Studying the Protein-Membrane Interaction of a Mycobacterial ABC Transporter Through Coarse-Grained Simulations

Direct interactions with the surrounding lipid bilayer are crucial for regulating the function of membrane transporters. These interactions are essential for controlling the conformational changes that drive the transport cycle. From a pharmacological perspective, understanding these specific interactions is crucial because transporters in pathogenic bacteria serve as key targets for the development of new antibiotics. However, experimentally characterizing the specific and transient nature of protein-lipid interactions at a molecular level remains a significant challenge. Coarse-grained (CG) molecular dynamics (MD) simulations have become a popular computational tool, allowing the exploration of long timescales needed to observe the dynamic interplay between proteins and their membrane environments. In this chapter, we will outline a protocol that includes designing, simulating, and analyzing a CG-MD system, with a focus on characterizing protein-lipid interactions. As an example, the simulation of the Mycobacterium tuberculosis siderophore transporter, IrtAB, will be used to demonstrate how to set up and analyze these complex biomolecular systems.