To be announced

Binding of Small Ligands to Two-state Membrane Proteins

Understanding how lipophilic small ligands impact membrane proteins requires knowledge on the molecular structure of ligand binding, a reasoning that has driven relentless efforts in drug discovery and translational research. Binding of such ligands appears however highly complex involving interactions to multiple transmembrane protein sites featuring single or multiple occupancy states in a concentration-dependent manner – a process that might depend further on chemotypes, protein types and conformations. Looking for new developments in the field, we will present and discuss a statistical mechanical formulation of the equilibrium properties of ligand binding to membrane proteins, clarifying the impact of multiple binding events on the energetics of two-state membrane proteins intrinsically driven by a variety of thermodynamical conjugates. The theory in combination with docking or flooding MD may be of special interest by establishing a microscopic framework to be linked with macroscopic measurements. Illustration of the approach will be presented in the context of anesthetic binding to ion channels, highlighting how such calculations in combination with measurements have been applied to investigate anesthetic action.

Short Bio Werner has a B.S. degree in Biology (1998), Ph.D in Molecular Biology (University of Brasilia, 2003) and Ph.D. in Theoretical and Computational Chemistry (University Henri Poincar√©, 2004). Before becoming¬† an Associate Professor at the University of Brasilia (2009), he was a Post-Doctoral fellow at Tarek’s group (University Henri-Poincar√©, FR) and at Klein’s group (University of Pennsylvania and Institute for Computational Molecular Sciences, US). His research concerns the use of high-resolution crystal structures in combination with MD simulations and an arsenal of cutting-edge MD-related methodologies to investigate the structure and function of membrane proteins and their regulation by ligands.

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