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.

Four de novo proteins differing in single mutation positions, with a chain length of 56 amino acids, represent diverse 3D structures: monomeric 3α and 4β + α folds. The reason for this diversity is seen in the different structure of the hydrophobic core as a result of synergy leading to the generation of a system in which the polypeptide chain as a whole participates. On the basis of the fuzzy oil drop model, where the structure of the hydrophobic core is expressed by means of the hydrophobic distribution function in the form of a 3D Gaussian distribution, it has been shown that the composition of the hydrophobic core in these two structural forms is different. In addition, the use of a model to determine the structure of the early intermediate in the folding process allows to indicate differences in the polypeptide chain geometry, which, combined with the construction of a common hydrophobic nucleus as an effect of specific synergy, may indicate the reason for the diversity of the folding process of the polypeptide chain. The results indicate the need to take into account the presence of an external force field originating from the water environment and that its active impact on the formation of a hydrophobic core whose participation in the stabilization of the tertiary structure is fundamental.

The presented analysis concerns the inter-domain and inter-protein interface in protein complexes. We propose extending the traditional understanding of the protein domain as a function of local compactness with an additional criterion which refers to the presence of a well-defined hydrophobic core. Interface areas in selected homodimers vary with respect to their contribution to share as well as individual (domain-specific) hydrophobic cores. The basic definition of a protein domain, i.e., a structural unit characterized by tighter packing than its immediate environment, is extended in order to acknowledge the role of a structured hydrophobic core, which includes the interface area. The hydrophobic properties of interfaces vary depending on the status of interacting domains—In this context we can distinguish: (1) Shared hydrophobic cores (spanning the whole dimer); (2) Individual hydrophobic cores present in each monomer irrespective of whether the dimer contains a shared core. Analysis of interfaces in dystrophin and utrophin indicates the presence of an additional quasi-domain with a prominent hydrophobic core, consisting of fragments contributed by both monomers. In addition, we have also attempted to determine the relationship between the type of interface (as categorized above) and the biological function of each complex. This analysis is entirely based on the fuzzy oil drop model.

One of the factors responsible for tertiary structural stabilization in proteins is the presence of the hydrophobic core—a result of hydrophobic interactions within the protein body. In some proteins (especially extracellular ones) additional stabilization is provided by covalent bonds between selected Cys residues, commonly referred to as disulfide bonds. The mutual interplay of both factors and their respective contributions to stabilization are the focus of this work. The assessment of the effects of disulfide bonds isinterpreted by Fuzzy Oil Drop (FOD) model in which individual polypeptide chain fragments (including fragments which participate in SS bonds) can be evaluated in the context of their influence upon tertiary structural stabilization by comparing their corresponding theoretical and idealized hydrophobicity density distributions. The proteins were identified with both factors reinforcing each other, as well as proteins where they seem to counteract each other. The analysis presents a number of enzymes, including ribonuclease, lysozyme, disulfide isomerase and phospholipase.

Protein solubility is based on the compatibility of the specific protein surface with the polar aquatic environment. The exposure of polar residues to the protein surface promotes the protein’s solubility in the polar environment. The aquatic environment also influences the folding process by favoring the centralization of hydrophobic residues with the simultaneous exposure to polar residues. The degree of compatibility of the residue distribution, with the model of the concentration of hydrophobic residues in the center of the molecule, with the simultaneous exposure of polar residues is determined by the sequence of amino acids in the chain. The fuzzy oil drop model enables the quantification of the degree of compatibility of the hydrophobicity distribution observed in the protein to a form fully consistent with the Gaussian 3D function, which expresses an idealized distribution that meets the preferences of the polar water environment. The varied degrees of compatibility of the distribution observed with the idealized one allow the prediction of preferences to interactions with molecules of different polarity, including water molecules in particular. This paper analyzes a set of proteins with different levels of hydrophobicity distribution in the context of the solubility of a given protein and the possibility of complex formation.

Research on the protein folding problem differentiates the protein folding process with respect to the duration of this process. The current structure encoded in sequence dogma seems to be clearly justified, especially in the case of proteins referred to as fast-folding, ultra-fast-folding or downhill. In the present work, an attempt to determine the characteristics of this group of proteins using fuzzy oil drop model is undertaken. According to the fuzzy oil drop model, a protein is a specific micelle composed of bi-polar molecules such as amino acids. Protein folding is regarded as a spherical micelle formation process. The presence of covalent peptide bonds between amino acids eliminates the possibility of free mutual arrangement of neighbors. An example would be the construction of co-micelles composed of more than one type of bipolar molecules. In the case of fast folding proteins, the amino acid sequence represents the optimal bipolarity system to generate a spherical micelle. In order to achieve the native form, it is enough to have an external force field provided by the water environment which directs the folding process towards the generation of a centric hydrophobic core. The influence of the external field can be expressed using the 3D Gaussian function which is a mathematical model of the folding process orientation towards the concentration of hydrophobic residues in the center with polar residues exposed on the surface. The set of proteins under study reveals a hydrophobicity distribution compatible with a 3D Gaussian distribution, taken as representing an idealized micelle-like distribution. The structure of the present hydrophobic core is also discussed in relation to the distribution of hydrophobic residues in a partially unfolded form.