Disease-related protein-protein interactions are important molecular targets for drug discovery campaigns. The dynamics of a disordered loop, which are commonly found in the receptor binding domain of many proteins, often plays a decisive role during protein-protein or protein-small molecule binding events. One notable example is the interactions between two proteins from Plasmodium falciparum, PfAMA1-PfRON2, which are crucial for the malaria parasite's invasion into human red blood cells. A thorough understanding of the interactions between these macromolecular binding partners is important for designing better therapeutics against this ancient disease. The available crystal structures of the PfAMA1-PfRON2 complex show insufficient electron density, making it challenging to fully understand the molecular-level association of the domain II (DII) loop with the PfRON2. To address this, we have computationally simulated the dynamics and free energetics of DII loop closing processes, identifying a set of key amino acid residues in the PfRON2 helix that are essential for binding. The subsequent experimental validation of the relative importance of residues in context provides a comprehensive understanding of the molecular recognition event between PfAMA1 and PfRON2, specifically in the post-binding stage. This insight could potentially open up new avenues to drug discovery against malaria.