#22 · Structural bio & protein design

MD simulations map lipid-dependent allosteric coupling in membrane signaling complexes

The dominant thread across these items is molecular simulation used to map how allosteric communication and lipid engagement are organized in membrane-associated signaling proteins. A multi-replica 1 µs all-atom study of Plexin-B1–Rap1b complexes on PIP2/PIP3 membranes reports lipid-dependent shifts in allosteric communication networks. MARTINI coarse-grained simulations of eight Ca2+-sensing synaptotagmin C2 domains attribute PIP2 binding to loop net charge, with local aromatic residues governing membrane penetration. A protein frustration analysis of GPCR:G protein complexes identifies orthosteric and allosteric active sites. What is new is the explicit treatment of lipid composition as a modulator of allosteric coupling in membrane-anchored complexes, which the Plexin-B1 study addresses directly; the synaptotagmin and GPCR items address lipid engagement and site identification rather than coupling per se.