Implicit Micelle Model for Membrane Proteins Using Superellipsoid Approximation.

Takaharu Mori,Yuji Sugita

doi:10.1021/acs.jctc.9b00783

Abstract

Surfactant micelles are often utilized as membrane mimetics for structure determination and functional analysis of membrane proteins. The curved-surface effects of the micelle can perturb membrane protein structure. However, it is difficult to assess such effects and membrane mimetic artifacts by experimental and theoretical methods. Here, we propose an implicit micelle model (IMIC) to be used in molecular dynamics (MD) simulations of membrane proteins. IMIC is an extension of the IMM1 implicit membrane model and additionally introduces a superellipsoid approximation to represent the curved-surface effects. Most of the IMIC parameters are obtained from all-atom explicit solvent MD simulations of 12 membrane proteins in various micelles. The HIV envelope protein gp41, M13 major coat protein gp8, and amyloid precursor protein (APP) dimer are simulated via MD simulations with IMIC. These simulations clearly show how the micelle influences membrane protein structures compared to the bilayer environments. The MD simulations with IMIC provide reliable membrane protein structures in various micelle environments quickly with smaller computational cost than that for an explicit solvent/micelle model.

Highlights

Membrane proteins play important roles in cellular processes like substrate transport, signal transduction, membrane fusion, and cell adhesion
To prepare the initial structure in the implicit micelle model (IMIC) model, the X-ray crystal or NMR structure was placed near the micelle center with the same orientation as in OPM, and rotated about the Z-axis so that the PC1 and PC2 axes of the X,Y-coordinates of the TM atoms were aligned with the X,Y-axes
We introduced a super-ellipsoid function to define the hydrophobic core region of the micelle, and the parameters were derived from all-atom molecular dynamics (MD) simulations of protein-micelle complexes as well as pure micelles

Summary

Introduction

Membrane proteins play important roles in cellular processes like substrate transport, signal transduction, membrane fusion, and cell adhesion. Examples include the LLP-3 domain in the HIV-1 envelope glycoprotein gp[41,12] bacteriophage M13 major coat protein gp[8,13] influenza M2 proton channel,[14] phospholamban,[15, 16] epidermal growth factor receptor (EGFR),[17] and amyloid precursor psorein (APP).[18,19,20] the LLP-3 peptide forms a curved α-helix on the micelle surface, but is straight on the bicelle surface.[12] The M13 major coat protein gp[8] forms various kinked-helix conformations in micelles, while a continuous α-helix predominates in fully hydrated vesicles.[13] This is in contrast to the glycophorin A dimer, the conformation of which is identical in micelles and lipid bilayers, presumably because the two monomers are tightly bound through GxxxG motif interactions.[21] among experimentally determined structures, discrimination between native structures and membrane mimetic artifacts is extremely valuable

Methods

Results

Discussion

Conclusion