From thomas_w: at :btm2x2.mat.uni-bayreuth.de Fri Aug 18 03:18:51 1995 Received: from btr0x1.hrz.uni-bayreuth.de for thomas_w;at;btm2x2.mat.uni-bayreuth.de by www.ccl.net (8.6.10/950810.1506) id DAA16108; Fri, 18 Aug 1995 03:03:03 -0400 Received: from btm2x2.mat.uni-bayreuth.de by btr0x1.hrz.uni-bayreuth.de (4.1/btr0x1 (UBTGW/btr0x1-2.4.7)) id AA08858; Fri, 18 Aug 95 09:02:43 +0200 Received: by btm2x2.mat.uni-bayreuth.de (4.1/SMI-4.1) id AA00142; Fri, 18 Aug 95 09:00:43 +0200 Date: Fri, 18 Aug 95 09:00:43 +0200 From: thomas_w /at\btm2x2.mat.uni-bayreuth.de (Thomas Wieland) Message-Id: <9508180700.AA00142- at -btm2x2.mat.uni-bayreuth.de> To: chemistry[ AT ]www.ccl.net Subject: Summary: Topological indices Dear Netters, here is my summary for my recent question on software for topological indices. It took some time because two weeks ago the mainboard of my computer was stolen such that I didn't have access tothe data on my hard disk (meanwhile I got a new one). Furthermore I have to admit that I hadn't remembered that the same question had been posted this spring (by "Richard Bone" on 22 May 1995 14:45:43 - look for it in CCL archive). The inquiries I received show, however, that the need for information on this topic is not fulfilled yet. Thanks to all scientists who answered. My special thank are due to Dr. S. Basak of Resource Institute, Dulluth, MN, who even sent me a pile of (p)reprints of his works with a lot of valuable information and useful references. It turned out that there is excellent software available - but not public domain. Some simple connectivity or distance indices are certainly not hard to implement and can be looked up in a large number of publications. But some more efforts are needed to program more complex indices. Best regards, Th. Wieland Thomas Wieland +---------------+ Dipl. Math. |+---- +----+| Lehrstuhl II f. Mathematik |\ \ | || Universitaet Bayreuth | \ \ | || | \ \ | || 95440 Bayreuth | \ \\ || Germany | \ \\ || Tel. +49 (921) 553386 | \ \\ || Fax +49 (921) 553385 | \-------|| +---------------+ ------------------------------------------------------------------------------ Original question was: >Dear Colleagues, > >I am looking for some simple programs (preferably public-domain, >best with sources) that are able to compute topological indices >of molecular graphs, no matter which (Wiener-Index, Randic-Index >etc.) > >I would gratefully appreciate any hints to ftp-sites where such software >can be found. I tried some WWW-search machines but my key words "topological >index" didn't suffice. > ------------------------------------------------------------------------------ From: Lipkowitz A great list of programs for computational chemistry is in each Appendix of Reviews in Computational Chemistry, VCH Publishers Inc. The list is prepared by Don Boyd and I'm sure has what you're looking for. Kenny ------------------------------------------------------------------------------ From: "Dr. Subhash Basak" Thank you for your inquiry. We have two programs, POLLY and APPROBE which are currently being used by companies like Upjohn, Glaxo, Government agencies like U S Environmental Protection Agency, National Institutes of Health, US Army for molecular design and QSAR analysis pertaining to health and environment. I am sending you info about POLLY AND APPROBE below. I am also mailing you a collection of my papers in the area of development of topological indices and their applications in QSAR and quantifications of molecular similarity as well as applications of similarity in estimating properties of molecules. The POLLY software is copyright of the University of Minnesota. Licensing/ ordering information regarding POLLY can be obtained from Bob Hicks of the Office of Research and Technology Transfer Administration (ORTTA) of the U of Minnesota. Bob can be reached at: bob#* at *#ortta.umn.edu. The price of the software is $2,000.00 (two thousand dollars only) per licensed site. Mr. Hicks can give you more details about the licensing aspects. POLLY v. 2.3 S.C. Basak Natural Resources Research Institute University of Minnesota Duluth, Minnesota 