Hydrodynamic Radii of Intrinsically Disordered Proteins: Fast Prediction by Minimum Dissipation Approximation and...

Area of Science:

• Biophysics
• Computational Biology
• Protein Dynamics

Background:

• Diffusion coefficients of globular and unfolded proteins are predictable by mass or chain length.
• This predictive accuracy falters for intrinsically disordered proteins (IDPs) with structural domains.

Purpose of the Study:

• To develop a rapid and accurate predictive methodology for estimating the diffusion coefficients of intrinsically disordered proteins (IDPs).
• To improve the prediction of hydrodynamic properties for both fully unstructured and multidomain disordered proteins.

Main Methods:

• Utilized accelerated conformational sampling via self-avoiding random walks.
• Incorporated hydrodynamic interactions between coarse-grained protein subunits using the generalized Rotne-Prager-Yamakawa approximation.
• Employed the minimum dissipation approximation to estimate the hydrodynamic radius.

Main Results:

• The proposed methodology demonstrated higher accuracy in predicting hydrodynamic radii compared to the Kirkwood approximation and phenomenological approaches.
• Validated predictions against a large dataset of experimentally measured hydrodynamic radii for IDPs across various chain lengths and domain compositions.
• The method effectively accounts for the complexities introduced by structural domains in IDPs.

Conclusions:

• The developed technique offers a more accurate approach to predicting diffusion coefficients for intrinsically disordered proteins.
• This methodology holds significant potential for advancing the understanding and prediction of hydrodynamic properties in disordered proteins.
• The findings may aid in the characterization of IDPs in biological systems.