Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly

Area of Science:

• Virology
• Biophysics
• Computational Biology

Background:

• HIV-1 maturation is critical for infectivity, involving capsid protein (CA) self-assembly into a protective shell.
• The precise mechanisms governing the initiation and early stages of HIV-1 capsid assembly are not fully understood.

Purpose of the Study:

• To investigate the mechanistic details of HIV-1 capsid assembly and disassembly using coarse-grained simulations.
• To explore the influence of CA concentration, molecular crowding, and CA conformational variability on capsid formation.

Main Methods:

• Coarse-grained molecular dynamics simulations were employed to model capsid assembly and disassembly.
• Simulations were conducted under various conditions, including different CA concentrations and molecular crowding levels.

Main Results:

• HIV-1 capsid assembly is a multi-stage process that relies on specific metastable intermediates for nucleation and growth.
• The formation of the mature capsid lattice is highly sensitive to environmental factors like CA concentration and molecular crowding.
• Subtle changes in these conditions can significantly alter self-assembly pathways and the resulting structural morphologies.

Conclusions:

• The study elucidates key mechanistic insights into HIV-1 capsid assembly, highlighting its complexity and sensitivity to cellular conditions.
• Findings provide a foundation for understanding viral maturation and could inform the design of novel antiviral therapies targeting capsid formation.