Redox Entropy of Plastocyanin: Developing a Microscopic View of Mesoscopic Polar Solvation

TL;DR

This study combines analytical formalisms and MD simulations to better understand the mesoscopic polar solvation and redox entropy of plastocyanin in water, highlighting limitations of continuum models and the importance of interface structure.

Contribution

It develops a microscopic formalism for polar solvation at the mesoscopic scale and compares it with MD simulations, revealing the need to incorporate realistic interfacial water density profiles.

Findings

Continuum models underestimate solvation entropies.

Microscopic calculations align better with MD simulations.

Protein-water interface structure significantly affects solvation properties.

Abstract

We report applications of analytical formalisms and Molecular Dynamics (MD) simulations to the calculation of redox entropy of plastocyanin metalloprotein in aqueous solution. The goal of our analysis is to establish critical components of the theory required to describe polar solvation at the mesoscopic scale. The analytical techniques include a microscopic formalism based on structure factors of the solvent dipolar orientations and density and continuum dielectric theories. The microscopic theory employs the atomistic structure of the protein with force-field atomic charges and solvent structure factors obtained from separate MD simulations of the homogeneous solvent. The MD simulations provide linear response solvation free energies and reorganization energies of electron transfer in the temperature range 280--310 K. We found that continuum models universally underestimate solvation entropies, and a more favorable agreement is reported between the microscopic calculations and MD simulations. The analysis of simulations also suggests that difficulties of extending standard formalisms to protein solvation are related to the inhomogeneous structure of the solvation shell at the protein-water interface combining islands of highly structured water around ionized residues along with partial dewetting of hydrophobic patches. Quantitative theories of electrostatic protein hydration need to incorporate realistic density profile of water at the protein-water interface.