Implicit micelle model for membrane proteins using super-ellipsoid approximation

Abstract

Surfactant micelles are often utilized as membrane mimetics for structure determination and functional analysis of membrane proteins. Although curved-surface effects of the micelle can perturb their structure, 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 by introducing a super-ellipsoid approximation to represent the curved-surface effects. Most of the parameters for IMIC are obtained from all-atom explicit solvent MD simulations of twelve membrane proteins in various micelles. In simulations of the HIV envelop protein gp41, M13 major coat protein gp8, and amyloid precursor protein (APP) dimer, curved-surface and compact hydrophobic-core effects are exhibited. The MD simulations with IMIC provide accurate structure predictions of membrane proteins in various micelle environments quickly with smaller computational cost than that necessary for explicit solvent/micelle model. Recent development of automated system builders, such as CHARMM-GUI Micelle builder, 26makes it easy to model a protein-micelle complex for all-atom MD simulations in explicit solvent and micelle. One difficulty, though, is that the aggregation number of surfactant around the protein is usually unknown, and there is limited experimental data available in this regard. [27][28][29][30] To avoid this problem, protocols for the spontaneous formation of the protein-micelle complex have been proposed, where the MD simulation starts from a random distribution of surfactants in the simulation box. [31][32][33] Since such simulations require long relaxation times (typically, several hundred nanoseconds), course-grained models or implicit water models have been employed to enhance