title: Free energy of WALP23 dimer association in DMPC, DPPC, and DOPC bilayers.
abstract: The MARTINI coarse-grained model is used to gain insight into the association of WALP23 helices in three different lipid membranes: DMPC, DPPC and DOPC. Potentials of mean force describing the association of two WALP23 helices embedded in different lipid bilayers indicate no barrier of association and a stabilization of more than 20 kJ mol(-1) of the associated state relative to the fully dissociated state. Association is strongest in DMPC, followed by DPPC and DOPC. Helix-helix association appears to be enthalpically favorable in all lipid bilayers, while the entropic contribution appears favorable only in the presence of significant positive hydrophobic mismatch, in DMPC lipids. The interpretation of this requires care given the coarse-grained nature of the simulations, but the sign of the thermodynamic quantities agrees with experimental measurements on dimerization of (AALALAA)3 peptides and the observed association free energies are within the experimental range. Both protein-protein and lipid-lipid interactions appear to strongly favor protein dimerization, while the interactions between a dimer and lipid are unfavorable relative to the interactions between two separated monomers and lipids. Dimers with antiparallel orientation appear to be thermodynamically favored over parallel dimers, particularly in conditions of greater hydrophobic mismatch, but elucidating the detailed origin of this likely requires simulations of helices for which there is structural data on the dimer. We analyze 3D density, membrane order, and membrane thickness maps using new freely available analysis programs. Although these properties differ somewhat for each lipid, perturbations extend to about 1 nm for lipid density, ~2 nm for ordering and ~2.5 nm for thickness. A striking feature is the appearance and extent of systematic density fluctuations around the helices.
authors: Department of Biological Sciences and Institute for Biocomplexity and Informatics, University of Calgary, 2500 University Drive N.W., Calgary, Alberta T2N 1N4, Canada.
authors: Norberto
authors: N
authors: Castillo
authors: Luca
authors: L
authors: Monticelli
authors: Jonathan
authors: J
authors: Barnoud
authors: D Peter
authors: DP
authors: Tieleman
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D004134:Dimyristoylphosphatidylcholine / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D010455:Peptides; D010713:Phosphatidylcholines; C571014:WALP23; D015060:1,2-Dipalmitoylphosphatidylcholine; C017251:1,2-oleoylphosphatidylcholine; D004134:Dimyristoylphosphatidylcholine