Atomic-level description of protein–lipid interactions using an accelerated membrane model

Abstract

Peripheral membrane proteins are structurally diverse proteins that are involved in fundamental cellular processes. Their activity of these proteins is frequently modulated through their interaction with cellular membranes, and as a result techniques to study the interfacial interaction between peripheral proteins and the membrane are in high demand. Due to the fluid nature of the membrane and the reversibility of protein–membrane interactions, the experimental study of these systems remains a challenging task. Molecular dynamics simulations offer a suitable approach to study protein–lipid interactions; however, the slow dynamics of the lipids often prevents sufficient sampling of specific membrane–protein interactions in atomistic simulations. To increase lipid dynamics while preserving the atomistic detail of protein–lipid interactions, in the highly mobile membrane-mimetic (HMMM) model the membrane core is replaced by an organic solvent, while short-tailed lipids provide a nearly complete representation of natural lipids at the organic solvent/water interface. Here, we present a brief introduction and a summary of recent applications of the HMMM to study different membrane proteins, complementing the experimental characterization of the presented systems, and we offer a perspective of future applications of the HMMM to study other classes of membrane proteins.

The energetics of protein–lipid interactions as viewed by molecular simulations

“…Considerations of space preclude a more general survey (see e.g. [79][80][81][82][83] for this), so we will focus on one particular example, that of PH ( pleckstrin homology) domains. PH domains are a large and well-characterized family present in many membrane recognition proteins, which can bind to phosphatidylinositol-phosphates (mainly PIP 2 and/or PIP 3 ) in membranes in a specific fashion [84].…”

Direct observation of alpha-lactalbumin, adsorption and incorporation into lipid membrane and formation of lipid/protein hybrid structures

“…The interaction of proteins with cellular membranes controls fundamental cellular processes such as membrane trafficking, cytokinesis, and intracellular signaling [1][2][3][4][5][6][7]. Beside cytoplasmic, peripheral or integral membrane proteins, there is a class of proteins known as amphitropic that interacts with lipids and membranes during their biological activity [8,9].…”

Extension of the Highly Mobile Membrane Mimetic to Transmembrane Systems through Customized in Silico Solvents

“…9–16 However, over the course of a 100 ns MD trajectory, individual lipids may only exchange with their neighbors once or twice, due to a relatively low lateral lipid diffusion constant of ~ 8 × 10 −8 cm 2 s −1 (0.8 Å 2 ns −1 ). 17,18 The resulting membrane representation is effectively static, with the local environment around the protein biased strongly by its initial configuration.…”