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Article

A Novel In Silico Approach to Drug Discovery via Computational Intelligence

David Hecht*^† and Gary B. Fogel^‡

Southwestern College, 900 Otay Lakes Road, Chula Vista, California 91910, and Natural Selection, Inc., 9330 Scranton Road, Suite 150, San Diego, California 92121

J. Chem. Inf. Model., 2009, 49 (4), pp 1105–1121

DOI: 10.1021/ci9000647

Publication Date (Web): April 6, 2009

* Corresponding author phone: (619)421-6700; e-mail: dhecht@swccd.edu., †

Southwestern College.

, ‡

Natural Selection, Inc.

Abstract

A computational intelligence drug discovery platform is introduced as an innovative technology designed to accelerate high-throughput drug screening for generalized protein-targeted drug discovery. This technology results in collections of novel small molecule compounds that bind to protein targets as well as details on predicted binding modes and molecular interactions. The approach was tested on dihydrofolate reductase (DHFR) for novel antimalarial drug discovery; however, the methods developed can be applied broadly in early stage drug discovery and development. For this purpose, an initial fragment library was defined, and an automated fragment assembly algorithm was generated. These were combined with a computational intelligence screening tool for prescreening of compounds relative to DHFR inhibition. The entire method was assayed relative to spaces of known DHFR inhibitors and with chemical feasibility in mind, leading to experimental validation in future studies.

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Published In Issue April 27, 2009
Article ASAPApril 06, 2009
Received: February 23, 2009

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Article

A Novel In Silico Approach to Drug Discovery via Computational Intelligence

Abstract

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SciFinder Links

History

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Related Content

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PubChem as a Source of Polypharmacology

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