55811 USA D.K. Harriss V.R. Magnuson Department of Chemistry University of Minnesota Duluth, Minnesota 55812 USA !Copyright (C) 1986, 1988 Regents of the University of Minnesota. All Rights Reserved. I. Introduction POLLY is a tested and documented computer program which calculates the values of 98 topological (graph theoretic, connectivity and complexity type) indices for molecules containing up to 120 atoms composed of the following atom types: carbon, nitrogen, oxygen, chlorine, bromine, sulfur, fluorine, phosphorous, iodine, boron and hydrogen. These indices include the Zagreg group indices1 , Wiener index2, Randic's connectivity index3, higher order connectivity indices and valence connectivity indices of different types4, bonding connectivity indices5, information theoretic indices based on distance matrix6, indices of neighborhood symmetry7,8, information theoretic indices of degree complexity, distance complexity and vertex complexity9, information theoretic indices on graph orbits10, and paths of different lengths. Topological indices have been successfully used in the quantification of molecular similarity5, 11-15, structure-property correlations2-4,16-19, and prediction of biomedicinal and toxic properties of different classes of molecules4,7,8,20. The program is structured to accept molecular descriptions in the form of SMILES notation but is easily adapted to other, user oriented, forms of input such as MOLFILE. The output consists of values of the 98 indices for each molecule. POLLY is programmed in ANSI C and has been tested on UNIX and MSDOS platforms. POLLY is provided in source code form only on UNIX platforms, both source and executable for the MSDOS platform. II. Running POLLY POLLY may be run in either interactive (input from the keyboard) or batch (input from a file) modes. To enter input from the keyboard, just type polly at the operating system prompt: Prompt> polly POLLY will then respond with a SMILES: prompt. At this point, type in the SMILES string to specify the compound. The indices, or an error message if an invalid SMILES string, will be output to the console. A sequence number is output as well. This number is just how many compounds POLLY has processed during the current session. The usage of POLLY in batch mode has the following format: Prompt> polly input_name Here input_name is the name of the file with molecule identifiers and SMILES strings (See Sec III for descriptions). The default extension for this file is ".smi" and may be dropped from the command line. If any other extension is used it must be explicitly stated. By default, POLLY will write indices to a file with the same base name as the input file, appending the extension .mci and error messages to a file with the extension .err. For example, if a user runs POLLY with the following command line: polly test.smi indices will be written to test.mci and error messages will be written to test.err. You my override these defaults by specifying the output and error file names on the command line. III. Input A. Format For batch mode, POLLY requires an identifier followed by one or more spaces, and a SMILES21 string (described below). The sequence number and SMILES string must occur on one line. The identifier may be composed of any ASCII character, excluding white space characters and is limited to 80 characters in length. B. SMILES string POLLY uses the SMILES (Simplified Molecular Identification and Line Entry System) method for specifying topological structure of a compound. The structure represented by a SMILES string should, under most circumstances, be hydrogen suppressed. The SMILES interpreter within POLLY will determine the location of hydrogens implicitly by the normal valence of the atoms to which they would be connected. 