Sizes, conformational fluctuations, and SAXS profiles for intrinsically disordered proteins.

Area of Science:

• Biophysics
• Computational Biology
• Protein Science

Background:

• Intrinsically disordered proteins (IDPs) are abundant in eukaryotes and crucial for cellular functions through interactions with various molecules.
• Accurate characterization of IDP biophysical properties is essential for understanding their roles but remains challenging.
• Existing models often struggle to capture the dynamic and flexible nature of IDPs.

Purpose of the Study:

• To develop a transferable computational model for calculating the biophysical properties of intrinsically disordered proteins.
• To validate the model's predictions against experimental data from various biophysical techniques.
• To investigate the scaling behavior and conformational ensembles of IDPs.

Main Methods:

• Development of the transferable self-organized polymer (SOP-IDP) model.
• Simulation of various intrinsically disordered proteins using the SOP-IDP model.
• Comparison of simulated properties (radius of gyration, hydrodynamic radii, SAXS profiles) with experimental data (SAXS, FCS, PRE).

Main Results:

• SOP-IDP simulations showed excellent agreement with experimental radius of gyration (R^2=0.96) and hydrodynamic radii.
• Calculated SAXS profiles closely matched experimental data for 36 IDPs.
• IDPs globally follow Flory's scaling law, behaving as polymers in a good solvent, with sequence-specific features emerging from conformational analysis.

Conclusions:

• The transferable SOP-IDP model accurately predicts IDP biophysical properties, validating its utility.
• IDPs exhibit polymer-like behavior, with deviations explained by finite-size effects and sequence-specific conformational ensembles.
• The SOP-IDP model provides a foundation for studying IDP phase separation and interactions with nucleic acids.