Room 120 Physics Building
Asst. Prof. Martin B. Ulmschneider, Johns Hopkins University presents: "Validating Atomic Detail Peptide Partitioning Simulations Using Synchrotron Radiation Circular Dichroism Spectroscopy."
Studying how flexible membrane-active peptides interact with fluid-phase biological membranes is important for unraveling the mechanisms of antimicrobial and cell-penetrating peptide activity, as well as understanding how proteins fold and assemble in lipid bilayers. However, the fluidity, chemical complexity, and nanometer-scale dimensions of the membrane environment make studies of peptide-membrane interactions a challenging task.
Here we show that the insertion pathway, transfer energetics, and partitioning kinetics of membrane active peptides into lipid bilayers can be obtained by a combination of synchrotron radiation circular dichroism spectroscopy and direct equilibrium atomic resolution molecular dynamics simulations [1,2]. Remarkably, the results are in close quantitative agreement with in vitro translocon experiments. The insertion probability as a function of peptide length follows two-state Boltzmann statistics and reveal many hitherto unknown atomic-resolution details about the partitioning process. The approach presented provides a useful tool for studying of water-to-bilayer transfer properties of membrane active peptides.