| | | | | | | webmail : intra-extra| Accès VPN| Accès IST| Contact | English
Univ. Paris-Saclay
Neutron protein crystallography reveals molecular details of inhibitor binding to clinical targets
Zöe Fisher
Mercredi 11/11/2020, 15:00-16:01

Ligand binding to proteins are mediated through numerous interactions. These can include direct hydrogen bonds, water-mediated interactions, electrostatics, metal coordination, energetic changes through water displacement, aromatic ring stacking, and hydrophobic interactions.

Using X-ray crystallography as a tool for the study of protein: ligand complexes is a powerful and high throughput approach, but cannot elucidate many of the atomic details of the types of interactions involved. Neutrons can fill this knowledge gap as they have unique properties that enable us to determine the location of light atoms [1H (Hydrogen), and its isotope 2H (Deuterium)]. By extension then it is possible to observe hydrogen bonds and infer electrostatics based on presence or absence of a hydrogen atoms on the protein but also the ligand. This can inform the researcher on the charged state of a ligand, the involvement of water molecules, and the charged state of amino acid side chains involved in binding.

Combining the unique information from neutron crystallography with high resolution X-ray crystallography, it is then possible to obtain a complete and accurate view of the interactions that drive ligand binding. This talk will include examples from the literature on where this strategy was employed to investigate novel compounds binding to a cancer metastasis marker, and clinically used protease inhibitors to HIV protease.


Contact : Alain MENELLE



Retour en haut