BPS2026 – Molecular distance perturbations for 2D-COS analysis: Simulations and measurements

Antimicrobial peptides could help address the problem of bacterial drug resistance if their mechanisms for disrupting bacterial membranes are better understood. New techniques are needed to help characterize peptide-lipid systems and understand the mechanisms by which peptides disrupt membranes. We introduce distance perturbations for 2D correlation spectroscopy (2D-COS) to aid in characterizing peptide-lipid systems. The 2D-COS order of positions method links spectral changes to the positions of functional groups in peptide-bilayer systems. As a first step in our exploration, we study the quantum density functional theory normal modes of lipids to model the order of positions for lipid bilayers. The Z coordinate and radial coordinate orders of positions are explored to determine if they can be mapped back to distance-related metrics, such as RMSD. Overall, we are creating a framework to describe the structure and structural distributions from a 2D-COS point of view, which helps describe systems like the peptide-lipid system in terms of an ensemble of important conformations.