Prediction of stability changes upon mutation in an icosahedral capsid

Area of Science:

• Biophysics
• Structural Biology
• Computational Biology

Background:

• Thermodynamic stability of viral capsids is crucial for their function and assembly.
• Understanding capsid stability informs the design of novel nanomaterials and drug delivery systems.

Purpose of the Study:

• To computationally assess the impact of mutations on the thermodynamic stability of a T=1 icosahedral capsid.
• To validate a simulation method against experimental data on capsid formation.

Main Methods:

• Simulating a single pentamer of lumazine synthase from Aquifex aeolicus with imposed crystal symmetry to model an infinite lattice of capsids.
• Estimating the free energy of association using an empirical method to quantify capsid stability.
• Investigating the effects of seven specific mutations on capsid stability.

Main Results:

• The simulation approach accurately predicted the effect of six out of seven mutations on capsid stability.
• The method successfully identified critical interaction networks responsible for capsid assembly.
• The study highlighted the inherent plasticity of subunit interfaces within the capsid.

Conclusions:

• Computational simulation is a reliable method for predicting mutation effects on capsid stability.
• The identified interaction networks provide insights into the mechanisms of capsid assembly.
• The plasticity of interfaces suggests adaptability in capsid structures.