MoLPICS: Molecular insights into Lipid-Protein Interactions in Cellular Signaling

Recent observations suggest that the interplay between biomolecular condensates and biomembranes is crucial for facilitating the transduction of biochemical signals from the external environment to the interior of the cell.

In cell signaling, the binding of ligands to receptors on the plasma membrane initiates a cascade of biochemical events that condensates may aid in propagating deep into the cell.

MoLPICS aims to investigate the mechanisms underlying this regulation of signal transduction through molecular modeling and simulations. The four-year project is organized into four work packages (WPs).

WP1 will introduce lipids into the recently developed CALVADOS model, which accurately and efficiently predicts phase separation of proteins into condensates.

In WP2, conformational ensembles from simulations of membrane proteins at the proteome scale will be used to train a machine learning model, aimed at exploring the connection between genetic variations and clinical phenotypes.

WP3 will combine omics data with molecular simulations to gain insights into how the material properties of multicomponent condensates modulate signaling output. In WP4, simulations of condensates at the interface with biological membranes will shed light on membrane remodeling.

By expanding the complexity of biomolecular systems that can be studied using molecular simulations, MoLPICS will advance our knowledge of the role of biomolecular condensates in cellular signaling in health and disease.