1. Peptide partitioning and folding into lipid bilayers
- Author
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Ulmschneider, Jakob P., Doux, Jacques P F, Killian, J. Antoinette, Smith, Jeremy C., Ulmschneider, Martin B., Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Sub Membrane Biochemistry & Biophysics, and Membrane Biochemistry and Biophysics
- Subjects
Physics::Biological Physics ,Quantitative Biology::Biomolecules ,Circular dichroism ,Chemistry ,Bilayer ,Force field (chemistry) ,Computer Science Applications ,Quantitative Biology::Subcellular Processes ,Microsecond ,Molecular dynamics ,Crystallography ,Membrane ,Chemical physics ,Physical and Theoretical Chemistry ,Lipid bilayer ,Protein secondary structure - 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 allatom 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. © 2009 American Chemical Society.
- Published
- 2009