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

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

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

J Biomol NMR. 2005 Mar;31(3):243-58

Authors: Mercier KA, Powers R

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.

PMID: 15803397 [PubMed - indexed for MEDLINE]



Source: PubMed