Setting up all-atom molecular dynamics simulations to study the interactions of peripheral membrane proteins with model lipid bilayers

All-atom molecular dynamics (MD) simulations enable the study of biological systems at atomic detail, complement the understanding gained from experiment, and can also motivate experimental techniques to further examine a given biological process. This method is based on statistical mechanics; it predicts the trajectory of atoms over time by solving Newton’s Laws of motion taking into account all forces. Here, we describe the use of this methodology to study the interaction between peripheral membrane proteins and a lipid bilayer. Specifically, we provide step-by-step instructions to set up MD simulations to study the binding and interaction of the amphipathic helix of Osh4, a lipid transport protein, and Thanatin, an antimicrobial peptide (AMP), with model lipid bilayers using both fully detailed lipid tails and the highly mobile membrane-mimetic (HMMM) method to enhance conformational sampling.