1. Atom representation Each atom is represented by its atomic symbol. For single letter symbols, use lower case letters to represent aromatic atoms, upper case letters to represent aliphatic atoms. Double letter symbols are represented be an uppercase first letter, lowercase second letter. If you must indicate aromaticity of an atom with a double letter symbol, the symbol should be followed by an "!". Double letter symbols can have ambiguous interpretation. For example, the symbol for silicon, Si, could be interpreted as aliphatic sulfur bonded to aromatic iodine. Any double letter symbol that could have ambiguous interpretation should be enclosed in square brackets "[]". Silicon would then be represented by [Si]. If the double letter symbol would not have ambiguous interpretation, the brackets are not required (e.g. bromine is Br, not [Br]). Examples: Chlorine Cl or [Cl] Silicon [Si] Aliphatic carbon C Aromatic carbon c 2. Bonds By default, the bond between any two atoms is a single bond (see section III.B.4, aromatic rings for an exception). To override this default, the bond must be explicitly represented. The following bond types are available: Single - Double = Triple # Examples: Ethane CC or C-C Ethene C=C Ethyne C#C 3. Branches When an atom has more than two connecting atoms, the additional connecting chains should be enclosed in parentheses. The chain within a set of parentheses is interpreted as being connected to the atom immediately preceding the left parenthesis. You may nest parentheses. Examples: Carbon tetrachloride ClC(Cl)(Cl)Cl Di-n-butylphosphate O=P(OCCCC)OCCCC or CCCCOP(=O)OCCCC Note in the second SMILES string for Di-n-butylphosphate the double bond to the oxygen is also enclosed within the parentheses. Any bonding information to an atom within parentheses must also be enclosed within the parentheses. 4. Rings To represent a ring as a linear structure, one bond in the ring must be broken. This structure can then be represented as a linear string. To identify where the broken bond occurred, each atom that was involved is labeled with a digit(s). These two atoms comprise a ring-closure pair. The digit is placed following the two atoms that had the bond broken between them. The interpreter may then re-establish the bond in the connection matrix. Two digits may be used to identify ring-closure pairs if they are preceded by the character "%". Therefore, up to 99 (1-99) rings may be labeled. Examples: Cyclohexane C1CCCCC1 1-Methylcyclopentene CC%11=CCCC%11 Aromatic ring: SMILES notation allows atoms in aromatic rings to be represented with lower case atomic symbols. This avoids having to designate conjugated double bonds in aromatic rings, i.e. the default is not a single bond, but the conjugated double bond. Examples: Benzene c1ccccc1 Naphthalene c1cc2ccccc2cc1 5. Atom Qualifiers Placing square brackets around an atom symbol allows you to specify additional information about an atom that can not be implicitly deduced from the connection table. This would include formal charges or hydrogens about an aromatic nitrogen. Examples: Pyrrole c1cccc[nH]1 Tetramethylammonium C[N+](C)(C)C 6. Restrictions a. POLLY utilizes only a subset of all possible atoms, those that allow the representation of most organic compounds. b. The maximum SMILES string length is 120. c. The maximum number of atoms for any compound is 120. d. Only compounds that can be represented by a connected graph are allowed. e. Hydrogens should not be included in the SMILES string except as qualifiers. IV. Output Appendix 1 describes the indices output by POLLY. The order the indices are listed corresponds to the order in which they are output by POLLY. Appendix 2 lists the parameters output on a record by record basis. V. References 1. I. Gutman, B. Ruscic, N. Trinajstic and C. F. Wilcox, Jr., Graph theory and molecular orbitals, Part XII. Acyclic polyenes. J. Chem. Phys., 62, 3339-3405 (1975). 2. H. Wiener, Structural determination of paraffin boiling points, J. Amer. Chem. Soc., 69, 17-20 (1947). 3. M. Randic', On characterization of molecular branching, J. Am. Chem. Soc. 97, 6609-6615 (1975). 4. L.B. Kier and L.H. Hall, Molecular Connectivity in Structure-Activity Analysis (Research Studies Press, Letchworth, Hertfordshire, U.K., 1986). 5. S.C. Basak, V.R. Magnuson, G.J. Niemi and R.R. Regal, Determining structural similarity of chemicals using graph-theoretic indices, Discrete Applied Mathematics, 19, 17 (1988); Special Volume: Applications of Graph Theory in Chemistry and Physics, J.W. Kennedy and L.V. Quintas (eds.). 