Tetrahedron Computer Methodology最新文献

This paper discusses a procedure for calculating the degree of similarity between an input target molecule and each of the molecules in a database of 3-D chemical structures. A mapping algorithm is used to identify pairs of atoms, one from each of the molecules that are being compared, that lie at the centre of geometrically-related volumes of 3-D space. Techniques are described to increase the run-time efficiency of the basic procedure, so that it can be used for similarity searching in large 3-D databases, and to allow a wide range of types of inter-molecular similarity to be calculated.

A fast ESR spectrum simulation program suitable for radicals in solution is described. The speed of the convolution algorithm is achieved by the use of integer arithmetic and precalculated lineshapes. FDC-ESR is written in C and runs on an IBM PC and ATARI ST (obtain program via TCM-Online) computers. A math coprocessor is not necessary.

The paper gives a brief description of the synthesis planning program RDSS and deals with experience made in application to heterocyclic reactions. The main aim of the undertaken work was the test of the version RDSS V4.1 after completing a new synthon recognition program. A knowledge base consisting of some general synthesis rules and specialized heterocyclic mechanisms was built up to support this task. The results make sure that the knowledge based system RDSS may be a helpful tool for organic synthesis design.

This paper describes a method for the rapid searching of 3d structural databases for molecules showing 3d shape similarity to a query structure. In the sperm program, molecular properties are projected onto the surface of a sphere and icosahedral symmetry is used to minimise storage requirements and accelerate comparison over all of 3d rotational space. The results of searches of a 30,000 compound database for molecules with a 3d shape resembling netropsin and daunomycin are described. In addition to molecules showing topological similarity to the query, hits are obtained showing considerable structural diversity. The results demonstrate that the method might be useful in the selection of new lead compounds as potential ligands for a given receptor.

The first attempt to attack an intriguing inverse problem in QSAR/QSPR is presented. The special technique to the exhaustive targeted search of the structures with a given value of molecular connectivity index is described. The general methodology and the combinatorial algorithm are considered. The selection criteria for the correct generation of graphs and multigraphs with the given distribution of edge types or vertex types are developed. The RING program for the exhaustive generation of structures with the given connectivity index is described, and several examples of its successful application are discussed. A demo version of RING is included in this issue.

The primary importance of molecular fields in biological recognition, attested by the number of reported successful CoMFA applications, suggests possible applications in 3D databases. In further support of this possibility, the probability of chance correlation using PLS in typical CoMFA applications is found to be about 5% or less for a cross-validated r² of 0.3 or greater, a “field fit” strategy for automating the alignment of molecules by seeking minimal differences in their fields is outlined, and a non-biological application of CoMFA, carbonyl hydration, is presented.

The proton NMR spectrum of the conformationally restricted, leukotriene antagonist [(octahydro-2-oxo-7-tetradecylidene-2H-1-benzopyran-8-yl)thio]acetic acid ($\text{3a}$) did not support a chair-chair conformation for the bicyclic ring system as is usually expected. Molecular mechanics and semi-empirical molecular orbital calculations, on the model compounds $\text{3b}$ and $\text{4b}$, indicated that $\text{3a}$ exists in a chair-boat rather than a chair-chair form. The findings of this computational study were confirmed by a subsequent x-ray analysis.

The MACCS-3D program was developed to provide a three-dimensional (3D) structural database system for structure, substructure, geometric, and data searching purposes. Applications of the program include discovery of new drugs and agrochemicals to fit known or postulated pharmacophores, and identification of polymers and commercial chemicals whose physical and chemical properties depend on 3D structural features. This paper presents details of the data structures and algorithms used for 3D structural representation, storage, and searching in MACCS-3D. These include algorithms for exact match, substructure, geometric, submodel, and combined 3D structure-data searching. We also describe mechanisms used for 3D data storage and geometric search keys. Integration of MACCS-3D with new chemical representation and search capabilities of the MACCS-II system are briefly described. Finally, new developments in MACCS-3D are described, in light of current and future trends in 3D searching.

Previous work on reaction similarity was based on co-occurence of structural and reaction center keys between reactions in computer-readable databases of reactions. This work demonstrates that similar reactions can be found, even though they are not computer-readable, through citation analysis. Complete citation search results are included on disk.

The Chapman and Hall Dictionary of Drugs is a source of information on over 6000 drugs and their derivatives. The printed form includes much physical and pharmacological data abstracted from patents as well as 2D drawings. The 2D connection tables were made available to Chemical Design and 3D structures were generated and stored in a ChemDBS-3D database. From the initial stored structure, the 3D conformational distance keys were generated in a second step. The computer resources used are presented and these indicate that scaling the automated build/keying procedures to include several 100,000s of compounds is a practical proposition. Some search examples are used to illustrate the screening effects of 3D key searches and the relative importance of using conformational flexibility in finding new hits.