Emergent Effect of Mixed Crowders on Protein Dimerization

Area of Science:

• Biophysics
• Computational Biology
• Protein Science

Background:

• In vivo protein associations are influenced by cellular crowding, a complex phenomenon difficult to replicate experimentally.
• Current methods using homogeneous crowders offer limited insights into actual cellular conditions.

Purpose of the Study:

• To develop a minimalistic coarse-grained model for GB1 dimerization under crowding conditions.
• To investigate the impact of single and mixed crowder species on protein dimerization stability.

Main Methods:

• A coarse-grained model was developed using effective potential parameters from high-resolution Martini simulations.
• The model was applied to study GB1 dimerization in the presence of lysozyme crowders and binary crowder mixtures.
• Analysis focused on the balance between enthalpy and entropy contributions to stability.

Main Results:

• GB1 dimerization was destabilized by lysozyme crowders, consistent with experimental observations.
• Binary crowder mixtures showed variable effects on dimerization stability, depending on mixing conditions and volume fraction.
• Smaller crowder species dominated the effects in mixtures of different-sized crowders.

Conclusions:

• The study provides a model to understand crowding effects on protein dimerization.
• Crowding's influence on protein stability is a complex interplay of enthalpy and entropy, not predictable from single crowder properties.
• Results offer insights for interpreting experiments under simulated cellular conditions.