Understanding Periperal Membrane Protein Interactions | BPS Thematic Meeting

Understanding Peripheral Membrane Protein Interactions: Structure, Dynamics, Function and Therapy

Tuesday Speaker Abstracts

ENERGETICS OF SIDE CHAIN PARTITIONING ACROSS THE BILAYER INTERFACE Karen G. Fleming ; 1 Johns Hopkins University, Biophysics, Baltimore, MD, USA The chemical composition of the bilayer interface is complex and is characterized by a steep polarity gradient dominated by a continuously changing water concentration. The concentration of water alone changes by orders of magnitude over an the extremely small distance of ~15 to 30 Å. This environment modulates the molecular forces stabilizing the membrane interactions with proteins. We have addressed this fundamental question on protein interactions with the membrane periphery by measuring the stabilities of protein side chains across the bilayer interface using a combination of experiment and simulation. Our data shows that they “hydrophobic effect” is not one effect but rather continuously changes with the interfacial polarity gradient. we have discovered a nonpolar solvation function demonstrating an empirical correlation between the surface area of the nonpolar side chain, their free energies of interface insertion, and the local water concentration in the membrane. This new function allows side chain partitioning to be accurately estimated at any location in the bilayer. At the bilayer interface surface, we find a nonpolar hydrophobicity scale similar to the “biological”, translocon based transfer free energies, indicating that the translocon energetically mimics the bilayer interface. In contrast, at the central position of the bilayer, hydrophobicity energies are twice as stabilizing for nonpolar side chains. Together these findings can be applied to increase the accuracy of computational workflows used to identify and design membrane proteins as well as bring greater insight into our understanding of how disease-causing mutations a ff ect membrane protein folding and function.

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