Substructure mining using elaborate chemical representation

Substructure mining algorithms are important drug discovery tools since they can find substructures that affect physicochemical and biological properties. Current methods, however, only consider a part of all chemical information that is present within a data set of compounds. Therefore, the overall aim of our study was to enable more exhaustive data mining by designing methods that detect all substructures of any size, shape, and level of chemical detail. A means of chemical representation was developed that uses atomic hierarchies, thus enabling substructure mining to consider general and/or highly specific features. As a proof-of-concept, the efficient, multipurpose graph mining system Gaston learned substructures of any size and shape from a mutagenicity data set that was represented in this manner. From these substructures, we extracted a set of only six nonredundant, discriminative substructures that represent relevant biochemical knowledge. Our results demonstrate the individual and synergistic importance of elaborate chemical representation and mining for nonlinear substructures. We conclude that the combination of elaborate chemical representation and Gaston provides an excellent method for 2D substructure mining as this recipe systematically explores all substructures in different levels of chemical detail.     

Similarity measures for sets of strings and application in chemical classification

This paper introduces new ideas for quantification of the similarity between chemical compounds. The method adopted makes use of similarity measures derived through comparison of two strings. The derived data on the similarity are then analyzed and applied in the identification of clusters in which the entities are more homogeneous and similar than those outside a cluster.     

Similarity approach to chemical reactivity. Torquoselectivity in pericyclic reactions

The recently proposed topological similarity index was applied to the elucidation of the interesting phenomenon of pericyclic reactivity, the so-called torquoselectivity. It has been shown that the similarity approach is indeed able to provide a simple and consistent explanation of this phenomenon even in nontrivial cases of counter-intuitive contrasteric control.     

Design and development of chemical ontologies for reaction representation

This paper describes the development of chemical ontologies applied to the representation of organic chemical reactions. The ontologies are built using the methodology known as methontology. The hierarchically structured set of terms describing the subdomains, namely, organic reactions, organic compounds, and reagents, are constructed into individual ontologies. The ontologies consist of about 200 concepts and around 125 individuals. A set of binary relations is defined in order to integrate the ontologies with applications. The ontologies are implemented as an XML application with a set of vocabulary describing the domain knowledge. This paper also features an easy-to-use chemical ontological support system (COSS) intended to represent organic chemical reactions automatically. As a model application, the automatic representation of aliphatic nucleophilic substitution reactions is demonstrated using COSS. The paper also describes a keyword-based search system whose functionality is backed with COSS.     

Design and development of computer-aided chemical systems: representation and balance of inorganic chemical reactions

A model for the tracking of inorganic chemical reactions is proposed. Designed to acquire, process, and solve a great number of inorganic reactions, this model will hopefully contribute to the development of powerful computer-aided chemistry teaching systems for use within or without the environment of a virtual laboratory. Using full representation of an inorganic reaction to allow the extraction of chemical knowledge, incomplete reactions (where species are absent) may be completed by adding the necessary species, and reactions may be solved and balanced. Various types of reaction are classified, and a layer-based model is defined for the solution of different reaction types, establishing the basis for the construction of a system which, based on a wide set of production rules, is capable of solving an incomplete inorganic chemical reaction.     

A representation of chemical transformations by labeled graphs

A transitional labeling of a graphG is an assignment of one of the elements of the set (1, -1, 0) to each vertex and edge ofG so that each edge labeled 0 is incident only with vertices labeled 0, and no edge labeled 1 (respectively, -1) is incident with a vertex labeled -1 (respectively, 1). Chemical transformations can be represented by graphs possessing a transitional labeling. The positive (negative) graph of a transitional labelingt of a graphG is the subgraph ofG consisting of the nonnegative (nonpositive) elements ofG. The linking graph oft is the subgraph consisting of the zero elements ofG. A maximum common subgraph of two given graphsG ₁ andG ₂ is a graphF isomorphic to a common subgraph ofG ₁ andG ₂ such that the sum of the number of vertices and number of edges ofF is maximum. A transitional labelingt of a graphG is a transform if there exists an extensiont oft to a supergraphG of G such that the linking graph oft is a maximum common subgraph of the positive and negative graphs oft. Transforms are used to model chemical reaction pathways. Transforms and related concepts are studied in this paper. A characterization of transforms is also given.Dedicated to Professor Frank Harary on the occasion of his 70th birthday Research supported in part by Office of Naval Research Contract N00014-91-J-1060.     

Similarity clustering of proteins using substantive knowledge and reconstruction of evolutionary gene histories in herpesvirus

The issue of clustering proteins into homologous protein families (HPFs) has attracted considerable attention by researchers. On one side, many databases of protein families have been developed by using popular sequence alignment tools and relatively simple clustering methods followed by extensive manual curation. On the other side, more elaborate clustering approaches have been used, yet with a very limited degree of success. This paper advocates an approach to clustering protein families involving knowledge of the protein functions to adjust the parameter of similarity scale shift. One more source of external information is utilised as we proceed to reconstruct HPF evolutionary histories over an evolutionary tree; the consistency between these histories and information on gene arrangement in the genomes is used to narrow down the choice of the clustering.     