6. D. Bonchev and N. Trinajstic, Information theory, distance matrix and molecular branching, J. Chem. Phys., 67, 4517-4533 (1977). 7. A.B. Roy, S.C. Basak, D.K. Harriss and V.R. Magnuson, Neighborhood Complexities and Symmetry of Chemical graphs and their biological applications, in Mathematical Modelling in Science and Technology, X.J.R. Avula, R.E. Kalman, A.I. Lipais and E.Y. Rodin (Eds.), p. 745, Pergamon Press, 1984. 8. S.C. Basak, Use of molecular complexity indices in predictive pharmacology and toxicology: a QSAR approach, Med. Sci. Res., 15, 605 (1987). 9. C. Raychaudhury, S.K. Ray, J.J. Ghosh, A.B. Roy and S.C. Basak, Discrimination of isomeric structures using information-theoretic topological indices, J. Comput. Chem., 5, 581 (1984). 10. N. Rashevsky, Life, information theory and topology, Bull. Math. Biophys., 17, 229-235 (1955). 11. M. Randic', in: Computer Based Methods of Molecular Similarity, ed. G.M. Maggiora (John Wiley, in press, 1989). 12. S.C. Basak, V.R. Magnuson, G.J. Niemi, R.R. Regal and G.D. Veith, Topological indices: their nature, mutual relatedness, and applications, Mathematical Modelling, 8, 300 (1987). 13. M. Johnson, S.C. Basak and G. Maggiora, A characterization of molecular similarity methods for property prediction, Mathematical and Computer Modelling, II, 630 (1988). 14. M. Lajiness, Molecular Similarity Based Methods for Selecting compounds for Screening, in: Computational Chemical Graph Theory, Ed. D. H. Rouvray, Nova, New York. pp. 299-316 (199). 15. S.C. Basak, S. Bertelsen and G.D. Grunwald, Application of graph theoretic parameters in quantifying molecular similarity and structure-activity relationships, presented at the Fifth International Conference on Mathematical Chemistry (1993). 16. S.C. Basak and G.D. Grunwald, Use of graph invariants, volume and total surface area in predicting boiling point of alkanes, Mathematical Modelling and Scientific Computing, 2, 735-740 (1993). 17. S.C. Basak, G.J. Niemi and G.D. Veith, Optimal characterization of structure for prediction of properties, J. Math. Chem., 4, 185 (1990). 18. Basak, S.C. A Nonempirical Approach to Predicting Molecular Properties using Graph-Theoretic Invariants, in PRACTICAL APPLICATIONS OF QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSAR) IN ENVIRONMENTAL CHEMISTRY AND TOXICOLOGY, eds. W. Karcher and J. Devillers, Kluwer Academic Publishers, (1990). 19. G.J. Niemi, S.C. Basak, G.D. Veith and G. Grunwald, Prediction of octanol- water partition coefficient (Kow) using algorithmically-derived variables, Environmental Toxicology and Chemistry, 11, 893-900 (1992). 20. G.J. Niemi, S.C. Basak and G.D. Veith, A theoretical and computational approach to chemical evaluation based on structure-activity relationships, Procedeedings of the First Conference of the International Society of Environmental Protection, pp 57-68 (1990). 21. E.B. Anderson, G.D. Veith, and D. Weininger, SMILES: A Line notation and computerized interpreter for chemical structures, Environmental Research Brief, U.S. EPA, (1987). ! Appendix 1: The 98 topological indices calculated by POLLY. IWD Information index for the magnitudes of distances between all possible pairs of vertices of a graph IWD Mean information index for the magnitude of distance W Wiener index = half-sum of the off-diagonal elements of the distance matrix of a graph ID Degree complexity HV Graph vertex complexity HD Graph distance complexity IC Information content of the distance matrix partitioned by frequency of occurrences of distance h O Order of neighborhood when ICr reaches its maximum value for the hydrogen-filled graph IORB Information content or complexity of the hydrogen-suppressed graph at its maximum neighborhood of vertices OORB Maximum order of neighborhood of vertices for IORB within the hydrogen- suppressed graph M1 A Zagreb group parameter = sum of square of degree over all vertices M2 A Zagreb group parameter = sum of cross-product of degrees over all neighboring (connected) vertices