Missing fragments: detecting cooperative binding in fragment-based drug design

Pramod Nair, Alpeshkumar K Malde, Nyssa Drinkwater, Alan E Mark

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)

Abstract

The aim of fragment-based drug design (FBDD) is to identify molecular fragments that bind to alternate subsites within a given binding pocket leading to cooperative binding when linked. In this study, the binding of fragments to human phenylethanolamine N-methyltransferase is used to illustrate how (a) current protocols may fail to detect fragments that bind cooperatively, (b) theoretical approaches can be used to validate potential hits, and (c) apparent false positives obtained when screening against cocktails of fragments may in fact indicate promising leads.
Original languageEnglish
Pages (from-to)322 - 326
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume3
Issue number4
DOIs
Publication statusPublished - 2012
Externally publishedYes

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