Tetrahedron Computer Methodology最新文献

The program ALTONA, written in BASIC, calculates plots of H-C-C-H dihedral angles from proton-proton NMR vicinal coupling constants using an empirically generalized Karplus-type equation, which takes into account the electronegativity and the orientation of the substituents attached to the considered H-C-C-H fragment. Generation of a plot for the fragment results after introduction of the atomic symbols of the substituents (C, H, O, N, S, P, F, Cl, Br, and/or I) and their orientation (+ or −). ALTONA is compiled in Turbo BASIC for PC compatible computers and is included in the present paper as ALTONA.EXE on disk.

HMO version 1.1 performs Hückel molecular orbital calculations on the Macintosh computer for structures containing up to 100 atoms. The program is interactive and simply requires that the structure of the target molecule be drawn and the number of π electrons be specified. The program automatically constructs the secular determinant from the supplied structure and computes the eigenvectors and eigenvalues by the Jacobi diagonalisation method. The program can accommodate various heteroatoms in the calculation. The output of the program can be displayed in graphic and tabular form. The executable program is included on disk.

This paper sets the bases of a new project for machine learning of generic reactions, starting from examples described in the literature. This project aims at resolving the difficulty of building large and coherent knowledge bases for Computer-Assisted Design of Organic Synthesis (CADOS) programs. Among the different steps involved in the generic reaction learning process, our present work studies the parametrization step, i.e., the derivation of generic schemes of reactions from specific examples of reactions. The foundations of the project are presented and the use of the GRAMS program for the generalization of reactions is illustrated.

A neural network has been trained to predict the outcome of a synthesis controlled by several parameters. Furthermore, this ability was used in the search for optimized reaction conditions. Finally, an excellent correlation between predicted yields and experimental results was obtained.

We converted the 2-D chemical structures in the Derwent Standard Drug File database (which also contains the associated pharmacological activities) into two 3-D databases to be searched by the ChemDBS-3D module of the commercial software product Chem-X. One database was created using the Chem-X 2-D to 3-D structure converter and was keyed using ChemDBS-3D for multiple conformations per compound. The other was created using the program concord and was keyed using ChemDBS-3D for a single conformation per compound. We used ChemDBS-3D to search each database for the presence of five pharmacophores. The results were analyzed to determine whether searching a database allowing for multiple conformations per structure yields a greater fraction of compounds with the appropriate activity than searching a database with the single concord built conformation. In general, searching a database with multiple conformations yields a greater number of compounds having the the appropriate activity but with a lower percentage relative to the number of compounds found. Further, the method by which the 3-D structures were generated does affect the search effectiveness.

Stereoscopic pictures illustrating journal articles are relatively common in x-ray crystallographic or molecular mechanics studies. We describe a computer program that translates a stereo picture of a 3D model back into the XYZ coordinates of the model so that the model can be rotated, its energy calculated and detailed information not available from the original paper can be determined. The source code of the program is included on disk as 3D.FOR.

While three-dimensional (3D) searching has emerged as a new and promising approach to computer-aided drug design, the issue of “conformational flexibility” remains an important problem. The approaches to handling this issue include considering conformational flexibility: (1) in the database itself (storage of multiple conformers); (2) in the searching procedure (on-the-fly conformational fitting); and (3) in the search queries (flexible queries). In this paper, we describe an approach using flexible queries to search for conformationally flexible molecules in a database of single 3D conformers. In addition, the utility of flexible queries in searching for commercially available chemicals as a synthetic precursor for rigid-backbone peptide mimetics is exemplified. Search results using this approach are compared with those obtained from pharmacophoric searches.