1968 Chemistry California Institute of Technology Ph.D. 1973 Physical Organic Chemistry HONORS Phi Beta Kappa; Sigma Xi; Phi Lambda Upsilon; NSF pre-doctoral fellowship 1968-72; NIH post-doctoral fellowship 1972-74. MAJOR RESEARCH INTEREST ROLE IN PROPOSED PROJECT Applications of Computer Science to Research Associate Organic Chemistry RESEARCH SUPPORT he insfrvcbbd N/A RESEARCH ANDX)R PROFESSIONAL EXPERIENCE (St~rtino wfthpr~ntposition,~Jndexpe'mcerdwent tOJmJofprow: fiftJf/ or most reprwent&ve publiutionr Do not excM3 w for&h individwl.) 1974- Research Associate, Department of Computer Science, Stanford University 1972-1974 NIH Post-doctoral Fellow, Department of Computer Science, Stanford University 196g(summer) Visiting Scientist, IBM Research Laboratory , Recent Publications: R. Carhart and C. Djerassi, "Applications of Artificial I Chemical inference Xl: The Analysis of Cl3 NMR Data for of Acyclic Amines", Journal of the Chemical Society (Per k San Jose, California ntelligence for Structure Elucidation in II), 1753 (1973). L. Masinter, N.S. Sridharan, R. Carhart and D.H. Smith, "Applications of Artificial Intelligence for Chemical Inference. XIII. Labeling of Objects Having Symmetry". Journal of the American Chemical Society, 96, 7714 (1974). R. E. Carhart, D. H. Smith, H. Brown and N. S. Sridharan, "Applications of Artificial Intelligence for Chemical Inference. XVI. Computer Generation of Vertex Graphs and Ring Systems". Journal of Chemical Information and Computer Science, 15, 124 (1975). R. E. Carhart, D. H. Smith, H. Brown and C. Djerassi, "Applications of Artificial Intelligence for Chemical Inference. XVII. An Approach to Computer-Assisted Elucidatior of Molecular Structure". Journal of the American Chemical Society, 97, 5755 (1975). YIH 398 (FORMERLY PHS 398) Rev. 1173 e ". S. GOVERNMENT PRINTING OFFICE : 1974 5842Y/- RAYMOND E. CARHART RECENT PUBLICATIONS R. E. Carhart, S., M. Johnson, D. H. Smith, B. G. Buchanan, R. G. Dromey, J. Lederberg, "Networking and a Collaborative Research Community: A Case "Computer Networking and Chemistry", iety, Washington, D.C., 1975, p. 192. Study Using the DENDRAL Program," in P. Lykos, Ed., American Chemical Sot R. E. Carhart and D. H. Smith, "Appl Chemical Inference. XX. 'Intelligent Structure Elucidation," Computers in ications of Artificial Intelligence for ' Use of Constraints in Computer-Assisted Chemistry, in press. T. R. Varkony, R. E. Carhart, and D. H. Smith, "Computer-Assisted Structure Elucidation. Modelling Chemical Reaction Sequences Used in Molecular Structure Problems," in "Computer-Assisted Organic Synthesis," W. T. Wipke, Ed., American Chemical Society, Washington, D.C., in press. D. H. Smith and R. E. Carhart, "Structural Isomerism of Mono- and Sesquiterpeno Skeletons," Tetrahedron, in press. id R. E. Carhart, "A Model-Based Approach to the Teletype Printing of Chemical Structures," Journal of Chemical Information and Computer Science, in press. I SECTION II -PRIVILEGED COMMUNICATION BIOGRAPHICAL SKETCH (Glvr tlw following InformNion for rllprofarrional personnel llrtsd on me 3, bsglnnlw 4th thr Princl~l Invatigltor. Use contfnuation p1oa and follow the swmr gw~rwl format for each ponoa) NAME TITLE * BIRTHDATE (Ma. Dmy, Yr.J Gretchen Maria SCHWENZER Research Associate 2/6/49 PLACE OF BIRTH [City, State, Countryj PRESENT NATIONALITY 111 non4.S cltizm, SEX indiwn kind of visa and expiration date) Buffalo, New York, U.S.A. U.S. 0 Mdr m Femdm EDUCATION (&,$n with baccalaureate training and include postdoctoral) INSTITUTION AN0 LOCATION OEGREE YEAR SCIENTIFIC CONFERRED FIELD State University of New York at Buffalo B.A. 1971 Mathematics & Chemistr University of California, Berkeley Ph.D. 1975 Chemistry Institute in Quantum Chemistry, Solid State Physics & Quantum