ISSN:
0020-7608
Keywords:
Chemistry
;
Theoretical, Physical and Computational Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
We describe a new computational approach, called Focus-2D, to the rational design of targeted combinatorial chemical libraries. This approach is based on the hypothesis that structurally similar compounds display similar biological activity profiles. Building blocks that are used in a combinatorial chemical synthesis are randomly assembled to produce virtual library compounds. Individual library compounds are represented by Kier-Hall topological descriptors. Molecular similarities between compounds are evaluated quantitatively by modified pairwise Euclidean distances in multidimensional descriptor space. Simulated Annealing is used to search the potentially large structural space of virtual chemical libraries in order to identify compounds similar to lead molecules. Frequency analysis of building block composition of selected virtual compounds identifies the building blocks that can be used in combinatorial synthesis of chemical libraries with a high similarity to the lead molecules. We show that this method correctly identifies the building blocks found in active peptoids with opioid activities. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 69: 65-75, 1998
Additional Material:
9 Ill.
Type of Medium:
Electronic Resource
