title: Determining the optimal size of small molecule mixtures for high throughput NMR screening.
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.
authors.affiliation: Department of Chemistry, University of Nebraska Lincoln, 722 Hamilton Hall, Lincoln, NE 68522-0304, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Mercier
authors.forename: Robert
authors.initials: R
authors.lastname: Powers
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003080:Cold Temperature; D015195:Drug Design; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011237:Predictive Value of Tests; D011522:Protons; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D004364:Pharmaceutical Preparations; D011522:Protons