Capturing the multiscale dynamics of membrane protein complexes with all-atom, mixed-resolution, and coarse-grained models.
The structures and dynamics of protein complexes are often challenging to model in heterogeneous environments such as biological membranes. Herein, we meet this fundamental challenge at attainable cost with all-atom, mixed-resolution, and coarse-grained models of vital membrane proteins. We systematically simulated five complex models formed by two distinct G protein-coupled receptors (GPCRs) in the lipid-bilayer membrane on the ns-to-μs timescales. These models, which suggest the swinging motion of an intracellular loop, for the first time, provide the molecular details for the regulatory role of such a loop. For the models at different resolutions, we observed consistent structural stability but various levels of speed-ups in protein dynamics. The mixed-resolution and coarse-grained models show two and four times faster protein diffusion than the all-atom models, in addition to a 4- and 400-fold speed-up in the simulation performance. Furthermore, by elucidating the strengths and challenges of combining all-atom models with reduced resolution models, this study can serve as a guide to simulating other complex systems in heterogeneous environments efficiently.
Department of Chemistry, The University of Vermont, Burlington, VT 05405, USA. jianing.li@uvm.edu.
Chenyi
C
Liao
Department of Chemistry, The University of Vermont, Burlington, VT 05405, USA. jianing.li@uvm.edu.
Xiaochuan
X
Zhao
Department of Chemistry, The University of Vermont, Burlington, VT 05405, USA. jianing.li@uvm.edu.
Jiyuan
J
Liu
Department of Chemistry, The University of Vermont, Burlington, VT 05405, USA. jianing.li@uvm.edu.
Severin T
ST
Schneebeli
Schrödinger, Inc., 101 SW Main Street, Suite 1300, Portland, OR 97204, USA.
John C
JC
Shelley
Department of Chemistry, The University of Vermont, Burlington, VT 05405, USA. jianing.li@uvm.edu.
Jianing
http://orcid.org/0000-0002-0143-8894
J
Li
D002462:Cell Membrane / Q000502:physiology; D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation
D008051:Lipid Bilayers; D008565:Membrane Proteins