Roland Stote
Affiliation
Institute of Genetics and Molecular and Cellular Biology, Strasbourg, France - Reseacrh
Nuclear Receptors in Motion: Shape-Shifts and Dynamics
Co-authors
Ana Milinski1, Valentin Loux1, Meilin An1, Annick Dejaegere1, Roland H. Stote1
1Université de Strasbourg, CNRS, Inserm, IGBMC UMR 7104, UMR-S 1258, F-67400 Illkirch, France
Abstract
Nuclear receptors are ligand-regulated transcription factors that control key physiological processes, including metabolism, development, and cellular homeostasis. Although experimental structures have revealed detailed static snapshots of these proteins, the functionality of nuclear receptors relies on their ability to explore a wide range of conformations and dynamics. Classical molecular dynamics simulations, and particularly enhanced sampling methods, allow one to explore conformational space beyond known static structures, but often validation of the results is lacking. An important way to validate molecular dynamics simulation is by connecting with experimental results.
Following an introduction to the role of structural dynamics in nuclear receptor function, this talk will present ongoing efforts in our team that aim to integrate molecular dynamics simulations with novel experimental approaches, such as far-IR spectroscopy and hydrogen/deuterium exchange mass spectrometry. The synergy developed in such an approach can further enhance the understanding of conformation dependent protein dynamics, while at the same time, providing atomistic information for the interpretation of the experimental results.