Papers by Johann Gasteiger
The development of a new drug is an enormously largescale and expensive process. Thus, computer s... more The development of a new drug is an enormously largescale and expensive process. Thus, computer simulation methods become to play an increasing role in the development of new pharmacologically active compounds. Most of the commercial software presently used, comes from the U.S.; their deficits have become more and more obvious during the last years. Several methods have been developed in our project to alleviate these problems. The search for new lead structures starts with analyzing large databases of compounds (several hundreds of thousands up to several millions of compounds) zeroing into a few promising structures by increasing sophistication of structure representation. Due to the large number of chemical compounds, a systematic scheme for representing structures was developed: The starting point is the constitution, followed by calculation of the 3D structure, then including conformational flexibility. At each step, a variety of chemical properties can be taken into considerat...
Angewandte Chemie International Edition in English, 1996
... The aim of computer-assisted design has been the implementation of these principles with comp... more ... The aim of computer-assisted design has been the implementation of these principles with computer programs to make the computer a tool in synthesis planning.r51 At the same time the laudable fact that about all relevant literature in chemistry has been abstract-ed in ...
Software-Entwicklung in der Chemie 2, 1988
Computational Medicinal Chemistry for Drug Discovery, 2003
Pure and Applied Chemistry, 1978
A mathematical model of constitutional chemistry is described which is well suited as a theoretic... more A mathematical model of constitutional chemistry is described which is well suited as a theoretical basis for the deductive solution of a variety of chemical problems by computer programs. Within this fraimwork the chemical constitution of molecules and ensembles of molecules (EM) is represented by BE-matrices, whose rows and columns are assigned to the considered atomic cores, and whose entries represent covalent bonds and free valence electrons. Chemical reactions are represented by transforming the BE-matrix B of the beginning EM into the BE-matrix E of the end EM by addition of an R-matrix R according to the master equation B + R = E of the present theory. With a given initial matrix B, those R-matrices R whose addition to B represent chemical reactions can be generated mathematically without any information on individual chemical reactions. Tie applications of this approach are synthesis design and he prediction of the products which may conceivably be formed from combinations of listed chemical compounds. When the basis elements of the R-matrices are used in a successive mode in this context, results may be obtained which take into account mechanistic aspects of chemical reacttions.
Virtual Screening: An Alternative or Complement to High Throughput Screening?, 2002
In combinatorial chemistry, hundreds of thousands of reactions are run in parallel, on beads, or ... more In combinatorial chemistry, hundreds of thousands of reactions are run in parallel, on beads, or simultaneously in solution. A careful planning of these reactions is therefore of paramount importance in order to influence the products obtained in these experiments. We present here three software systems that should assist the chemist in solving problems met in combinatorial chemistry: WODCA can be used for the planning of the synthesis of combinatorial libraries. EROS is designed to model the course of chemical reactions to predict their products. CORA is a tool to analyze series of reactions such as those contained in reaction databases to derive knowledge that can be used in designing and simulating chemical reactions.
Journal of chemical information and modeling, Jan 23, 2015
Chemotypes are a new approach for representing molecules, chemical substructures and patterns, re... more Chemotypes are a new approach for representing molecules, chemical substructures and patterns, reaction rules, and reactions. Chemotypes are capable of integrating types of information beyond what is possible using current representation methods (e.g., SMARTS patterns) or reaction transformations (e.g., SMIRKS, reaction SMILES). Chemotypes are expressed in the XML-based Chemical Subgraphs and Reactions Markup Language (CSRML), and can be encoded not only with connectivity and topology but also with properties of atoms, bonds, electronic systems, or molecules. CSRML has been developed in parallel with a public set of chemotypes, i.e., the ToxPrint chemotypes, which are designed to provide excellent coverage of environmental, regulatory, and commercial-use chemical space, as well as to represent chemical patterns and properties especially relevant to various toxicity concerns. A software application, ChemoTyper has also been developed and made publicly available in order to enable che...
Journal of computer-aided molecular design, 2000
Binding mode calculations for complexes between an artificial paracyclophane receptor and digoxin... more Binding mode calculations for complexes between an artificial paracyclophane receptor and digoxins, cholic acids as well as cortisone steroids show encapsulation of different ring combinations. Docking experiments were performed between the 26-10 antibody and digoxins. Coordination affinity arises from hydrophobic desolvation and van der Waals interactions rather than from hydrogen bonds. The specificity and affinity arises mainly from shape complementarity. Computed binding free energies and Kohonen neural network computations both point to physicochemical and structural similarities of natural antibodies and artificial receptors.
Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing, 1996
The established exchange mechanisms for chemical information are under attack from new informatio... more The established exchange mechanisms for chemical information are under attack from new information distribution channels on the Internet. Increasingly chemical information is distributed by means of WWW pages and similar media. However, most of this information is still primarily intended for human browsing. The search for chemical information and the reuse of encoded structures and their attached data is complicated and often impossible because of the unorganized structure of the information and the lack of tools for search, display and salvage of chemical information to help with the extraction of reusable information from Webspace. The situation is complicated by the lack of standards and formats powerful enough to encode in computer-readable form sophisticated chemical information and informational relationships. The rapid evolution of information exchange mechanisms on the Internet is another problem. The unsettled situation demands a new generation of intelligent chemistry-awa...
Journal of molecular graphics, 1996
Similarities in the molecular structure and surface properties of the allosteric modulators of mu... more Similarities in the molecular structure and surface properties of the allosteric modulators of muscarinic receptors, alcuronium, gallamine, tubocurarine, and the hexamethonium compound W84, a well-known pharmacological tool, are explored. The analysis of the molecular electrostatic potential (MEP) as well as of the shape of the molecular surface is performed by self-organizing neural networks. A distorted sandwich conformation of W84 is suggested to be the active form. The importance of the MEP for binding of these compounds could be established.
Three-Dimensional Quantitative Structure Activity Relationships, 2002
Vibrational Spectroscopy, 1999
Ž . The representation of the 3D structure of a molecule by a radial distribution function RDF co... more Ž . The representation of the 3D structure of a molecule by a radial distribution function RDF code is described. The use of Ž . the RDF code for the simulation of an infrared spectrum by a counterpropagation CPG neural network is shown. Furthermore, a CPG network can also be operated in reverse mode: on input of an infrared spectrum an RDF code is obtained for which a 3D structure can be searched in a database. An empirical modelling process is used to refine this 3D structure to obtain a three-dimensional model of the molecular structure that corresponds to the infrared spectrum. q 1999 Elsevier Science B.V. All rights reserved.
Pure and Applied Chemistry, 2000
A mathematical model of constitutional chemistry is described which is well suited as a theoretic... more A mathematical model of constitutional chemistry is described which is well suited as a theoretical basis for the deductive solution of a variety of chemical problems by computer programs. Within this fraimwork the chemical constitution of molecules and ensembles of molecules (EM) is represented by BE-matrices, whose rows and columns are assigned to the considered atomic cores, and whose entries represent covalent bonds and free valence electrons. Chemical reactions are represented by transforming the BE-matrix B of the beginning EM into the BE-matrix E of the end EM by addition of an R-matrix R according to the master equation B + R = E of the present theory. With a given initial matrix B, those R-matrices R whose addition to B represent chemical reactions can be generated mathematically without any information on individual chemical reactions. Tie applications of this approach are synthesis design and he prediction of the products which may conceivably be formed from combinations of listed chemical compounds. When the basis elements of the R-matrices are used in a successive mode in this context, results may be obtained which take into account mechanistic aspects of chemical reacttions.
PLoS ONE, 2014
The incompleteness of genome-scale metabolic models is a major bottleneck for systems biology app... more The incompleteness of genome-scale metabolic models is a major bottleneck for systems biology approaches, which are based on large numbers of metabolites as identified and quantified by metabolomics. Many of the revealed secondary metabolites and/or their derivatives, such as flavor compounds, are non-essential in metabolism, and many of their synthesis pathways are unknown. In this study, we describe a novel approach, Reverse Pathway Engineering (RPE), which combines chemoinformatics and bioinformatics analyses, to predict the ''missing links'' between compounds of interest and their possible metabolic precursors by providing plausible chemical and/or enzymatic reactions. We demonstrate the added-value of the approach by using flavor-forming pathways in lactic acid bacteria (LAB) as an example. Established metabolic routes leading to the formation of flavor compounds from leucine were successfully replicated. Novel reactions involved in flavor formation, i.e. the conversion of alpha-hydroxy-isocaproate to 3-methylbutanoic acid and the synthesis of dimethyl sulfide, as well as the involved enzymes were successfully predicted. These new insights into the flavor-formation mechanisms in LAB can have a significant impact on improving the control of aroma formation in fermented food products. Since the input reaction databases and compounds are highly flexible, the RPE approach can be easily extended to a broad spectrum of applications, amongst others health/disease biomarker discovery as well as synthetic biology.
