Method development for the identification and characterization of low-affinity ligand-binding sites on protein targets using X-ray crystallography

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The grant proposal consists in establishing a method to locate and characterize the binding pockets of smallmolecule ligands (so called fragments) onto a protein target, at atomic resolution. NMX Research andSolutions Inc. is a research organization specialized in drug discovery and fragment screening using nuclearmagnetic resonance spectroscopy. The company aims at developing novel methods for the screening offragment and small molecule onto proteins. Such challenging project requires highly sensitive biophysicalmethods to obtain high-resolution structural information. Hence, understanding how low-affinity fragmentsbind to proteins remains a fundamental question and a technical challenge raised by NMX Research andSolutions. Dr. Calmettes, expert in protein structures and X-ray crystallography, will develop for NMXResearch and Solutions an alternative method to identify and locate low-affinity fragment-binding sites onproteins using protein X-ray crystallography. Only a few groups in Canada have the expertise in preparing,crystallizing, and solving protein structures. This project is highly relevant for the Canadian industry and theadvancement of knowledge in Canada; it is anticipated to open new avenues for the design of protein regulatorfor a variety of applications in biotechnology, bioscience and bio-industrial sectors in Canada.