Capturing the multiscale dynamics of membrane protein complexes with all-atom, mixed-resolution, and coarse-grained...

Area of Science:

• Biophysics
• Computational Biology
• Structural Biology

Background:

• Modeling protein complex structures and dynamics in biological membranes presents significant challenges.
• Heterogeneous environments like lipid bilayers require advanced simulation techniques.

Purpose of the Study:

• To develop cost-effective computational models for simulating membrane protein complexes.
• To investigate the structures and dynamics of G protein-coupled receptors (GPCRs) in lipid bilayers.
• To elucidate the regulatory role of intracellular loops in GPCR function.

Main Methods:

• Utilized all-atom, mixed-resolution, and coarse-grained simulation models.
• Simulated five complex models of two distinct GPCRs in a lipid-bilayer membrane.
• Performed simulations on the nanosecond (ns) to microsecond (μs) timescales.

Main Results:

• Observed consistent structural stability across different model resolutions.
• Identified a swinging motion of an intracellular loop, providing molecular details of its regulatory role.
• Mixed-resolution and coarse-grained models exhibited 2x and 4x faster protein diffusion, respectively.
• Achieved 4-fold and 400-fold speed-ups in simulation performance with reduced-resolution models.

Conclusions:

• Combining all-atom with reduced-resolution models offers an efficient approach for simulating complex membrane protein systems.
• This study provides a guide for simulating challenging systems in heterogeneous environments.
• The developed models offer insights into GPCR regulation and dynamics.