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 ...
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...
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...
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.
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 .
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 ...
... 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. ...
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 ...
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...
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...
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.
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 .
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 ...
... 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. ...
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