Abstract
High-throughput screening (HTS) using NMR spectroscopy has become a common component of the drug discovery effort and is widely used throughout the pharmaceutical industry. NMR provides additional information about the nature of small molecule-protein interactions compared to traditional HTS methods. In order to achieve comparable efficiency, small molecules are often screened as mixtures in NMR-based assays. Nevertheless, an analysis of the efficiency of mixtures and a corresponding determination of the optimum mixture size (OMS) that minimizes the amount of material and instrumentation time required for an NMR screen has been lacking. A model for calculating OMS based on the application of the hypergeometric distribution function to determine the probability of a 'hit' for various mixture sizes and hit rates is presented. An alternative method for the deconvolution of large screening mixtures is also discussed. These methods have been applied in a high-throughput NMR screening assay using a small, directed library.
Original language | English (US) |
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Pages (from-to) | 243-258 |
Number of pages | 16 |
Journal | Journal of Biomolecular NMR |
Volume | 31 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2005 |
Keywords
- High-throughput NMR
- NMR screening
- Optimal mixture size
- Screening NMR mixtures
ASJC Scopus subject areas
- Biochemistry
- Spectroscopy