The contributions of surface charge and geometry to protein-solvent interaction

TL;DR

This study analyzes physical and geometrical properties of solvent-excluded surfaces in proteins, revealing universal negative surface charge, dipoles, and power-law relationships that influence protein-solvent interactions and folding.

Contribution

It uncovers the fundamental roles of surface charge and geometry in protein-solvent interactions, highlighting their importance over traditional hydrophobicity considerations.

Findings

All proteins have net negative surface charge and dipoles.

SES area and charge scale with protein size via power laws.

Surface charge correlates strongly with hydrophobicity and changes upon unfolding.

Abstract

To better understand protein-solvent interaction we have analyzed a variety of physical and geometrical properties of the solvent-excluded surfaces (SESs) over a large set of soluble proteins with crystal structures. We discover that all have net negative surface charges and permanent electric dipoles. Moreover both SES area and surface charge as well as several physical and geometrical properties defined by them change with protein size via well-fitted power laws. The relevance to protein-solvent interaction of these physical and geometrical properties is supported by strong correlations between them and known hydrophobicity scales and by their large changes upon protein unfolding. The universal existence of negative surface charge and dipole, the characteristic surface geometry and power laws reveal fundamental but distinct roles of surface charge and SES in protein-solvent interaction and make it possible to describe solvation and hydrophobic effect using theories on anion solute in protic solvent. In particular the great significance of surface charge for protein-solvent interaction suggests that a change of perception may be needed since from solvation perspective folding into a native state is to optimize surface negative charge rather than to minimize the hydrophobic surface area.