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RESEARCH PRODUCT

From Hydrophobic Matching to Interfacial Tuning: New Ideas for the Mutual Adaptation Between Membranes and Peptides

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It is widely accepted that membrane proteins and lipid bilayers are complementary in terms of the distribution in space of their hydrophobic and polar regions. Similarly, it is also accepted that the hydrophobic parts of the protein and the membrane must adapt to each other. Classically these ideas are rationalized under the concept of hydrophobic matching, which predicts a number of possible mechanisms by which proteins can vary their effective hydrophobic length, or membranes can change their hydrophobic thickness. Such effects have been studied in detail for simplified systems, like transmembrane peptides or protein fragments, which generally show that optimizing peptide orientation is the principal adaptation response.Based on simple computational methods, we show that the relative positioning, including orientation, of a peptide in a membrane can be easily and accurately predicted if the bilayer interfaces are taken into account. This allows studying in detail the adaptations of peptides to membranes, showing that, together with the classical coarse adjustment achieved by changes of the peptide tilt, there can be fine tuned adjustments through the azimuthal rotation. The latter tuning effect occurs mainly by optimizing positions of residues near the interface, and because it involves small changes of free energy, it provides a mechanism for high peptide dynamics. Additionally it strengthens the importance of the bilayer interface for the mutual adaptation of membranes and proteins and gives a new framework for the definition of so called flanking (or anchoring) residues.