Transmembrane-Peptide Structure Formation from Coarse-Grained Simulations

Abstract

Interfacial systems are at the core of fascinating phenomena in many disciplines, such as biochemistry, soft-matter physics, and food science. However, the parametrization of accurate, reliable, and consistent coarse-grained (CG) models for systems at interfaces remains a challenging endeavor. In this work, we report recent advancements made toward the description of secondary-structure formation of peptides in a membrane environment using CG models. By combining a lipid model that can semi-quantitatively reproduce material properties of a fluid membrane bilayer [1] and a peptide model that is not biased toward one particular state (e.g., alpha-helix or beta-sheet) [2], the combined parametrization [3] allows to look at how peptide structure is affected by the membrane environment on long timescales. We illustrate the robustness of the model by folding different WALP transmembrane helical peptides starting from stretched, unstructured conformations using both simple canonical simulations and enhanced-sampling techniques [4]. Finally, the method is used to fold the 50-residue-long major pVIII coat protein (fd coat) of the filamentous fd bacteriophage. The results show excellent agreement with experimental structures and atomistic simulations in implicit membrane, demonstrating that such a protocol can serve as a starting point for better-refined atomistic simulations in a multiscale framework. [1] Wang and Deserno, J. Phys. Chem. B 114, 11207 (2010). [2] Bereau and Deserno, J. Chem. Phys. 130, 235106 (2009). [3] Bereau, Wang, and Deserno, J. Chem. Phys. 140, 115101 (2014). [4] Bereau and Deserno, submitted.