Evaluation of Essential Dynamics and Fixed-Length Coarse Graining for Multidomain Proteins

Area of Science:

• Biomolecular modeling
• Computational biophysics
• Protein dynamics

Background:

• All-atom (AA) models are computationally intensive for large biomolecules.
• Coarse-grained (CG) models offer a way to simulate larger scales.
• Multidomain proteins (MDPs) present unique challenges for CG modeling.

Purpose of the Study:

• To evaluate Essential Dynamics Coarse Graining (EDCG) and Fixed-Length Coarse Graining (FLCG) for MDPs.
• To assess the ability of FLCG to preserve protein dynamics.
• To demonstrate FLCG's versatility in various applications.

Main Methods:

• Investigated EDCG and FLCG for MDPs with 1-10 residues/CG site.
• Studied 13 diverse MDPs.
• Applied FLCG to a class B G-protein-coupled receptor.
• Demonstrated progressive backmapping from low to high resolution.

Main Results:

• Both EDCG and FLCG successfully preserved MDP dynamics.
• FLCG proved to be an excellent approximation of EDCG and a simpler approach.
• FLCG showed agreement with experimental data for a GPCR.
• Progressive backmapping successfully recovered higher-resolution models from lower-resolution ones.

Conclusions:

• FLCG is a robust and straightforward method for constructing highly coarse-grained MDP models.
• FLCG demonstrates broad applicability for complex biomolecules in multiscale simulations.
• FLCG facilitates the recovery of detailed information from coarse-grained representations.