Séminaire de l'Institut de Chimie Physique par Tâp HA-DUONG - vendredi 6 mars 2020 à 14h
Tâp HA-DUONG, BioCIS, Université Paris Saclay
Vendredi 6 mars à 14h (salle Magat)
"Intrinsically disordered proteins : How to hit a moving target in drug design ?"
Résumé
Intrinsically disordered proteins (IDPs) are characterized by one or several regions which lack stable secondary and tertiary structure in their unbound state under physiological conditions. They frequently play crucial roles in the regulation of many biological processes and, to exert their functions, interact with several molecular partners.
Due to their large conformational heterogeneity, the structural characterization of IDPs and their complexes is very challenging using classical X-ray crystallography or NMR HSQC spectroscopy. Nevertheless, NMR secondary chemical shifts provide local information about the propensity of each residue to form transient secondary structures, and small-angle X-ray scattering (SAXS) can deliver global information in terms of average size and shape. However, in order to infer a detailed conformational ensemble from NMR and SAXS data, it is most often necessary to use complementary in silico approaches to generate structures at atomic level, such as statistical coil generator or molecular dynamics (MD) simulations.
We present here some of these approaches to generate and characterize the conformational ensemble of IDPs and IDP-protein complexes with a view to providing structural bases for the development of ligands capable of modulating their biological activities.
Bâtiment 349 - rue Michel Magnat - OrsayTâp HA-DUONG, BioCIS, Université Paris Saclay
Vendredi 6 mars à 14h (salle Magat)
"Intrinsically disordered proteins : How to hit a moving target in drug design ?"
Résumé
Intrinsically disordered proteins (IDPs) are characterized by one or several regions which lack stable secondary and tertiary structure in their unbound state under physiological conditions. They frequently play crucial roles in the regulation of many biological processes and, to exert their functions, interact with several molecular partners.
Due to their large conformational heterogeneity, the structural characterization of IDPs and their complexes is very challenging using classical X-ray crystallography or NMR HSQC spectroscopy. Nevertheless, NMR secondary chemical shifts provide local information about the propensity of each residue to form transient secondary structures, and small-angle X-ray scattering (SAXS) can deliver global information in terms of average size and shape. However, in order to infer a detailed conformational ensemble from NMR and SAXS data, it is most often necessary to use complementary in silico approaches to generate structures at atomic level, such as statistical coil generator or molecular dynamics (MD) simulations.
We present here some of these approaches to generate and characterize the conformational ensemble of IDPs and IDP-protein complexes with a view to providing structural bases for the development of ligands capable of modulating their biological activities.