Biology, Uppsa 1 a, Sweden Summer 1973 HONORS Phi Beta Kappa, Pi Mu Epsilon, Alpha Lambda Delta Graduated Magna Cum Laude with Highest Distinction; Allied Chemical Scholar, 1971; Award of American Institute of Chemists for Scholastic Achievement. MAJOR RESEARCH INTEREST ROLE IN PROPOSED PROJECT Application of Computers in Chemistry Direct Cl3 NMR with attention to the structural nature of the problem RESEARCH SUPPORT fsi~ htnrctimd N/A RESEARCH ANDEOR PROFESSIONAL EXPERIENCE &.wrti~ withpr#8ntporition,~andexpetionwrdWant toarea ofpro/bct Listall or mat rupnsantwtivopubliwtionr Do not ucmd 34~478s for wch individcul.) Stanford University 1976 - Computer Science Department, Stanford, Calif. IBM, San Jose Research Division, San Jose, Calif. 1975 University of California, Berkeley, Calif. 1971-197s Thesis: The Excited Electronic States of HCN and HNC; a New Method to Obtain Wave Functions of SCF Quality Configuration Interaction Wave Functions to Obtain Optimized Minimum Basis Set Potential Surfaces State University of New York at Buffalo, Buffalo, N.Y. NIH 398 (f ORYERLY PltS 398) Rev. 1173 I- --_ t ". 8. co"gRNMENT PRINTING OFFlCE : 1074 584-2%3/3034 GRETCHEN M. SCHWENZER Bi bl iography "Photochemical Substitution Reactions of Substituted Group VI Metal Carbonyl s ,`I G. Schwenzer, M.Y. Darensbourg, and D.J. Darensbourg, Inorganic Chemistry_, 11, 1967 (1972). "Photochemical Substitution Reactions of Substituted Group VI Metal Carbonyl s ,I' G. Schwenzer, D.J. Darensbourg, M.Y. Darensbourg, ACS Meeting, New York, Aug. (1972). "Use of nonrelativistic wavefunctions for the prediction of properties of molecules containing atoms of high Z. PbO as a test case," Gretchen M. Schwenzer, Dean H. Liskow, and Henry F. Schaefer, The Journal of Chemical - Physics, Vol. 58, No. 8, 15 April 1973. "Geometries of the excited electronic states of HCN," Gretchen M. Schwenzer, Stephen V. O'Neil, and Henry F. Schaefer, The Journal of Chemical Physics, Vol. 60, No. 7, 1 April 1974. - "The Hypervalent Molecules Sulfurane (SH4) and Persulfurane (SH6) ,`I Gretchen M. Schwenzer and Henry F. Schaefer, The Journal of the American Chemical Society, 97, 1393 (1975). -- "Excited Electronic States of HNC, Hydrogen Isocyanide," Gretchen M. Schwenzer, Henry F. Schaefer, and Charles F. Bender, The Journal of Chemical Physics, 63, 569 (1975). - "Confirmation of the Discrepancy Between Theory and Experiment for the B 'AlI state of HCN," Gretchen M. Schwenzer, Henry F. Schaefer and Charles F. Bender, Chemical Physics Letters, Vol. 36, No. 2, 179 (1975). "Documentation of ALCHEMY", Gretchen M. Schwenzer, IBM Report. SECTION II -PRIVILEGED COMMUNICATION BIOGRAPHICAL SKETCH (Give the folIowIng Informetion for o llprofassrsionel personnel &ted on pege 3, beginnlq m'th the Princlpel Invati@or. (he continuation psoar end follow the mrne #enoral formet for tih penon) MAME ITITLE ' ~BIRTHDATE IMa. Dw. W HAROLD D. BROWN Research Associate 7-l 2-34 PLACE OF BIRTH fCiry, State, CounWyj PRESENT NATIONALITY f/f non-U.S cltlzen, indicata kind of visa and expiretion drtd SEX South Bend, Indiana, U.S.A. U.S. citizen EDUCATION (Be& with baccelaureete treining end include pattd*torall 43 Ml310 0 Female INSTITUTION AND LOCATION I DEGREE YEAR SCIENTIFIC CONFERRED FIELD University of Notre Dame Ohio State University HONORS M.Sc. Ph.D. 1963 Mathematics 1966 Mathematics MAJOR RESEARCH INTEREST ROLE IN PROPOSED PROJECT Research Associate RESEARCH SUPPORT &m instructionsl Pending, "Computer-Assisted Molecular Structure Elucidation", 12-month grant. Proposed Amount: $42,733 Period: 11/l/75-10/31/77 Source : National Science Foundation RESEARCH ANDDR PROFESSIONAL EXPERIENCE (Startiw withprasntposition,f&&&&endexpetienwr~evant toeree ofprobf Listall or mat reprsrentativepubliwtionr Do not exceed 3 peges for och individual.) 