A Sequence-Specific Theory for Charge-Regulating IDPs

Area of Science:

• Biophysics
• Computational Biology
• Polymer Physics

Background:

• Intrinsically disordered proteins (IDPs) lack stable 3D structures, making their behavior complex.
• Charge regulation from acidic/basic residues is crucial for IDP function but often overlooked in theories.
• Understanding IDP sequence-structure-charge relationships is key to their biological roles.

Purpose of the Study:

• To develop a theoretical framework for describing charge regulation and conformational changes in intrinsically disordered proteins.
• To investigate how amino acid sequence influences the ionization states and physical properties of IDPs.
• To provide a method for predicting IDP behavior based on their amino acid sequence.

Main Methods:

• Utilized the Edwards-Singh variational method to create an approximate theory for IDPs.
• Derived coupled algebraic equations for renormalized Kuhn length and residue-specific mean-fields.
• Developed a numerical scheme to solve these equations and applied them to model systems.

Main Results:

• The theory successfully predicts sequence-dependent charge regulation and conformational changes in IDPs.
• Demonstrated suppressed ionization due to electrostatics and enhanced ionization at chain ends for weak polyelectrolytes.
• Showcased distinct ionization behaviors for well-mixed versus blocky sequences of (EK)25, impacting net charge and swelling.

Conclusions:

• The developed theory accurately captures the interplay between sequence, charge regulation, and conformation in intrinsically disordered proteins.
• Sequence composition significantly impacts the ionization state and physical properties of IDPs across different pH values.
• This work provides a valuable tool for predicting and understanding the behavior of intrinsically disordered proteins.