Tabulation as a high-resolution alternative to coarse-graining protein interactions: Initial application to virus...

Area of Science:

• Computational chemistry and biophysics.
• Development of novel simulation methodologies.

Background:

• Traditional coarse-graining methods often compromise chemical accuracy.
• Simulating large macromolecular systems requires efficient computational strategies.

Purpose of the Study:

• To present an energy tabulation strategy for simulating large systems of interacting macromolecules.
• To improve computational efficiency and accuracy in molecular simulations.

Main Methods:

• Applied an energy tabulation strategy to proteins treated as rigid bodies.
• Constructed distance and orientation-dependent interaction energy tables.
• Utilized a simple alpha-carbon Gō-like model for hepatitis B viral capsid subunit interactions.
• Combined energy tabulation with the weighted ensemble (WE) method for enhanced sampling.

Main Results:

• Achieved simulation speed increases of up to 6700-fold compared to simulations without tabulation.
• Maintained minimal loss in accuracy.
• The weighted ensemble method yielded pathways for the final ~25% of the viral capsid assembly process.

Conclusions:

• Energy tabulation offers a significant speed enhancement for simulating large macromolecular systems.
• This method provides a more structurally realistic model for viral capsid assembly studies.
• Combining tabulation with WE methods further improves sampling efficiency for complex biological processes.