Specific interactions of peripheral membrane proteins with lipids: what can molecular simulations show us?

Abstract

Peripheral membrane proteins can reversibly and specifically bind to biological membranes to carry out functions such as cell signalling, enzymatic activity, or membrane remodelling. Structures of these proteins and of their lipid-binding domains are typically solved in a soluble form, sometimes with a lipid or lipid headgroup at the binding site. To provide a detailed molecular view of peripheral membrane protein interactions with the membrane, computational methods such as molecular dynamics (MD) simulations can be applied. Here, we outline recent attempts to characterise these binding interactions, focusing on both intracellular proteins, such as PIP-binding domains, and extracellular proteins such as glycolipid-binding bacterial exotoxins. We compare methods used to identify and analyse lipid binding sites from simulation data and highlight recent work characterising the energetics of these interactions using free energy calculations. We describe how improvements in methodologies and computing power will help MD simulations to continue to contribute to this field in the future.

A Coarse-Grained Molecular Dynamics Investigation on Spontaneous Binding of Aβ1-40Fibrils with Cholesterol-mixed DPPC Bilayers

“…Indeed, these data are in agreement with the previous CG study of Dias et al, which showed spontaneous binding of Aβ 1-42 fibrils with membrane [21]. Our simulations reveal that both charged and hydrophobic residues participate in the binding with the membrane, in agreement also with previous studies reporting that both basic and hydrophobic amino acid residues play an important role in peripheral protein binding with the membranes [39,40]. Furthermore, we noticed that C-terminal residues significantly participate in membrane binding, which is also in line with previous studies.…”

A coarse-grained molecular dynamics investigation on spontaneous binding of Aβ1–40 fibrils with cholesterol-mixed DPPC bilayers

“…Indeed, these data are in agreement with the previous CG study of Dias et al, which showed spontaneous binding of Aβ 1–42 fibrils with membrane [21] . Our simulations reveal that both charged and hydrophobic residues participate in the binding with the membrane, in agreement also with previous studies reporting that both basic and hydrophobic amino acid residues play an important role in peripheral protein binding with the membranes [42] , [43] . Furthermore, we noticed that C-terminal residues significantly participate in membrane binding, which is also in line with previous studies.…”

Towards Molecular Understanding of the Functional Role of UbiJ-UbiK2 Complex in Ubiquinone Biosynthesis by Multiscale Molecular Modelling Studies

“…In this section, the main objective is to better understand the interactions between the heterotrimer UbiJ-UbiK 2 and the lipid bilayer membrane. A multi-scale MD simulation approach, i.e., a series of CG and all-atom MD simulations [ 35 ], was used to tackle this question. For both types of MD simulations, the lipid bilayer membrane was described as realistically as possible with a composition of POPE:70, POPG:25, LNDCL2:5.…”