ICr Mean information content or complexity of a graph based on the rth (r = 0..6) order neighborhood of vertices in a hydrogen-filled graph SICr Structural information content for rth (r = 0..6) order neighborhood of vertices in a hydrogen-filled graph CICr Complementary information content for rth (r = 0..6) order neighborhood of vertices in a hydrogen-filled graph h! Path connectivity index of order h = 0..6 h!C Cluster connectivity index of order h = 3..6 h!Ch Chain connectivity index of order h = 3..6 h!PC Path-cluster connectivity index of order h = 4..6 h!b Bonding path connectivity index of order h = 0..6 h!bC Bonding cluster connectivity index of order h = 3..6 h!bCh Bonding chain connectivity index of order h = 3..6 h!bPC Bonding path-cluster connectivity index of order h = 4..6 h!v Valence path connectivity index of order h = 0..6 h!vC Valence cluster connectivity index of order h = 3..6 h!vCh Valence chain connectivity index of order h = 3..6 h!vPC Valence path-cluster connectivity index of order h = 4..6 Ph Number of paths of length h = 0..10 ! Appendix 2: Format of the POLLY output file Record 1: Chemical id (a80) Record 2: IWD, IWD, W, ID, HV, HD, IC (f11.3, f8.3, i6, 4f8.3) Record 3: O, IORB, OORB, M1, M2 (i6, f8.3, 3i6) Record 4: IC0, IC1, ..., IC6 (7f8.3) Record 5: SIC0, SIC1, ..., SIC6 (7f8.3) Record 6: CIC0, CIC2, ..., CIC6 (7f8.3) Record 7: 0!, 1!, ..., 6! (7f8.3) Record 8: 3!C, 4!C, 5!C, 6!C (24x, 4f8.3) Record 9: 3!Ch, 4!Ch, 5!Ch, 6!Ch (24x, 4f8.3) Record 10: 4!PC, 5!PC, 6!PC (32x, 3f8.3) Record 11: 0!b, 1!b, ..., 6!b (7f8.3) Record 12: 3!bC, 4!bC, 5!bC, 6!bC (24x, 4f8.3) Record 13: 3!bCh, 4!bCh, 5!bCh, 6!bCh (24x, 4f8.3) Record 14: 4!bPC, 5!bPC, 6!bPC (32x, 3f8.3) Record 15: 0!v, 1!v, ..., 6!v (7f8.3) Record 16: 3!vC, 4!vC, 5!vC, 6!vC (24x, 4f8.3) Record 17: 3!vCh, 4!vCh, 5!vCh, 6!vCh (24x, 4f8.3) Record 18: 4!vPC, 5!vPC, 6!vPC (32x, 3f8.3) Record 19: P0, P1, ..., P10 (11i6) ------------------------------------------------------------------------ From: lnl # - at - # novo.dk (Leif Norskov) Molconn-X is *THE* program for calculating topological indices. ( - sometimes referred to as Kier and Hall indices). It is available for $ 295 for academic users from Lowell H. Hall Hall Associates Consulting 2 Davis Street Quincy, MA 02170, U.S.A. Tel. (617) 773-4833 Lowell does not seem to have an email address, but he certainly does put some nice stamps on his ordinary mail :-) ------------------------------------------------------------------------ From: "Igor Baskin" In connection with your inquiry about topological indexes, I enclose a small extraction from the description of the EMMA package. "EMMA" ("EFFECTIVE MODELLING OF MOLECULAR ACTIVITY") - THE SOFTWARE FOR THE PREDICTION OF PROPERTIES/BIOLOGICAL ACTIVITIES OF ORGANIC COMPOUNDS ON THE BASIS OF REGRESSION ANALYSIS ... For each structure in a training set EMMA allows to compute from hundreds to thousands of descriptors. The set of descriptors includes topological indices (various connectivity indices, Balaban index J, Wiener and extended Wiener, Hosoya, Merrifield-Simmons, Gutman and some other indices), informational indices, the indices which are the functions of charge distribution in molecules, the indices based on atomic electronegativities and those based on inductive parameters, steric indices, various local indices and, what is important, the substructural descriptors which are equal to the number of chaines (1- to 9-atomic), the number of cycles (3- to 6-membered) and the number of branched fragments (4-, 5-, and 6-atomic), the atoms in substructures being classified taking into account the number of hydrogens at them, bond types and formal charge. EMMA can manage 2000 descriptors computed and construct the regression equations including only a few "best" descriptors. A user can easily add his own descriptor programs or can input the additional descriptor values manually. ... Developers: Professor N.S.Zefirov, Department of Chemistry, Moscow State University, Moscow, 119899, Russia. Fax: (095) 939-0290, phone (095) 939-1620 Dr. D.V.Sukhachev, Dr. I.I.Baskin, Dr. V.A.Palyulin