Similarity approach to chemical reactivity. Theoretical justification of the Hammond postulate

The recently proposed similarity index was applied to the quantitative justification of the empirical Hammond postulate for a series of selected pericyclic reactions. In keeping with the expectations of the postulate the transition states were shown to be reactant-like for exothermic and product-like for endothermic reactions.     

Similarity and dissimilarity in posets

The relevance of partially ordered sets (or posets) in a wide diversity of contexts in chemistry is emphasized, and the utility of distance functions (or metrics) on such posets is noted. First a notion of scale similarity is introduced to make comparisons within certain so-called scaled posets, for which there is formulated natural comparators, which in turn lead to associated distance functions. Beyond taking note of several chemically relevant examples of these scaled posets and their consequent associated similarity measures, a second chemically relevant class of so-called shifted posets is similarly developed, with examples. Even further extension of some aspects of the current approach is indicated, and finally the multi-posetic character of chemical periodic law is suggested.     

Similarity searching in files of three-dimensional chemical structures: Representation and searching of molecular electrostatic potentials using field-graphs

This paper reports a method for the identification of those molecules in a database of rigid 3D structures with molecular electrostatic potential (MEP) grids that are most similar to that of a user-defined target molecule. The most important features of an MEP grid are encoded in field-graphs, and a target molecule is matched against a database molecule by a comparison of the corresponding field-graphs. The matching is effected using a maximal common subgraph isomorphism algorithm, which provides an alignment of the target molecule's field- graph with those of each of the database molecules in turn. These alignments are used in the second stage of the search algorithm to calculate the intermolecular MEP similarities. Several different ways of generating field-graphs are evaluated, in terms of the effectiveness of the resulting similarity measures and of the associated computational costs. The most appropriate procedure has been implemented in an operational system that searches a corporate database, containing ca. 173,000 3D structures.     

Solving incomplete inorganic chemical systems through a fuzzy knowledge frame

A model for the completion and balancing of inconsistent inorganic reactions is presented. A series of fuzzy parameters is proposed. These parameters are considered within a knowledge frame representing inorganic reactions via a semantic/functional network and, through the calculation of possibility measures, allow the completion and solution of such reactions by considering new inorganic species to be added to the reaction. Species to be added are formulated on the basis of atoms present and/or absent in the reaction, along with valence, system features, and a series of flags that determines the cardinality of the possible solution set. Incorporation of the proposed model into an inorganic chemistry formulation system would contribute to the development of powerful computer-assisted learning systems, given the extent of information extracted from a reaction.     

基于相似系统理论的相似度计算方法的改进

针对常用的相似度方法对色谱指纹图谱数据的相对差异响应不灵敏,本文对基于相似系统理论的改良程度相似度的计算方法进行了改进。模拟数据和乳块消片色谱指纹图谱数据计算结果表明,改进后的新改良程度相似度q′可区分与参照样本的总差异相同,但差异分布不同的样本。在共有峰峰面积差异不超过100%的情况下,新改良程度相似度q′计算方法能够更灵敏地反映两样本的峰面积的相对差异。本研究的新改良程度相似度q′能突出组分群中某些组分对既定配比的较大偏离,适用于中药成分群配比波动的控制和中药过程质量控制。     

Computer Animation: A new method for teaching,communication, and representation of knowledge about reactions in heterocyclic chemistry

We propose the use of computer animation techniques for representation of knowledge about organic reactions, in particular as applied to syntheses and transformations of heterocycles. We discuss general questions of the methodology of chemical animation as a new method of communication via electronic journals and an effective teaching method. We illustrate the technical and methodological means allowing us to solve the resulting problems, using as an example the operation of a specific program.M. V. Lomonosov State University, Moscow 119899. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1141–1145, August, 1995. Original article submitted July 28, 1995.     

Data,knowledge and method bases in chemical sciences. Part IV. Current status in databases

Computer readable databases have become an integral part of chemical research right from planning data acquisition to interpretation of the information generated. The databases available today are numerical, spectral and bibliographic. Data representation by different schemes--relational, hierarchical and objects--is demonstrated. Quality index (QI) throws light on the quality of data. The objective, prospects and impact of database activity on expert systems are discussed. The number and size of corporate databases available on international networks crossed manageable number leading to databases about their contents. Subsets of corporate or small databases have been developed by groups of chemists. The features and role of knowledge-based or intelligent databases are described.     

A simple algorithm for unique representation of chemical structures-cyclic/acyclic functionalized achiral molecules

An algorithm, based on "vertex priority values" has been proposed to uniquely sequence and represent connectivity matrices of chemical structures of cyclic/acyclic functionalized achiral hydrocarbons and their derivatives. In this method, "vertex priority values" have been assigned in terms of atomic weights, subgraph lengths, loops, and heteroatom contents. Subsequently, the terminal vertices have been considered upon completing the sequencing of the core vertices. This approach provides a multilayered connectivity graph, which can be put to use in comparing two or more structures or parts thereof for any given purpose. Furthermore, the basic vertex connection tables generated here are useful in the computation of characteristic matrices/topological indices and automorphism groups and in storing, sorting, and retrieving chemical structures from databases.