MACV

MACV (Machupo Virus) is a tool that uses steered molecular dynamics (SMD) simulations to predict the effects of mutations on the binding affinity between two proteins, specifically the interaction between the MACV spike glycoprotein (GP1) and the human transferrin receptor (hTfR1). The method pulls the GP1 protein away from hTfR1 and uses the maximum applied force of separation and the area under the force-versus-distance curve as proxies for binding affinity. This approach provides insights into the GP1/hTfR1 interaction without requiring rigorous free energy calculations.

Key findings from using MACV include:

1. Differentiating between wild-type and mutant complexes without prior knowledge of the system.

2. Showing that the SMD scheme correlates well with relative free energy differences computed via free energy perturbation.

3. Identifying that one of the two large hydrogen-bonding networks in the GP1/hTfR1 interface may not be crucial for tight binding.

4. Suggesting that a critical viral site for infection may serve as an important evolutionary suppressor site for infection-resistant hTfR1 mutants.