Journal of Biomolecular NMR

, Volume 31, Issue 3, pp 243–258 | Cite as

Determining the optimal size of small molecule mixtures for high throughput NMR screening

Article

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.

Key words

optimal mixture size NMR screening high-throughput NMR screening NMR mixtures 

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Copyright information

© Kluwer Academic Publishers 2005

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of Nebraska LincolnLincolnU.S.A

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