1971-72 Associate Professor, Computer Science Department, Stanford University 1973- 1973- Research Associate, Medical School, Stanford University 1963-7s Instructor/Assistant Professor, Assistant Chairman/Associate Professor, Mathematics, The Ohio State University Winter Visiting Professor, Mathematics, Rhine. Westf. Tech. Hoch., Aschen 1971, 73 and 75 1964-70 Director/Associate Director, National Science Foundation SSTP 1967-68 Visiting Member, Courant Institute of Mathematical Sciences, New York University 1 g6o- 63 Assistant to the Chairman, Mathematics, University of Notre Dame N IH 398 (FORMERLY PM 398) Rev. 1173 t ". 8. C.O"ElWMMT PRINTING OP'FiCE : 1974 %X-253/3334 Publications: Near Algebras, Tll. J. Math. 12(196R), p. 215. nistrihrltor Theory in Near Algebras, Comn. Pure Appl. ?la t . X(X1(1968), p. 535. An Algorithm for the Determination of Space Croups, Math. Comp. 23(1969), p. 499. Some Empirical Observations on Primitive Roots (with II.. Zassenhaus), J. ?'umber Theory 3(1971), p. 306. A Generalization of Farey Sequences (with K. Mahler), J. p!umbcr Theory 3(1971), p. 364. Basic Computations for Orders, Stanford CS Report STAN-CS-72-298. An Application of Zasscnhaus' ITnit Theorem, Acta Arith. xX(1972), p. 154. Integral Groups I: The Reducible Case (with J. ?IeIlbuser and H. Zasscnhaus), Kumer. Math. 19(1972), p. 386. Tntegral Groups II: The Irreducible Case (with J. Neubuser and H. Zassenhaus), Nuner. Math. 20(1972), p= 220 Integral Groups III: Normalizers (with .J. Neuhuser and H. Zasscnhaus), Math. Comp. 27(1973), p. 167. Constructive Graph Labeling via Double Cosets (with 1,. Hjelmeland and I Masinter) Discrete Math. 7(1973), p. 1; and Stanford &AN-U-72-3;& CS Report An Algorithm for the Construction of the-Graphs of Organic Molecules (with L. Masinter), Discrete Math. 8(1974), p. 227; and Stanford CS Report STAN-CS-73-261. The Crystallographic Groups of 4-dimensional Space (with J. Neubuser, H. Wondratschek and H . Zassenhaus), Wiley Interscience (in preparation). Molecular Structure Elucidation III: Fragment Emhedding, sot. Tndustrial and Applied Math. J. on Computing (submitted), and Stanford CS Report STAN-CS-74-469. Applications of Artificial Intelligence for Chemical Inference XVII. Computer Generation of Vertex Graphs and Ring Systems (with R. Carhart, N. Sridharan and D. Smith), J. Chem. Tnf. Camp. Set. (in press). Applications of Artificial Tntelligence for Chemical Inference XVIII. An Approach to Computer-Assisted Elucidation of Molecular Structure (with R. Carhart and D. Smith), JACS (in press). Table of Contents Table of Contents Section Subsection Page 1 . Introduction . . . . . . . . 1.1 Objectives . . . . . . . . 1.2 Background and Rationale . . . . . 1.3 Existing Capabilities . . . . . . 1.4 Relationship to Mass Spectrometry and AIM-SUMEX Resources . . . . . . 2. Specific Aims . . . . . . . . 2.1 Add More llIntelligence" to Existing Programs . . . . . . . . 2.2 Develop New Computer Programs that Assist in Biomolecular Structure Elucidation 2.3 Develop New Programs that Aid in Rule Formation . . . . . . . . . 2.4 Apply the Structure Elucidation Programs and GC/HRMS . . . . . . . . . 2.5 Increase the Availability of the Structure Elucidation Techniques . . 2.6 Maintain and Improve the GC/HRMS System 3. Methods . . . . . . . . . 3.1 Extra Intelligence in Existing Programs . 3.2 New Programs for Structure Elucidation 3.3 New Programs for Theory Formation . . 3.4 Applications . . . . . . . . 3.5 Increased Availability . . . . . i . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 11 11 12 13 14 14 14 15 15 18 30 35 42 Table of Contents 3.6 The GC/HRMS Resource ......... 46 4. BIBLIOGRAPHY ........... 48 5. Appendix I ........... 56 6. Appendix II ........... 61 ii