University of Hertfordshire

By the same authors

SkelGen: a general tool for structure-based de novo ligand design

Research output: Contribution to journalLiterature review

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Original languageEnglish
Number of pages11
Pages (from-to)179-189
JournalExpert Opinion on Drug Discovery
Journal publication dateJul 2006
Volume1
Issue2
DOIs
Publication statusPublished - Jul 2006

Abstract

The recent lapse in productivity in the pharmaceutical industry has facilitated the emergence of experimental and in silico structure-based design methodologies, based on identification of biologically active low molecular weight fragments that can be exploited to produce potential drug candidates with diverse chemistries. SkelGen, an in silico example of this methodology, is reviewed. The ability of this algorithm to identify chemically diverse low molecular weight fragments that would potentially bind to DNA gyrase is recounted, as is the first purely de novo structure-based design of five compounds that show at least micromolar activity against the estrogen receptor. The ability of the algorithm to incorporate partial protein flexibility during its design of compounds to the estrogen receptor is discussed, and an opinion as to the near and long-term futures for de novo design algorithms is expressed.

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