Characterizing conformation changes in proteins through the torsional elastic response.

Area of Science:

• Protein dynamics and biophysics
• Computational biology
• Molecular evolution

Background:

• Understanding protein function requires knowledge of their dynamic behavior.
• Existing models for protein conformation changes include conformational selection and induced fit.
• The Torsional Network Model (TNM) offers a new perspective in torsion angle space.

Purpose of the Study:

• To investigate the relationship between protein thermal dynamics and functional conformation changes.
• To test a null model for random conformation changes against observed protein dynamics.
• To reconcile distinct models of protein conformation changes within a unified framework.

Main Methods:

• Utilized the Torsional Network Model (TNM) to analyze protein dynamics.
• Developed and applied a null model comparing normal mode contributions to conformation changes and thermal fluctuations.
• Analyzed deviations from the null model to identify selected conformation changes.

Main Results:

• Deviations from the null model were generally small, indicating protein dynamics align with thermal fluctuations.
• Significant deviations revealed conformation changes driven by few low-frequency normal modes and small energy barriers.
• Selected conformation changes were frequently linked to ligand binding, especially phosphorylation.

Conclusions:

• Protein intrinsic dynamics, influenced by natural selection, are consistent with functional conformation changes.
• The TNM framework unifies conformational selection and induced fit models by linking thermal and functional dynamics.
• This study highlights the crucial role of protein plasticity in allostery, evolution, and self-assembly.