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.
Artymiuk
P J
PJ
Department of Information Studies, Krebs Institute for Biomolecular Research, University of Sheffield, England.
Bath
P A
PA
Grindley
H M
HM
Pepperrell
C A
CA
Poirrette
A R
AR
Rice
D W
DW
Thorner
D A
DA
Wild
D J
DJ
Willett
P
P
Allen
F H
FH
D000465:Algorithms; D001665:Binding Sites; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D016208:Databases, Factual; D046911:Macromolecular Substances; D015394:Molecular Structure; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D046911:Macromolecular Substances; D011506:Proteins