Recent advances in modeling membrane beta-barrel proteins using molecular dynamics simulations: from their lipid environments to their assemblies

Spurred by advances in AI-driven modeling and experimental methods, molecular dynamics simulations are now acting as a platform to integrate these different approaches. This combination of methods is especially useful to understand β-barrel proteins from the molecular level, e.g., identifying specific interactions with lipids or small molecules, up to assemblies comprised of hundreds of proteins and thousands of lipids. In this minireview, we will discuss recent advances, mainly from the last five years, in modeling β-barrel proteins and their assemblies. These approaches require specific kinds of modeling and potentially different model resolutions that we will first describe in Section 1. We will then focus on different aspects of β-barrel protein modeling: how different types of molecules can diffuse through β-barrel proteins (Section 2); how lipids can interact with these proteins (Section 3); how β-barrel proteins can interact with membrane partners (Section 4) or periplasmic extensions and partners (Section 5) to form large assemblies.