Crowding effects on protein association: effect of interactions between crowding agents

Area of Science:

• Biophysics
• Computational Biology
• Chemical Physics

Background:

• The cellular cytoplasm is a crowded environment influencing biomolecular reactions.
• Theoretical models often use hard sphere crowding agents to study excluded volume effects.
• The impact of crowding agent interactions on protein association thermodynamics is less understood.

Purpose of the Study:

• To investigate the influence of crowding agent interactions on protein association thermodynamics.
• To compare the effects of hard sphere, interacting, and chain-like crowding agents.
• To determine the validity of the hard sphere model in complex cellular environments.

Main Methods:

• Computer simulations were employed to model protein association.
• Three types of crowding agents were simulated: hard spheres, spheres with interactions, and hard sphere chains.
• Protein association reactants and products were modeled as hard spheres.

Main Results:

• The excess free energy difference (nonideality factor) was largely insensitive to crowding agent interactions.
• This insensitivity was observed across different crowding agent types and was attributed to a cancellation of effects.
• Crowding effects were found to be sensitive to the shape of the protein association product.

Conclusions:

• The hard sphere model for crowding agents possesses a broad regime of validity for studying protein association thermodynamics.
• Simple hard sphere models are likely sufficient for qualitative understanding when non-excluded volume interactions are minor.
• This simplifies the theoretical approach to understanding crowding effects in cellular systems.