Three-dimensional Chemical Structures Research Articles

Confocal Image Properties of a Confocal Scanning Laser Visible Light FT-Raman Microscope

The confocal Raman microscope is an instrument designed for acquisition of high-contrast volumetric Raman spectral images of three-dimensional chemical structures. Little effort, however, has gone into the investigation of the spatial imaging properties of this class of confocal microscope. In this paper we present experimental results, obtained with a confocal scanning laser visible light FT-Raman microscope we built, that demonstrates the high depth resolution and enhanced Raman image contrast intrinsic to the confocal Raman microscope design. We explore these microscope properties through a combination of experimental measurement and theory based on a paraxial wave diffraction model.

Similarity searching in files of three-dimensional chemical structures: Comparison of fragment-based measures of shape similarity

This paper compares several fragment-based measures that can be used to quantify the degree of similarity between pairs of three-dimensional (3-D) chemical structures. The fragments that are considered contain two, three, or four atoms and encode distance information, angular information or both but do not involve chemical information such as atomic type. The effectiveness of the various measures is compared using eight literature datasets for which biological-activity data and calculated 3-D structures are available, and a set of carbohydrate structures from the Cambridge Structural Database that have been classified into eight distinct groups. Similarity searches on these datasets suggest that the four-atom fragments are the most effective.

Similarity searching in files of three-dimensional chemical structures. Implementation of atom mapping on the distributed array processor DAP-610, the MasPar MP-1104, and the connection machine CM-200

Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Chem. Inf. Comput. Sci. 1994, 34, 1, 224-231

Pharmacophoric pattern matching in files of three-dimensional chemical structures: Comparison of conformational-searching algorithms for flexible searching

Pharmacophoric pattern matching in files of three-dimensional chemical structures: Comparison of conformational-searching algorithms for flexible searching

Pharmacophoric pattern matching in files of three-dimensional chemical structures: Implementation of flexible searching

The conformational space of a flexible three-dimensional (3D) molecule can be represented for searching purposes by a smoothed bounded distance matrix. Such matrices provide an effective way of carrying out flexible searching, but search times can be very long when compared with rigid searches that take no account of conformational flexibility. This paper considers two techniques for minimizing the computational requirements of flexible searching. In the first part, we compare four different indices that have been suggested for the quantification of molecular flexibility, and demonstrate that they produce comparable rankings of sets of molecules in order of decreasing flexibility. We then demonstrate that the prioritization of a set of structures in order of increasing flexibility can result in substantial re- ductions in the time requirements of flexible searching if some fixed number of hit structures is desired. In the second part, we report an analysis of the 3D crystal structures in the Cambridge Structural Database to generate distance ranges that are tighter than those produced by distance geometry. Experiments with a set of six query phar- macophores demonstrate that use of these tightened ranges results in substantial reductions in search times, but that this may also lead to a reduction in the number of hit molecules obtained from the final conformational search.

Pharmacophoric pattern matching in files of three-dimensional chemical structures: Characterization and use of generalized torsion angle screens

This paper describes the use of generalized torsion angles for the screening of conformational searches in databases of three-dimensional chemical structures. A generalized torsion angle is defined as the dihedral angle between two vectors, A 1-A 2 and A 3-A 4, in which none, some, or all of the vectors A 1-A 2, A 2-A 3, and A 3-A 4 correspond to formal chemical bonds. The screens consist of a set of four atoms together with an associated angular range, and are identified by a statistical analysis of the frequencies of occurrence of these features in the Cambridge Structural Database. These frequencies are discussed, and the effectiveness of the screens is demonstrated by an extensive series of searches for representative pharamacophoric patterns.

Pharmacophoric pattern matching in files of three-dimensional chemical structures: use of bounded distance matrices for the representation and searching of conformationally flexible molecules

This paper discusses the use of bounded distance matrices for the representation of conformationally flexible threedimensional (3D) molecules. It is shown that pharmacophoric pattern searches of databases of flexible 3D molecules represented in this way can be carried out using screen and geometric searching algorithms that are analogous to those used for searching databases of rigid 3D structures. Molecules matching a query pattern after the geometric search must then undergo a final conformational search to determine whether they can, in fact, adopt a conformation that matches the query. An analysis of this three-stage searching procedure shows that searching databases of flexible 3D molecules is extremely demanding of computational resources.

Pharmacophoric pattern matching in files of three-dimensional chemical structures: Characterization and use of generalized valence angle screens

This paper describes the use of generalized valence angles for the screening of pharmacophoric pattern searches in databases of three-dimensional chemical structures. A generalized valence angle is defined as the angle between two vectors, AB and BC, which have a common vertex B, and in which both vectors correspond to formal chemical bonds; one vector corresponds to a bond and the other to a nonbonded interaction; or both vectors correspond to non-bonded interactions. The screens are identified by a statistical analysis of the frequencies of occurrence of these anglebased features in the Cambridge Structural Database. The occurrence frequencies are discussed and shown to be explicable in terms of small, commonly occurring structural features. The effectiveness of the screens is demonstrated by an extensive series of searches for representative pharmacophoric patterns. The results are compared with those obtained from a similar series of searches using distancebased screens: The latter are found to give a better level of performance, and evidence is presented to suggest that this is due to a high degree of association between the assignments of the angle-based screens.

Pharmacophoric pattern matching in files of three-dimensional chemical structures: use of smoothed bounded distances for incompletely specified query patterns

This paper describes a technique for increasing the screen out of pharmacophoric pattern searches in the databases of three-dimensional chemical structures when only some of the interatomic distances in the query pattern are specified. The technique involves the application of a distance bounds smoothing procedure to the query distances; this smoothing allows the calculation of upper and lower bounds for the unspecified distances. The bounded distances can then be used to set screens additional to those that are set to describe the distances that have been specified by the searcher. Evidence is presented to suggest that use of the technique can lead to increases in the efficiency of substructure searches for partially specified query patterns.

Identifying 3D maximal common substructures using transputer networks

This paper describes the use of a multiprocessor system for identifying the maximal common substructure (MCS) between pairs of three-dimensional (3D) chemical structures. The system is constructed from Transputers, 32-bit RISC microprocessors produced by Inmos Ltd., linked together in a tree network. The MCS algorithm used, developed by Crandell and Smith, identifies the MCS by a breadth-first search in which individual atoms common to the structures are extended one atom at a time until no further extension of the common substructure can be obtained. Experiments using a Pascal-based simulation package demonstrate the feasibility of using a multiprocessor system to increase the speed of MCS identification. Experiments with networks of Transputers demonstrate that substantial increases in speed can be achieved in practice if, and only if, the MCS is large.

Current research into chemical and textual information retrieval at the department of information studies, University of Sheffield

This paper discusses research into chemical information and document retrieval systems at the Department of Information Studies, University of Sheffield. The research includes the use of cluster analysis methods for document retrieval and drug design, the representation and searching of files of generic chemical structures, substructure searching and maximal common substructure identification in files of three-dimensional chemical structures, and the use of novel parallel computer hardware in all of these application areas.