Specific Interactions and Environment Flexibility Tune Protein Stability under Extreme Crowding

Macromolecular crowding influences protein mobility and stability in vivo. A precise description of the effect on thermal requires estimate combined effects excluded volume, specific protein-environment interactions, as well response crowders. Here, we explore an ideal model system, lysozyme powder state, to dissect factors controlling melting under extreme crowding. By deploying state-of-the art molecular simulations, supported by calorimetric experiments, assess role environment flexibility intermolecular electrostatic interactions. In particular, show that temperature-dependent macromolecular crowders, along with significantly alleviates stabilizing contributions static volume effect.