The Analytical Flory Random Coil Is a Simple-to-Use Reference Model for Unfolded and Disordered Proteins

Area of Science:

• Biophysics
• Computational Biology
• Polymer Physics

Background:

• Analytical polymer models describe unfolded proteins but often require user-defined parameters.
• Existing models lack a standardized reference state for comparing diverse experimental and simulation data.

Purpose of the Study:

• To develop a sequence-input, reference polymer model for unfolded proteins.
• To enable direct comparison and normalization of experimental and simulation results for disordered proteins.

Main Methods:

• Utilized all-atom simulations of polypeptides and polymer scaling theory.
• Parameterized an analytical model, the analytical Flory random coil (AFRC), for ideal chains (ν = 0.50).
• Validated the model by identifying intramolecular interactions and contextualizing experimental radii of gyration.

Main Results:

• The analytical Flory random coil (AFRC) model requires only the amino acid sequence as input.
• AFRC provides direct access to conformational order parameter distributions.
• Successfully identified sequence-specific interactions and contextualized experimental data for disordered proteins.

Conclusions:

• The analytical Flory random coil (AFRC) offers a user-friendly reference polymer model for unfolded proteins.
• AFRC aids in interpreting experimental and simulation data by providing a standardized comparison framework.
• The model is available as a software package and Google Colab notebook.