Solvated dissipative electro-elastic network model of hydrated proteins

Area of Science:

• Biophysics
• Computational Biology
• Protein Dynamics

Background:

• Elastic network models (ENMs) simplify protein structures into networks of residues connected by springs.
• Existing ENMs often lack detailed treatment of solvent effects, particularly hydration of surface residues.

Purpose of the Study:

• To develop an enhanced ENM that accounts for protein surface hydration and its impact on protein dynamics and function.
• To investigate how solvation influences electrostatic properties, dielectric response, and allosteric regulation in proteins.

Main Methods:

• Incorporation of dissipative dynamics using overdamped Langevin equations for normal-mode vibrations.
• Modeling protein surface heterogeneity and softening due to hydration of ionized residues.
• Formulation of response functions for electrostatic potential, electric field, and dielectric properties.

Main Results:

• Solvation introduces diagonal terms that soften spring constants and off-diagonal dipole-dipole terms that correlate residue displacements.
• A slow dielectric relaxation peak, two orders of magnitude slower than the main protein relaxation, emerges due to surface residue solvation.
• While global ion binding thermodynamics are minimally affected, solvation dramatically enhances protein conformational changes upon active site charge perturbation.

Conclusions:

• The enhanced ENM provides a more realistic representation of protein dynamics by including hydration effects.
• Solvation plays a crucial role in modulating protein allostery, particularly in response to changes at the active site.
• The model offers insights into redox reactions, spectroscopy, and protein conformational dynamics.