Dimension conversion and scaling of disordered protein chains.

Area of Science:

• Biophysics
• Computational Biology
• Protein Dynamics

Background:

• Single-molecule fluorescence resonance energy transfer (smFRET) spectroscopy is crucial for determining protein dimensions and energetics.
• Accurate interpretation of smFRET data requires understanding the relationship between radius of gyration (Rg) and end-to-end distance (Ree).
• Disordered proteins present unique conformational challenges for structural analysis.

Purpose of the Study:

• To establish a robust correlation between Rg and Ree for disordered protein conformational ensembles.
• To develop an improved method for analyzing smFRET data by refining the conversion formula.
• To investigate the scaling laws governing coil-globule transitions in proteins and identify finite-size effects.

Main Methods:

• Coarse-grained molecular dynamics simulations were employed to generate conformational ensembles of denatured and intrinsically disordered proteins.
• Analysis of the relationship between Rg and Ree distributions under varying solvent conditions.
• Testing and validation of a modified conversion formula for smFRET data analysis.
• Examination of scaling laws during coil-globule transitions and evaluation of the Sanchez chain model.

Main Results:

• An excellent linear correlation was observed between average Rg and Ree for disordered protein chains of fixed length, deviating from Gaussian chain predictions.
• A modified conversion formula was proposed, significantly reducing discrepancies between smFRET and small-angle X-ray scattering (SAXS) data.
• Significant finite-size effects were revealed during coil-globule transitions, with scaling exponents potentially exceeding theoretical boundaries.
• The mean-field approximation of the Sanchez chain model demonstrated effectiveness for expanded protein chains.

Conclusions:

• The developed method provides a more accurate way to extract protein dimension and energetics information from smFRET data, particularly for disordered systems.
• The findings offer insights into the conformational behavior of disordered proteins and the physics of coil-globule transitions.
• The study highlights the importance of considering finite-size effects and refining theoretical models for accurate protein structural analysis.