Dissecting entropic coiling and poor solvent effects in protein collapse.

Area of Science:

• Biophysics
• Molecular Biology
• Computational Chemistry

Background:

• Protein folding and collapse are early events guided by protein elasticity.
• The roles of entropic coiling and hydrophobic forces in protein elastic response are not fully understood.

Purpose of the Study:

• To investigate the contributions of entropic coiling and hydrophobic forces to protein elasticity.
• To compare the elastic behavior of proteins with entropic chain models using molecular simulations.

Main Methods:

• Utilized molecular simulations to study stretched ubiquitin.
• Compared simulation results with models of proteins as entropic chains.
• Analyzed the effects of hydrophobic forces on protein persistence length.

Main Results:

• Discovered a high intrinsic stiffness of the protein backbone with a persistence length of 1.2 nm.
• Demonstrated that hydrophobic forces significantly reduce this stiffness to an apparent persistence length of 0.3-0.6 nm.
• Observed protein compaction beyond entropic coiling under poor solvent conditions (water).

Conclusions:

• Hydrophobic forces play a crucial role in determining the apparent elasticity of proteins in aqueous solutions.
• Protein softness observed in single-molecule experiments is largely due to hydrophobic interactions in water.
• The solvent environment significantly influences protein compaction and elastic properties.