Computer simulations of lipid membranes and their interactions with proteins and nanoparticles

Membranes are multi-component lipid bilayers that are a crucial component of every cell. They act as a physical barrier protecting the cell, compartmentalize organelles, and control the movement of substances through them. Cells modulate local membrane properties by changing their lipid compositions and lateral organization. Lipids also localize and interact with proteins for many cellular processes like signaling, membrane remodeling, and trafficking.

Experimental techniques face inherent limitations in directly studying membranes at the nanoscale. Molecular dynamics (MD) simulations have emerged as a powerful computational tool that complements experimental studies by providing molecular-level insights into membrane behavior and interactions. MD simulations can elucidate how individual lipid molecules move, fluctuate, and interact with each other, and how proteins interact with lipid membranes at the atomic scale.

The research presented in this thesis leverages MD simulations to investigate several biologically relevant membrane systems. We use all-atom MD to investigate how the composition of membranes containing branched-tail lipids and cardiolipin affects properties of model bacterial membranes. Using all-atom MD, we identify how the dysferlin domain of Pex30 and the MreB extended N-terminal region interact with membranes of different compositions. We use coarse-grained MD to investigate the aggregation of curvature-inducing transmembrane proteins and of deformable nanoparticles anchored to the membrane with cholesterol.