Similarity searching in databases of three-dimensional molecules and macromolecules.

This paper discusses algorithmic techniques for measuring the degree of similarity between pairs of three-dimensional (3-D) chemical molecules represented by interatomic distance matrices. A comparison of four methods for the calculation of 3-D structural similarity suggests that the most effective one is a procedure that identifies pairs of atoms, one from each of the molecules that are being compared, that lie at the center of geometrically-related volumes of 3-D space. This atom mapping method enables the calculation of a wide range of types of intermolecular similarity coefficient, including measures that are based on physicochemical data. Massively-parallel implementations of the method are discussed, using the AMT Distributed Array Processor, that achieve a substantial increase in performance when compared with a sequential implementation on a UNIX workstation. Current work involves the use of angular information and the extension of the method to field-based similarity searching. Similarity searching in 3-D macromolecules is effected by the use of a maximal common subgraph (MCS) isomorphism algorithm with a novel, graph-based representation of the tertiary structures of proteins. This algorithm is being used to identify similarities between the 3-D structures of proteins in the Brookhaven Protein Data Bank; its use is exemplified by searches involving the NAD-binding fold motif.     

Chemical valence in SF4 and SF4O

A qualitative molecular orbital treatment is used to correlate the electronic structure with the observed molecular structures of SF₄ and SF₄O.

---

Zusammenfassung Das M. O.-Verfahren wurde auf SF₄ und SF₄O bei Vorgabe der geometrischen Struktur qualitativ angewendet und auf diese Weise Einblick in die Elektronenstruktur gewonnen.

---

Résumé Un traitement qualitatif aux orbitales moléculaires met en corrélation la structure électronique et la géométrie observée de SF₄ et SF₄O.

     

N-Methyl chemical shifts in some 2-, 3- and 4-substituted N-methylpyridinium salts

The chemical shifts of the N-methyl group in a series of 2-, 3- and 4-substituted N-methylpyridinium salts have been measured in DMSO solution. The shift is primarily affected by resonance interaction between the substituent and aza group, and the results suggest that the resonance effect from a 2-substituent is at least as great as from the corresponding 4-substituent.     

Knowledge-based interaction fingerprint scoring: a simple method for improving the effectiveness of fast scoring functions

A new method for the postprocessing of docking outputs has been developed, based on encoding putative 3D binding modes (docking solutions) as ligand-protein interactions into simple bit strings, a method analogous to the structural interaction fingerprint. Instead of employing traditional scoring functions, the method uses a series of new, knowledge-based scores derived from the similarity of the bit strings for each docking solution to that of a known reference binding mode. A GOLD docking study was carried out using the Bissantz estrogen receptor antagonist set along with the new scoring method. Superior recovery rates, with up to 2-fold enrichments, were observed when the new knowledge-based scoring was compared to the GOLD fitness score. In addition, top ranking sets of molecules (actives and potential actives or decoys) were structurally diverse with low molecular weights and structural complexities. Principal component analysis and clustering of the fingerprints permits the easy separation of active from inactive binding modes and the visualization of diverse binding modes.