Protein collapse is encoded in the folded state architecture.

Area of Science:

• Protein biophysics
• Computational biology
• Structural biology

Background:

• Globular proteins exhibit high packing density in folded states.
• Protein radius of gyration (Rg) scales with N^ν, with ν ≈ 1/3 for folded and ν ≈ 0.6 for unfolded states.
• The collapsibility of unfolded proteins under native-like conditions remains poorly understood.

Purpose of the Study:

• To develop a theory for quantitatively assessing protein collapsibility using contact maps.
• To investigate the dependence of collapsibility on protein architecture and length.
• To provide insights into protein size, domain evolution, and RNA molecule compactness.

Main Methods:

• Developed a theoretical framework utilizing protein contact maps.
• Applied the theory to analyze over two thousand protein structures.
• Performed simulations to validate theoretical predictions.

Main Results:

• Protein collapsibility is universal but influenced by native structure and protein architecture.
• Beta-sheet proteins demonstrate significantly higher collapsibility compared to alpha-helical proteins.
• The theory explains the size limitations of single-domain proteins and the emergence of multi-domain proteins.

Conclusions:

• Collapsibility is a key factor in determining protein size and domain organization.
• The findings support the