@inbook{304a4360b51b47039c908fbcbc9bab0e,
title = "Applying HT-SAXS to chemical ligand screening",
abstract = "Chemical probes are invaluable tools for investigating essential biological processes. Understanding how small-molecule probes engage biomolecular conformations is critical to developing their functional selectivity. High-throughput solution X-ray scattering is well-positioned to profile target-ligand complexes during probe development, bringing conformational insight and selection to traditional ligand binding assays. Access to high-quality synchrotron SAXS datasets and high-throughput data analysis now allows routine academic users to incorporate conformational information into small-molecule development pipelines. Here we describe a general approach for benchmarking and preparing HT-SAXS chemical screens from small fragment libraries. Using the allosteric oxidoreductase Apoptosis-Inducing Factor (AIF) as an exemplary system, we illustrate how HT-SAXS efficiently identifies an allosteric candidate among hits of a microscale thermophoresis ligand screen. We discuss considerations for pursuing HT-SAXS chemical screening with other systems of interest and reflect on advances to extend screening throughput and sensitivity.",
keywords = "AIF, Allostery, Chemical screening, Drug discovery, Fragment libraries, HT-SAXS, Redox, X-ray scattering",
author = "Brosey, {Chris A.} and Runze Shen and Davide Moiani and Jones, {Darin E.} and Kathryn Burnett and Hura, {Greg L.} and Tainer, {John A.}",
note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",
year = "2023",
month = jan,
doi = "10.1016/bs.mie.2022.09.022",
language = "English (US)",
isbn = "9780323991810",
series = "Methods in Enzymology",
publisher = "Academic Press Inc.",
pages = "331--350",
editor = "Tainer, {John A.}",
booktitle = "Small Angle Scattering Part B",
}