Computational Modeling of Realistic Cell Membranes

Marrink, Siewert J.

doi:10.1016/j.bpj.2017.11.2032

Cited by 101 publications

(145 citation statements)

References 0 publications

Supporting

Mentioning

141

Contrasting

Order By: Relevance

“…Molecular dynamics (MD) simulations enable investigation of both protein-lipid interactions (31) and the larger-scale organization of complex cell membranes (32). Simulations of PH domains have been used to explore the structure (18,33), dynamic mechanisms (20,24,26,30), and energetics (34,35) of PH domain/membrane interactions.…”

Section: Introductionmentioning

confidence: 99%

Multiple lipid binding sites determine the affinity of PH domains for phosphoinositide-containing membranes

et al. 2020

View full text Add to dashboard Cite

Association of peripheral proteins with lipid bilayers regulates membrane signaling and dynamics. Pleckstrin homology (PH) domains bind to phosphatidylinositol phosphate (PIP) molecules in membranes. The effects of local PIP enrichment on the interaction of PH domains with membranes is unclear. Molecular dynamics simulations allow estimation of the binding energy of GRP1 PH domain to PIP3-containing membranes. The free energy of interaction of the PH domain with more than two PIP3 molecules is comparable to experimental values, suggesting that PH domain binding involves local clustering of PIP molecules within membranes. We describe a mechanism of PH binding proceeding via an encounter state to two bound states which differ in the orientation of the protein relative to the membrane, these orientations depending on the local PIP concentration. These results suggest that nanoscale clustering of PIP molecules can control the strength and orientation of PH domain interaction in a concentration-dependent manner.

show abstract

Section: Introductionmentioning

confidence: 99%

Multiple lipid binding sites determine the affinity of PH domains for phosphoinositide-containing membranes

et al. 2020

View full text Add to dashboard Cite

show abstract

“…6). There is also an increasing understanding of the complexity of lipid membranes, the diversity of such complexity, and the impact this lipid complexity has on membrane function, particularly on protein-lipid interactions (7)(8)(9).…”

mentioning

confidence: 99%

Defining how multiple lipid species interact with inward rectifier potassium (Kir2) channels

Duncan

Corey

Sansom

2020

Proc. Natl. Acad. Sci. U.S.A.

118

View full text Add to dashboard Cite

Protein–lipid interactions are a key element of the function of many integral membrane proteins. These potential interactions should be considered alongside the complexity and diversity of membrane lipid composition. Inward rectifier potassium channel (Kir) Kir2.2 has multiple interactions with plasma membrane lipids: Phosphatidylinositol (4, 5)-bisphosphate (PIP2) activates the channel; a secondary anionic lipid site has been identified, which augments the activation by PIP2; and cholesterol inhibits the channel. Molecular dynamics simulations are used to characterize in molecular detail the protein–lipid interactions of Kir2.2 in a model of the complex plasma membrane. Kir2.2 has been simulated with multiple, functionally important lipid species. From our simulations we show that PIP2interacts most tightly at the crystallographic interaction sites, outcompeting other lipid species at this site. Phosphatidylserine (PS) interacts at the previously identified secondary anionic lipid interaction site, in a PIP2concentration-dependent manner. There is interplay between these anionic lipids: PS interactions are diminished when PIP2is not present in the membrane, underlining the need to consider multiple lipid species when investigating protein–lipid interactions.

show abstract

“…To understand the toppling process at the molecular level, and to investigate a possible role of lipid composition, molecular dynamics (MD) simulations are a suitable tool [16][17][18][19] . In particular coarse-grained (CG) models have proven their efficiency to simulate inherently slow processes such as reorientation of membrane proteins and identification of protein-lipid-binding sites 20 .…”

mentioning

confidence: 99%

Membrane mediated toppling mechanism of the folate energy coupling factor transporter

et al. 2020

Self Cite

View full text Add to dashboard Cite

Energy coupling factor (ECF) transporters are responsible for the uptake of micronutrients in bacteria and archaea. They consist of an integral membrane unit, the S-component, and a tripartite ECF module. It has been proposed that the S-component mediates the substrate transport by toppling over in the membrane when docking onto an ECF module. Here, we present multi-scale molecular dynamics simulations and in vitro experiments to study the molecular toppling mechanism of the S-component of a folate-specific ECF transporter. Simulations reveal a strong bending of the membrane around the ECF module that provides a driving force for toppling of the S-component. The stability of the toppled state depends on the presence of non-bilayer forming lipids, as confirmed by folate transport activity measurements. Together, our data provide evidence for a lipid-dependent toppling-based mechanism for the folate-specific ECF transporter, a mechanism that might apply to other ECF transporters.

show abstract

Computational Modeling of Realistic Cell Membranes

Cited by 101 publications

References 0 publications

Multiple lipid binding sites determine the affinity of PH domains for phosphoinositide-containing membranes

Multiple lipid binding sites determine the affinity of PH domains for phosphoinositide-containing membranes

Defining how multiple lipid species interact with inward rectifier potassium (Kir2) channels

Membrane mediated toppling mechanism of the folate energy coupling factor transporter

Contact Info

Product

Resources

About