Membrane models for molecular simulations of peripheral membrane proteins

Abstract

Peripheral membrane proteins (PMPs) bind temporarily to the surface of biological membranes. They also exist in a soluble form and their tertiary structure is often known. Yet, their membrane-bound form and their interfacial-binding site with membrane lipids remain difficult to observe directly. Their binding and unbinding mechanism, the conformational changes of the PMPs and their influence on the membrane structure are notoriously challenging to study experimentally. Molecular dynamics simulations are particularly useful to fill some knowledge-gaps and provide hypothesis that can be experimentally challenged to further our understanding of PMP-membrane recognition. Because of the timescales of PMP-membrane binding events and the computational costs associated with molecular dynamics simulations, membrane models at different levels of resolution are used and often combined in multiscale simulation strategies. We here review membrane models belonging to three classes: atomistic, coarse-grained and implicit. Differences between models are rooted in the underlying theories and the reference data they are parameterized against. The choice of membrane model should therefore not only be guided by its computational efficiency. The range of applications of each model is discussed and illustrated using examples from the literature.

Ceramide-1-phosphate transfer protein promotes sphingolipid reorientation needed for binding during membrane interaction

“…The challenges associated with various modeling options involving membrane interaction by lipid transfer proteins and other peripheral membrane proteins have recently been reviewed by ( 58 ). Extensive efforts for the lipid parameterization set have led to widespread use of CHARMM36, which can be applied without the need for an external surface tension while faithfully reproducing the physicochemical properties of a wide variety of lipid bilayers ( 59 , 60 ).…”

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

“…CHARMM36m (54), Amber (55), and OPLS-AA (56). For a more detailed discussion on these choices, we recommend referring to (57)(58)(59).…”

“…This considerably reduces the degrees of freedom needed to describe a specific system, as well as allowing a longer MD timestep to be used, both of which potentially increase simulation speeds by several orders of magnitude. Different levels of coarse graining, as well as the application of continuum models, are outlined in detail by Moquadam et al [ 52 ], and will be briefly discussed below.…”

Computational Approaches to Investigate and Design Lipid-binding Domains for Membrane Biosensing

“…[57,[59][60][61][62][63] However, in many instances, membrane binding takes place on timescales that are longer than those accessible to unbiased AA-MD simulations. [64] To address this limitation, techniques to enhance the sampling of this process have been put forward. Most notably, two techniques that have been used extensively for this purpose are (i) the highly mobile membrane-mimetic model (HMMM) [65] and (ii) coarse grain (CG) simulations.…”