Application of Divergence Entropy to Characterize the Structure of the Hydrophobic Core in DNA Interacting Proteins

Barbara Kalinowska,Irena Roterman,Mateusz Banach,Leszek Konieczny

doi:10.3390/e17031477

Abstract

The fuzzy oil drop model, a tool which can be used to study the structure of the hydrophobic core in proteins, has been applied in the analysis of proteins belonging to the jumonji group—JARID2, JARID1A, JARID1B and JARID1D—proteins that share the property of being able to interact with DNA. Their ARID and PHD domains, when analyzed in the context of the fuzzy oil drop model, are found to exhibit structural variability regarding the status of their secondary folds, including the β-hairpin which determines their biological function. Additionally, the structure of disordered fragments which are present in jumonji proteins (as confirmed by the DisProt database) is explained on the grounds of the hydrophobic core model, suggesting that such fragments contribute to tertiary structural stabilization. This conclusion is supported by divergence entropy measurements, expressing the degree of ordering in each protein’s hydrophobic core.

Highlights

Hydrophobic interactions are traditionally regarded as responsible for tertiary structural stabilization [1,2,3,4,5,6,7,8,9,10]
The fuzzy oil drop model can be used with any hydrophobicity scale
The Supplementary Tables (Tables S1–S9) show this observation with respect to the status of the selected fragments of polypeptides. The comparison of these values suggests consistency of the results based on different hydrophobicity scales applied to fuzzy oil drop model

Summary

Introduction

Hydrophobic interactions are traditionally regarded as responsible for tertiary structural stabilization [1,2,3,4,5,6,7,8,9,10]. We assume that the idealized hydrophobic core structure, by virtue of its ordered form, enhances the protein’s structural stability At this point we should emphasize that, by referring to a “hydrophobic core”, we mean the entire distribution of hydrophobic density throughout the protein body, including its outer hydrophilic layers, which render the protein watersoluble. We have extended Kauzmann’s original “oil drop” abstraction with a mathematical formalism which models the idealized “droplike” protein structure using a 3D Gaussian function [12] This function peaks at the central point of its independent variable range, with values decreasing with distance from the center (bell curve) and approaching 0 at a distance of 3σ in each direction (the so-called three-sigma rule). The parameters x , y , z are the peak of the Gaussian function and σ x , σ y , σ z represent the Gaussian function on each of the three principal directions: according to the three-sigma rule, over 99% of the function’s integral is contained in an area given by ( x ± 3σ ) .When considering three dimensions, the corresponding assumption is that 99% of the protein’s hydrophobic density is contained in an ellipsoid bounded by ( x ± 3σ x , x ± 3σ y , x ± 3σ z ) and that the Gaussian can be safely truncated beyond these limits

Objectives

Methods

Results

Conclusion