Characterizing hydrophobicity of amino acid side chains in a protein environment via measuring contact angle of a water nanodroplet on planar peptide network

Abstract

Hydrophobicity of macroscopic planar surface is conventionally characterized by the contact angle of water droplets. However, this engineering measurement cannot be directly extended to surfaces of proteins, due to the nanometer scale of amino acids and inherent nonplanar structures. To measure the hydrophobicity of side chains of proteins quantitatively, numerous parameters were developed to characterize behavior of hydrophobic solvation. However, consistency among these parameters is not always apparent. Herein, we demonstrate an alternative way of characterizing hydrophobicity of amino acid side chains in a protein environment by constructing a monolayer of amino acids (i.e., artificial planar peptide network) according to the primary and the β-sheet secondary structures of protein so that the conventional engineering measurement of the contact angle of a water droplet can be brought to bear. Using molecular dynamics simulations, contact angles θ of a water nanodroplet on the planar peptide network, together with excess chemical potentials of purely repulsive methane-sized Weeks−Chandler−Andersen solute, are computed. All of the 20 types of amino acids and the corresponding planar peptide networks are studied. Expectedly, all of the planar peptide networks with nonpolar amino acids are hydrophobic due to θ > 90°, whereas all of the planar peptide networks of the polar and charged amino acids are hydrophilic due to θ < 90°. Planar peptide networks of the charged amino acids exhibit complete-wetting behavior due to θ = 0°. This computational approach for characterization of hydrophobicity can be extended to artificial planar networks of other soft matter.hydrophobicity | amino acids | contact angle | nanodroplet | water H ydrophobic effect on the microscopic level can be understood via analysis of unfavorable ordering of water molecules around nonpolar solutes, where dynamic hydrogen bonds among water molecules nearby can be disrupted (1). The hydrophobic interaction is well known as one of the major driving forces for protein folding, and is also a key factor to stabilize the globular or binding structures of single protein, multiprotein, and protein−ligand systems (2-5). According to previous studies, the hydrophobicity of proteins can be attributed mainly to the side chains of amino acid residues, which are the structural units of protein backbones (5-7). Hence, quantitative characterization of the hydrophobicity of amino acids in protein environment is crucial to our understanding of the protein functionalities in biological environment and also to the prediction of synthetic peptide structures.Over the past three decades, extensive studies have been devoted to understanding hydrophobic interaction and hydrophobic hydration on the molecular levels (8-37). However, the quantitative description of the hydrophobicity of protein and amino acid residues still largely hinges on molecular thermodynamic properties of the residues rather the structural properties of the protein polymer itself. In engineering fields,...

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