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

## TL;DR

This study uses simulations to explore how HIV-1 capsids form and disassemble, revealing that the process involves multiple stages and is sensitive to environmental conditions.

## Contribution

The paper introduces coarse-grained simulations to study HIV-1 capsid self-assembly and disassembly under varying conditions.

## Key findings

- Capsid nucleation and growth involve metastable intermediates.
- Local conditions like CA concentration and molecular crowding significantly affect assembly.
- Subtle environmental changes influence the structural morphologies of the capsid.

## Abstract

The maturation of HIV-1 viral particles is essential for viral infectivity. During maturation, many copies of the capsid protein (CA) self-assemble into a capsid shell to enclose the viral RNA. The mechanistic details of the initiation and early stages of capsid assembly remain to be delineated. We present coarse-grained simulations of capsid assembly under various conditions, considering not only capsid lattice self-assembly but also the potential disassembly of capsid upon delivery to the cytoplasm of a target cell. The effects of CA concentration, molecular crowding, and the conformational variability of CA are described, with results indicating that capsid nucleation and growth is a multi-stage process requiring well-defined metastable intermediates. Generation of the mature capsid lattice is sensitive to local conditions, with relatively subtle changes in CA concentration and molecular crowding influencing self-assembly and the ensemble of structural morphologies.