TY - JOUR

T1 - Specific interactions of peripheral membrane proteins with lipids

T2 - what can molecular simulations show us?

AU - Larsen, Andreas H

AU - John, Laura H

AU - Sansom, Mark S P

AU - Corey, Robin A

N1 - © 2022 The Author(s).

PY - 2022

Y1 - 2022

N2 - Peripheral membrane proteins (PMPs) 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 PMP 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 phosphatidylinositol phosphate (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.

AB - Peripheral membrane proteins (PMPs) 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 PMP 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 phosphatidylinositol phosphate (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.

KW - Binding Sites

KW - Cell Membrane/metabolism

KW - Lipids/analysis

KW - Membrane Proteins/metabolism

KW - Molecular Dynamics Simulation

KW - Protein Binding

U2 - 10.1042/BSR20211406

DO - 10.1042/BSR20211406

M3 - Journal article

C2 - 35297484

VL - 42

JO - Bioscience Reports

JF - Bioscience Reports

SN - 0144-8463

IS - 4

ER -