Discovering new membrane protein functions with multi-scale molecular simulations.

Cellular membranes play a huge role in a myriad of key cellular processes as diverse and fascinating as vesicle trafficking, receptor functioning or synaptic transmission. Yet, due to intrinsic limitations of biophysical and biochemical methods when dealing with a membrane- mimetic environment, a high-resolution knowledge of the basic physicochemical principles that govern these processes is still limited. In this context, in silico modeling is a well-established alternative strategy, since computational-based studies offer the possibility to investigate the behavior of matter directly at the atomistic level under highly controlled conditions.
In this contribution, I will present recent results from our lab showing how recent developments in computational methods have allowed us to gain unprecedented understanding on key cellular processes that are governed by protein-lipid interactions. Specifically, I will discuss various instances in which, via the combination of multi-scale molecular simulations with multiple experimental approaches (in situ cryo-ET, fluorescence microscopy, in vitro functional assays), a detailed molecular understanding of protein-lipid interactions has provided a new understanding of proteins function, including for lipid scramblases and lipid transport proteins.