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PMID: 15803397 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Journal of biomolecular NMR ·Vol. 31 ·No. 3 ·2005-03-00 ·Pages 243-58

Mercier KA, Powers R

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.

MeSH Terms
Chemistry, Pharmaceutical/methods Cold Temperature Drug Design Drug Stability Hydrogen-Ion Concentration Magnetic Resonance Spectroscopy/methods Models, Chemical Pharmaceutical Preparations/chemistry Predictive Value of Tests Protons Solubility Structure-Activity Relationship
Chemicals
Pharmaceutical Preparations Protons
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Mercier Kelly A
Department of Chemistry, University of Nebraska Lincoln, 722 Hamilton Hall, Lincoln, NE 68522-0304, USA.
Powers Robert
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Article Info
Journal
Journal of biomolecular NMR
Abbr.
J Biomol NMR
ISSN
0925-2738
DOI
10.1007/s10858-005-0948-4
Published
2005-03-00
Pages
243-58
Language
English
Region
Netherlands
NLM ID
9110829
Subset
IM
Grants
NIGMS NIH HHS · P50 GM62413 · United States
External Links
PubMed source DOI: 10.1007/s10858-005-0948-4 View journal details
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