Shape-Aware Diffusivity of DNA Binding Proteins Undergoing Rotation-Coupled Sliding Dynamics along DNA.

Area of Science:

• Biophysics
• Computational Biology
• Molecular Dynamics

Background:

• DNA-binding proteins locate targets via rotation-coupled sliding.
• The classical Bagchi-Blainey-Xie (BBX) model uses spherical approximations for proteins.
• Existing models lack detailed structural incorporation for accurate hydrodynamic predictions.

Purpose of the Study:

• To introduce BBXB, a shape-aware hydrodynamic model for DNA-protein sliding.
• To improve prediction accuracy by incorporating 3D protein structure and anisotropy.
• To establish a parameter-free framework linking molecular shape to sliding dynamics.

Main Methods:

• Derived translational and rotational frictions from 3D protein structures using Happel-Brenner integrals.
• Incorporated a roughness parameter for protein-DNA interaction energy landscapes.
• Validated BBXB against experimental diffusion coefficients and hydrodynamic benchmarks for diverse DNA-binding proteins.

Main Results:

• BBXB accurately reproduces experimental diffusion coefficients for Lac repressor and hOgg1 glycosylase.
• BBXB predictions correlate strongly (R² ≈ 0.99) with SoMo/GRPY benchmarks across 27 proteins.
• Rotational drag was identified as the dominant dissipation factor, increasing with shape anisotropy and DNA offset.

Conclusions:

• BBXB provides a predictive, parameter-free hydrodynamic model for DNA-protein sliding.
• Molecular shape and anisotropy are critical determinants of 1D sliding dynamics.
• The model quantitatively links protein structure to biophysical sliding mechanisms.