We investigate the structural organization of cholesterol (CHOL) analogues in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayers using coarse-grained molecular dynamics simulations and the MARTINI forcefield. Different sterol molecules are modelled by increasing (CHOLL) or decreasing (CHOLS) the diameter of the sterol beads employed in the MARTINI model of CHOL. At high sterol concentrations, (x sterol = 0.5), typical of liquid ordered phases, we find that the sterol arrangement and sterol-DPPC interactions strongly depend on the sterol size. Smaller sterols (CHOLS and CHOL) form linear clusters, while the larger sterols (CHOLL) arrange themselves into disc shaped clusters. By combining structural and dynamical properties we also investigate the S o → L d transition for the CHOLL and CHOLS sterols. We show that small changes in the sterol size significantly affect the stability of the gel phase with the gel phase stabilized by the small sterols, but destabilized by large sterols. The general dependence of the phase behaviour of the membrane with sterol content, is reminiscent of the one observed in naturally occurring membranes. The relevance of our results to understand current cholesterol-bilayer structural models is discussed.
In this chapter, we discuss the application of molecular dynamics computer simulation to investigate biological molecules. Starting with the basics of molecular dynamics we discuss state-of-the-art force fields for biomolecular simulations, advanced simulation techniques for enhanced sampling, computation of free energies, investigation of rare events, and quantification of elastic properties of biological membranes. A critical discussion of current opportunities in the development of integrated experimental and simulation approaches in the area of NMR and scattering techniques is provided. We close the chapter with an overview of future directions for biomolecular simulations, and how these directions can build on our current ability to perform very large simulations of, for example, organelles and viruses.
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.