INTERACTION OF HYDROPHOBIC
MOLECULES IN AN AQUEOUS
Specific properties of water determine the behavior of dissolved molecules. The presence of a hydrogen bond network plays an important role in this case. It should be noted that water forms a very mobile net-work in the liquid state, in which hydrogen bonds always switch from one molecule to another.
Tendency of water molecules to form optimal network results in hydrophobic interaction phenomenon, which is interpreted as the force pulling molecules to each other.
The nature of this force is different from Coulomb or van der Waals forces. This interaction is not direct and acts through the structural rearrangement of surrounding water and hydrogen bond network. Water tends to form an optimal hydrogen bond network, which considers the presence of hydrophobic molecules, which results in their approach and thus cluster and clathrate structure formation.
Let us consider this process in detail.
We assume that positive values of potential energy of paired electrostatic interaction between hydrophobic amino acid residues indicate a repelling nature at small distances (in our case). However, when they are located in aqueous environment, which is characterized by the highdegree of ordered interaction between water molecules, hydrophobic clusters are formed. It should be noted that water molecules tend to
have a strong interaction between each other due to nonuniform distribution of electron density between an oxygen atom and two hydrogen atoms.
The character of formation of water molecules is that the electron density around an oxygen atom is much higher than that near hydrogen atoms, which in turn results in dipole formation, the ends of which carry unlike charge signs. The presence of such a dipole in a water molecule results in strong interaction with another dipole of water molecules; the environment of an oxygen atom carries a negative charge, while a hydrogen atom environment carries a positive charge. As a result, the oxygen atom of one molecule attracts the hydrogen atom of another water molecule forming a highly ordered structure of water molecule dipoles. We assume that hydrophobic molecules, which are not characterized by strong dipole–dipole interactions and are intrinsic for dispersion interactions, would distort the ordered structure of water dipoles.
It should be noted that dispersion interactions arise between atoms due to fluctuations of electron density around the nucleus, which results in the appearance of an instant dipole moment at atoms and interaction of corresponding dipoles.
Dispersion interaction takes place between any atom groups; however, it is higher, when the polarizability of atoms is higher. In addition, dispersion forces play an important role in proteins during interaction of amino acid residues possessing hydrophobic (nonpolar) side radicals, such as valine, leucine, tryptophan, phenylalanine, and tyrosine.
The energy of dispersion interactions is inversely proportional to the sixth power of the distance between interacting atoms.
This implies that dispersion forces play a significant role only at short distances.
Water molecules tend to have strong interactions and “pull” hydrophobic molecules to occupy the minimum volume in a water environment along the entire contact volume so that they would not prevent the formation of ordered structure of water dipoles. Thus, compression force (squeezing) acts on hydrophobic molecules in a water environment during ordering, which provides the formation of conglomerates from hydrophobic molecules; on the contrary, their structures (between hydrophobic molecules) are influenced by electrostatic interaction (with a positive sign magnitude), which results in repulsion of hydrophobic molecules from each other at small distances (Fig. 2). Because repulsion forces between atoms, which are related to repulsion of electron clouds during their interdigitation, manifest themselves.
This statement is rationalized by the fact that a molecule possesses both positive and negative charges, which are distributed nonhomogeneously by the molecule, as a result of which one side of the molecule is positively charged, while the other side is negatively charged. In addition, a significant fraction of the negative charge is distributed along the “external” electron shell, while the positive charge is located in nuclei of the atoms in molecules. Firstly, this results in the fact that molecules face each other with oppositely charged sides (plus to minus). Then, due to the fact that the electric field is nonuniform around the charge and possesses a gradient, that is, decays over a distance (proportionally to the square distance), it appears at relatively large distances that the attraction force between oppositely charged parts facing each other is marginally higher than the repulsion force between like-charged sides (though charges are identical, the distances are different due to turn of orientation, as well as forces are different); however, when molecules approach each other and their electron shells are very close to each other (in our case), it appears that the repulsion force between likely charged electron shells exceeds the attraction between the nuclei of one molecule and electron shells of another and the molecules would repel at such distance.
