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J Membrane Biol (2011) 239:1526 DOI 10.1007/s00232-010-9324-8
Determining Peptide Partitioning Properties via Computer Simulation
Jakob P. Ulmschneider Magnus Andersson
Martin B. Ulmschneider
Received: 15 September 2010 / Accepted: 5 November 2010 / Published online: 25 November 2010 The Author(s) 2010. This article is published with open access at Springerlink.com
Abstract The transfer of polypeptide segments into lipid bilayers to form transmembrane helices represents the crucial rst step in cellular membrane protein folding and assembly. This process is driven by complex and poorly understood atomic interactions of peptides with the lipid bilayer environment. The lack of suitable experimental techniques that can resolve these processes both at atomic resolution and nanosecond timescales has spurred the development of computational techniques. In this review, we summarize the signicant progress achieved in the last few years in elucidating the partitioning of peptides into lipid bilayer membranes using atomic detail molecular dynamics simulations. Indeed, partitioning simulations can now provide a wealth of structural and dynamic information. Furthermore, we show that peptide-induced bilayer distortions, insertion pathways, transfer free energies, and kinetic insertion barriers are now accurate enough to complement experiments. Further advances in simulation methods and force eld parameter accuracy promise to turn molecular dynamics simulations into a powerful tool for investigating a wide range of membrane active peptide phenomena.
Keywords Biophysical techniques in membrane research
Membrane structure (protein and lipid diffusion)
Structure of membrane proteins Peptide partitioning
Water to bilayer transfer of peptides
The Importance of Peptide Partitioning Studies
Membrane protein folding and assembly is thought to be a two-stage process in which transmembrane (TM) helices are rst individually established in the bilayer and subsequently rearranged to form the functional protein (Jacobs and White 1989; Popot and Engelman 1990). However, because of the complex and highly dynamic interactions of peptides with the lipid bilayer environment, the mechanisms and energetics underlying this process are poorly understood. In this review, we summarize recent computational efforts to estimate the free energy of transfer of polypeptide segments into membranes. Precise partitioning energetics provide fundamental insights into the folding and assembly process of membrane proteins. Moreover, such knowledge will signicantly improve existing computational methodologies (e.g., force elds) for ab initio structure prediction and simulation of membrane proteins.
Current experimental techniques lack the combination of spatial (atomic)...