Liaison amid disorder: non-native interactions may underpin long-range coupling in proteins

Area of Science:

• Protein structural biology
• Biophysics
• Computational biology

Background:

• Understanding protein behavior relies on characterizing residue interactions.
• Disordered conformational ensembles are increasingly recognized for their importance in protein function.
• Thermodynamic coupling between amino acid residues influences protein stability and dynamics.

Purpose of the Study:

• To investigate thermodynamic coupling between distant residues in globular proteins.
• To explore the role of non-native conformations in protein behavior.
• To contribute to the understanding of disordered conformational ensembles.

Main Methods:

• Utilized a lattice-model simulation approach.
• Analyzed double-mutant cycles to assess thermodynamic coupling.
• Studied interactions within non-native protein conformations.

Main Results:

• Demonstrated that interactions in non-native conformations can induce thermodynamic coupling between distant residues.
• Provided evidence for the significant role of disordered conformational ensembles in protein behavior.
• Quantified the coupling effects in a model protein system.

Conclusions:

• Non-native conformations are critical for understanding thermodynamic coupling in proteins.
• Disordered conformational ensembles play a crucial, often underestimated, role in protein dynamics and function.
• Lattice-model studies offer valuable insights into complex protein interactions.