In this case, the attraction forces from the dipoles of water molecules are significantly higher than repulsion forces between hydrophobic molecules
ANALYSIS OF THE INTERACTION
OF TWO PROTEINS ILLUSTRATED
BY THE FORMATION OF A NAP1–NAP1
A new method is presented that allows you to analyze the potential energy of electrostatic interactions of protein complexes with point substitutions of amino acid residues taking into account three-dimensionalncomplex structure by the example of the formation of the Nap1 – Nap1 dimer Potential maps were developed energy of electrostatic interaction of paired amino acid residues involved proteins. The analysis of interacting proteins taking into account the three-dimensional structure.
The constructed model allows to melt such changes in affinity and choice of amino acids lots, the composition of the polypeptide chains to increase affinity of the biological complex and increase binding selectivity. In addition, to each mutant pathogenic protein, we can choose a specific inhibitor, taking into attention changes in conformation and redistribution electrostatic potential.
Amino acid residues of two polypeptide chains of two Nap1 proteins, which were replaced by hydrophobic tryptophan, are underlined. With the replacement of amino acid residues (six charged amino acids and one hydrophilic amino acid) by hydrophobic amino acid residues, a significant predominance of potential energy of paired electrostatic interaction is observed in the positive range of “high” values (21st exponent). Such behavior of hydrophobic amino acid residues in a water environment can be interpreted as “forced attraction.” In this case, we suggest that the water environment “forces” hydrophobic amino acid resi-dues to approach each other
Analysis of the interaction of two proteins on the example of education
homodimer Nap1 − Nap1
FORMATION OF A HYDROPHOBIC CLUSTER DUE TO SEVERAL REPLACEMENTS OF AMINO ACIDS IN PROTEINS: E110W, K111W, E112W, AND E116W OF ONE NAP1 PROTEIN AND E121W, N122W, AND Q126W OF ANOTHER NAP1 PROTEIN
Figure 5a shows the graphical representation of the matrix of potential energy of interaction from 82 to 120 amino acids of wild-type Nap1–Nap1 protein. Figure 5b shows the formation of a Nap1–Nap1 protein upon replacement of E110, K111, E112, and E116 amino acid residues of the one Nap1 protein and E121, N122, and Q126 of another Nap1 protein by hydrophobic tryptophan (W).
The formation of a hydrophobic cluster due to several replacements of amino acids in proteins:
Electrostatic interaction energy, J
Replacement of hydrophilic a.a. T101A per hydrophobic amino acid residue
During the interaction of wild-type Nap1–Nap1 proteins, T101 (threonine 101) is characterized by a sufficiently high negative value of potential energy with K152 as compared to interactions of other amino acids; thus, hydrophilic threonine was replaced by hydrophobic alanine (A) and the potential energy of electrostatic interaction for such a replacement was recalculated. Let us present the part of the matrix in the range of key amino acid residues of two interacting proteins before and after replacement of T101A. As follows from Table 2, with the replacement of
T101A, there was an increase in the magnitude of potential energy of interaction. The values of potential energy in the positive range of values corresponding to the interaction of hydrophobic amino acids also appeared, which is considered as “attraction” in aqueous medium.
Figure 6 shows the region of two polypeptide chains of Nap1 and Nap1 proteins with indication of key amino acids, as well as indication of the change of potential energy of electrostatic interaction before and after replacement of T101A.
Electrostatic interaction energy,J
It should be noted that it became possible to quantitatively evaluate the hydrophobic effect on the basis of the developed model through computer simulation and calculate the potential energy of paired electrostatic interaction between each pair of hydrophobic amino acid residues of two polypeptide chains of proteins assuming conformation.
In this case, a dimer is formed by binding of two proteins in the opposite direction. The graph indicates the ordinal measurements of amino acid residues, while the countdown is from the 82nd amino acid residue of one protein Nap1 and the 83rd amino acid residue of Nap2, according to the database PDB: 5G2E