Enhanced sampling for lipid-protein interactions during membrane dynamics

Abstract

The inflexible concept of membrane curvature as an independent property of lipid structures is today obsolete.Lipid bilayers behave as many-body entities with emergent properties that depend on their interactions with the environment. In particular, proteins exert crucial actions on lipid molecules that ultimately condition the collective properties of the membranes. In this review, the potential of enhanced molecular dynamics to address cell-biology problems is discussed. The cases of membrane deformation, membrane fusion, and the fusion pore are analyzed from the perspective of the dimensionality reduction by collective variables. Coupled lipid-protein interactions as fundamental determinants of large membrane remodeling events are also commented. Finally, novel strategies merging cell biology and physics are considered as future lines of research.

Intrinsic Disorder in α-Synuclein Regulates the Exocytotic Fusion Pore Transition

“…Intrinsically disordered regions in proteins that bind to the lipid bilayer add substantial complexity to the molecular description of the lipid–protein interplay in biological events, such as the nucleation of the fusion pore and its further expansion. , As pointed out by Uversky et al more than 20 years ago for α-synuclein, its extraordinary how a protein with an unstructured region is transformed into highly organized fibrils. Therefore, significant efforts have been made to improve computational modeling of intrinsically disordered proteins. − …”