Thermally induced structural organization of nanodiscs by coarse-grained molecular dynamics simulations

Membrane scaffold proteins (MSP) nanodiscs have been extensively used in structural study of membrane proteins. In cryo-EM, an incorporation of target proteins into nanodiscs is conducted under a rapid change from cryogenic to ambient temperatures. We present a coarse-grained molecular dynamics (CGMD) study for investigating an effect of temperature on the structural organization of DPPC-nanodisc and POPC-nanodisc. A non-monotonic response of physical quantities (i.e. the lipid order parameter, nanodisc flatness, structural change, solvation property, radius of gyration) with increase in temperature (T = 200–350 K) is found to be associated with the gel-ripple-liquid crystalline phase change within nanodiscs. The reorganization of lipids upon temperature variation induced conformational changes of MSP to minimize hydrophobic exposure of the lipid membrane to an aqueous environment. Structural response to temperature is different to a certain extent between the saturated DPPC and unsaturated POPC. [Display omitted] •Structural reorganization of nanodiscs is associated with a physical state change.•A phase change of lipid bilayers induces conformational changes of MSP.•A change from discoidal to corrugated structure was observed as temperature rises.•Nanodiscs with saturated DPPC are more resistant to structural change than unsaturated POPC.