Phosphoinositides are a family of membrane phospholipids that play crucial roles in membrane regulatory events. As such, these lipids are often a key part of molecular dynamics simulation studies of biological membranes, in particular of those employing coarse-grain models because of the potential long times and sizes of the involved membrane processes. Version 3 of the widely used Martini coarse-grain force field has been recently published, greatly refining many aspects of biomolecular interactions. In order to properly use it for lipid membrane simulations with phosphoinositides, we put forth the Martini 3-specific parameterization of inositol, phosphatidylinositol, and seven physiologically relevant phosphorylated derivatives of phosphatidylinositol. Compared to parameterizations for earlier Martini versions, focus was put on a more accurate reproduction of the behavior seen in both atomistic simulations and experimental studies, including the signaling-relevant phosphoinositide interaction with divalent cations. The models that we develop improve upon the conformational dynamics of phosphoinositides in the Martini force field and provide stable topologies at typical Martini time steps. They are able to reproduce experimentally known protein-binding poses as well as phosphoinositide aggregation tendencies. The latter was tested both in the presence and absence of calcium and included correct behavior of PI(4,5)P2 calcium-induced clusters, which can be of relevance for regulation.
Phosphatidylinositol 4,5- bisphosphate (PI(4,5)P2) is a minor but ubiquitous component of the inner leaflet of the plasma membrane of eukaryotic cells. However, due to its particular complex biophysical properties, it stands out from its neighboring lipids as one of the most important regulators of membrane-associated signaling events. Despite its very low steady-state concentration, PI(4,5)P2 is able to engage in a multitude of simultaneous cellular functions that are temporally and spatially regulated through the presence of localized transient pools of PI(4,5)P2 in the membrane. These pools are crucial for the recruitment, activation, and organization of signaling proteins and consequent regulation of downstream signaling. The present review showcases some of the most important PI(4,5)P2 molecular and biophysical properties as well as their impact on its membrane dynamics, lateral organization, and interactions with other biochemical partners.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.