Modeling Protein–Micelle Systems in Implicit Water

Abstract

Several membrane proteins and numerous membrane-active peptides have been studied in detergent micelles by solution NMR. However, the detailed structure of these complexes remains unknown. We propose a modeling approach that treats the protein and detergent in atomistic detail and the solvent implicitly. The model is based on previous work on dodecylphosphocholine micelles, adapted for use with the CHARMM36 force field and extended to sodium dodecyl sulfate micelles. Solvation parameters were slightly adjusted to reproduce experimental data on aggregation numbers and critical micelle concentrations. To test the approach, several membrane-active peptides and three β-barrel membrane proteins were subjected to molecular dynamics simulations in the presence of a large number of detergent molecules. Their experimentally determined secondary structure was maintained and the RMSD values were less than 2 Å. Deformations were commonly observed in the N or C termini. The atomistic view of the protein-micelle systems that this approach provides could be useful in interpreting biophysical experiments carried out in the presence of detergent.

Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies

“… 474 Turning to an implicit-solvent description, Versace and Lazaridis examined a variety of interfacial peptides and β-barrel MPs in both DPC and SDS micelles, and noted little conformational deformation with respect to the reference, experimental structures. 478 In their investigation of the N-terminal region of hemagglutinin in DPC micelles and in a DMPC bilayer, Victor et al showed that this fusion peptide remains fully structured in the detergent medium, and adopts a membrane-spanning conformation in the bilayer, distorting locally the latter. 479 Im and co-workers have designed a convenient tool for the construction of detergent micelles hosting proteins and peptides, and have applied it to the systematic study of a voltage-dependent potassium channel and the papiliocin peptide, showing an asymptotic limit of the protein–detergent interactions with the number of both DPC and DHPC detergent molecules.…”

Application of the Fuzzy Oil Drop Model Describes Amyloid as a Ribbonlike Micelle

“…A local deficit of hydrophobicity typically marks a ligand binding cavity [8] while excess hydrophobicity-if present on the surface-may indicate a complexation site [9,10]. Other models oriented on micellar organization deal with dynamic forms [11], including micellar aggregates studied in the context of membrane proteins [12,13]. Studies of micellar forms and their applications in drug transport can be found in [14][15][16][17][18][19].…”

Backbone structure of Yersinia pestis Ail determined in micelles by NMR-restrained simulated annealing with implicit membrane solvation

“…In the case of detergent micelles, the structure of the hydrophobic environment departs even further from the continuous membrane model of eefxPot , as it is far from planar, much more fluid, and contains much more water than a lipid bilayer. A solution to this problem may be to perform calculations where the water phase is represented implicitly with eefxPot , and both the protein and the detergent molecules are treated in atomistic detail, as described for molecular dynamics (MD) simulations (Versace and Lazaridis 2015). …”