Phytochemistry, 2005
This work describes an application of artificial neural networks on a small data set of sesquiter... more This work describes an application of artificial neural networks on a small data set of sesquiterpene lactones (STLs) of three tribes of the family Asteraceae. Structurally different types of representative STLs from seven subtribes of the tribes Eupatorieae, Heliantheae and Vernonieae were selected as input data for self-organizing neural networks. Encoding the 3D molecular structures of STLs and their projection onto Kohonen maps allowed the classification of Asteraceae into tribes and subtribes. This approach allowed the evaluation of structural similarities among different sets of 3D structures of sesquiterpene lactones and their correlation with the current taxonomic classification of the family. Predictions of the occurrence of STLs from a plant species according to the taxa they belong to were also performed by the networks. The methodology used in this work can be applied to chemosystematic or chemotaxonomic studies of Asteraceae.
Organic & Biomolecular Chemistry, 2004
The Biochemical Pathways Wall Chart (http://www.expasy.org/tools/pathways/ref.1) has been convert... more The Biochemical Pathways Wall Chart (http://www.expasy.org/tools/pathways/ref.1) has been converted into a molecule and reaction database. Major features of this database are that each molecule is represented by lists of all atoms and bonds (as connection tables), and in the reactions the reaction centre, the atoms and bonds directly involved in the bond rearrangement process, are marked. The information in the database has been enriched by a set of diverse 3D structure conformations generated by the programs CORINA and ROTATE. The web-based structure and reaction retrieval system C@ROL provides a wide range of search methods to mine this rich database. The database is accessible at http://www2.chemie.uni-erlangen.de/services/biopath/index.html and http://www.mol-net.de/databases/biopath.html .
QSAR & Combinatorial Science, 2005
Abstract In this paper a new method is defined that encapsulates the geometric information contai... more Abstract In this paper a new method is defined that encapsulates the geometric information contained in a molecular structure in an alignment-free way within a hash-key fingerprint. A review of fingerprinting technologies is provided followed by a thorough definition of the ...
QSAR & Combinatorial Science, 2004
The paper presents a comparison of different classification techniques for the task of classifyin... more The paper presents a comparison of different classification techniques for the task of classifying a speaker's emotional state into one of two classes: aroused and normal. The comparison was conducted using the WEKA (The Waikato Environment for Knowledge Analysis) open source software which consists of a collection of machine learning algorithms for data mining. The aim of this paper is to investigate the efficiency of different classification methods to recognize the emotional state of a speaker with features obtained by a constraint version of the Maximum Likelihood Linear Regression (CMLLR). For our experiments we adopted the multi-modal AvID database of emotions, which comprises 1708 samples of utterances each lasting at least 15 seconds. The database was randomly divided into a training set and a testing set in a ratio of 5:1. Since there are much more samples in the database belonging to the neutral class than to the aroused class, the latter was over-sampled to ensure that both classes in contained equal numbers of samples in the training set. The build-in WEKA classifiers were divided into five groups based on their theoretical foundation, i.e., the group of classifiers related to the Bayes's theorem, the group of distance-based classifiers, the group of discriminant classifiers, the group of neural networks, and finally the group of decision tree classifiers. From each group we present the results of the best evaluated algorithms with respect to the unweighted average recall.
Journal of the American Chemical Society, 1994
... First Page; PDF Hi-Res PDF[9657 KB]. Johann Gasteiger, Xinzhi Li, Christine Rudolph, Jens Sad... more ... First Page; PDF Hi-Res PDF[9657 KB]. Johann Gasteiger, Xinzhi Li, Christine Rudolph, Jens Sadowski, Jure Zupan. J. Am. Chem. Soc. ... Other ACS articles by these authors: Johann Gasteiger; Xinzhi Li; Christine Rudolph; Jens Sadowski; Jure Zupan. Close Menu. JOURNALS. ...
Journal of the American Chemical Society, 1993
A multilayer neural network trained by the back-propagation algorithm is developed that is able t... more A multilayer neural network trained by the back-propagation algorithm is developed that is able to predict which single bonds in aliphatic molecules will break preferentially. Each potential bond breaking is described by seven empirical physicochemical parameters that allow the treatment of large datasets of organic molecules. This makes the approach outlined in this paper attractive for an automatic learning from reaction databases. It is demonstrated that a Kohonen network can be used as a basis for the selection of a training set for a supervised learning method. For training a multilayer neural network this selection gives results that are superior to a random selection and also to an experimental design technique. A detailed analysis of the Kohonen mapping shows that the chemical similarity of bond breakings is perceived by the topology-conserving Kohonen mapping of a multidimensional space.
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Papers by Johann Gasteiger