Current Status of Molecular Dynamics Simulations of Membrane Permeabilization by Antimicrobial Peptides and Pore-Forming Proteins: A Review

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Biological membranes are crucial for cellular integrity and function, but their selective permeability can be compromised by various peptides and proteins, such as antimicrobial peptides (AMPs) and pore-forming proteins/toxins (PFPs/PFTs). These molecules induce membrane permeabilization through diverse mechanisms, ranging from the formation of well-defined pores to more nuanced disruptions of the lipid bilayer. Understanding molecular mechanisms underlying membrane integrity disruption is vital for developing novel tools to be applied in medicine, biotechnology, and agriculture. However, due to their transient and dynamic nature, characterizing membrane-disrupting mechanisms is a significant experimental challenge. In silico methods, particularly all-atom and coarse-grained molecular dynamics (MD) simulations, are an indispensable tool to complement and enrich experimental studies, and can offer detailed insights into peptide/protein–membrane interactions, insertion, oligomerization, and pore formation. This review provides a comprehensive overview of the structural and mechanistic diversity of AMPs and PFPs, highlighting representative case studies and discussing key challenges emerging from MD simulations.