Genick, Christine, Ottl, Johannes and Scheufler, Clemens (2014) Applications of Biophysics in High Throughput Screening Hit Validation. Journal of Biomolecular Screening, 19 (5). pp. 707-714. ISSN 1087-05711552-454X

Abstract

For approximately a decade, biophysical methods have been utilized to validate positive hits selected from high throughput screening campaigns with the goal to verify binding interactions using label-free assays. By applying label-free readouts, screen artifacts created by compound interference and fluorescence are discovered, enabling further characterization of the hits for their target specificity and selectivity. The use of several biophysical methods to extract this type of high content information is required in order to prevent the promotion of false positives to the next level of hit validation and to select the best candidates for further chemical optimization. The typical technologies applied in this arena include DLS (Dynamic Light Scattering), Turbidometry, RWG (Resonance Waveguide Grating), SPR (Surface Plasmon Resonance), DSF (Differential Scanning Fluorimetry), MS (Mass Spectrometry), and others. Each technology can provide different types of information of the binding interaction of interest. Thus, these technologies can be incorporated in a hit validation strategy according to the profile of chemical matter that is desired by the medicinal chemists and naturally to the amenability of the target protein to the technology’s screening format. Here we present the results of several screening strategies using biophysics with the objective to compare their approaches, discuss their advantages and challenges, and summarize their benefits in reference to lead discovery.

Item Type:	Article
Additional Information:	This manuscription should be submitted by Friday, August 16, 2013.
Date Deposited:	14 Jun 2016 23:45
Last Modified:	04 Jul 2016 23:45
URI:	https://oak.novartis.com/id/eprint/20245