Protein aggregates thermodynamically order regardless of sequence.

Area of Science:

• Biophysics
• Polymer Science
• Structural Biology

Background:

• Proteins can form either disordered aggregates or ordered assemblies like amyloid fibrils.
• These distinct phases have different roles in biological function and disease.
• The influence of protein sequence on phase preference remains poorly understood.

Purpose of the Study:

• To establish a statistical mechanical condition for the disorder-to-order transition in compact polymer aggregates, including proteins.
• To develop a universal equation predicting the favored phase based on sequence-dependent properties.

Main Methods:

• Developed a statistical mechanical theory for compact polymer aggregates.
• Calculated sequence-dependent energy variance using atomistic simulations.
• Validated the theory against experimental data for synthetic polymer crystallization.

Main Results:

• A universal equation predicts the favored phase (disordered vs. ordered) based on temperature, polymer length, and interaction energy variance.
• The theory accurately predicts experimental crystallization temperatures of synthetic polymers.
• Predicts that all aggregating protein sequences favor ordering, implying energy is needed to maintain disordered states.

Conclusions:

• Protein sequence critically determines the aggregation phase.
• The developed theory provides a parameter-free prediction of aggregation behavior.
• Suggests a general tendency for organic polymer aggregates to order on habitable planets.