Abstract
The folding and partitioning of WALP peptides into lipid bilayers is characterized using atomic detail molecular dynamics simulations on microsecond time scales. Elevated temperatures are used to increase sampling, and their suitability is validated via circular dichroism experiments. A new united atom parametrization of lipids is employed, adjusted for consistency with the OPLS all-atom force field. In all simulations secondary structure forms rapidly, culminating in the formation of the native trans-membrane helix, which is demonstrated to have the lowest free energy. Partitioning simulations show that peptide insertion into the bilayer is preceded by interfacial folding. These results are in excellent agreement with partitioning theory. In contrast, previous simulations observed unfolded insertion pathways and incorrectly report stable extended configurations inside the membrane. This highlights the importance of accurately tuning and experimentally verifying force field parameters against microsecond time scale phenomena.
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