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It is of fundamental importance in pharmacology and theoretical biology to analyze the binding of ligands to receptors. A better understanding of this process and its outcomes can help predict the following: how the protein interacts with ligands; whether the ligand acts as an activator, inhibitor, or substrate; in which areas the ligand interacts best with the receptor. This article describes the potential of using a software pipeline for finding the most probable position of the ligand in the receptor. Such a pipeline involves a complex algorithm, from predicting the structure of the receptor to searching and analyzing the interaction of ligands with the receptor. The advantage of the software pipeline is that it allows numerous combinations of ligands and receptors to be analyzed at once. Possible interactions of the receptor–ligand complex are studied based on certain parameters: the energy of the affinity of the ligand for the receptor; the length and energy of the bond between the receptor and the ligand, both in the whole complex and between individual atoms. All characteristics can be automatically calculated by default under the specified optimal parameters. Alternatively, they can be set by the user, depending on the task. To illustrate how the software pipeline works, we analyzed the interaction of ligands with human acetylcholinesterase, a protein with the most studied active center. We confirmed that the software pipeline works correctly by comparing the obtained results with the experimental data on the binding of various ligands to human acetylcholinesterase. The pipeline code was published on GitHub (https://github.com/NastiaKozlova/stabilisation complex-receptor-ligand).

Conformational effects of interaction between bovine and human serum albumin (SA) molecules and nanoparticles of shungite carbon (ShC) in aqueous dispersion have been studied in the temperature range 17 – 72 °С K using electron spin resonance (EPR) spin probing (P). The temperature and kinetic dependences of the parameters of the EPR spectrum for solutions and dispersions of SA and ShC as well as for their mixtures have been obtained. The interaction of SA molecules with ShC nanoparticles has been shown to affect significantly the thermally induced protein conformational changes that determine the ability of the SH group of Cys-35 of SA to convert the NO group of the doxyl stearic fatty acid (FA) used as the probe to diamagnetic state. The temperature transitions reflecting the SA conformational changes in the localization region of P become less pronounced and shift toward higher temperatures in the presence of ShC. This may be due to a change in the oxidation-reduction balance of the set of SA molecules in solution or dispersion, since ShC acts as an oxidant with respect to SA. Therefore, ShC can also be considered an agent affecting the degree of oxidation of Cys-34 of SA with free radicals, such as P. ShC nanoparticles and P compete with each other during the oxidation of Cys-34. Furthermore, the transfer of P from SA to nanoparticles is facilitated due to the conformational transitions, and the reduction of the probe NO group by the protein SH groups is impeded. This allows considering ShC nanoparticles a factor of regulation of the redox balance in systems involving SA, including physiological media.

An analysis of standard thermodynamic functions of protein structure in solution allows revealing important features of protein solution phase behavior, particularly the presence of higher and lower critical solution temperatures on phase diagram (PD). Linking the phase and the corresponding conformational transitions of protein molecules to phase transitions of the protein solution as a whole will provide consideration of the relationship between protein conformation and the structural organization of protein systems in predenaturational interval. A phase diagram (PD) for the globular protein solution is presented in the temperature-entropy coordinate plane. Solution phase states have been analyzed and a probable interrelation of topological structures arising in the supercritical region with the phase processes in low- and high-temperature range has been defined when considering PD. This shows the possibility to superpose two types of PD: for normal and retrograde protein solubility. PD in the temperature-packing density plane has been presented for a protein solution with low and high critical solution temperatures and a supercritical zone between them typical of native protein solution, and a closed zone typical of denatured protein solution in the near physiological temperature interval. Supramolecular organization of protein solution has been described on this basis including metastable phases of protein molecules in conformations altered with respect to native (N) and denatured (D) states as well as dynamical protein clusters and oligomers in the supercritical zone. The contribution of the solvent in the low- and high-temperature ranges has also been taken into account. Various PD regions have been interpreted under the assumption that molecules in conformations, corresponding to N and D states are capable of forming different nanocrystal lattices which define the topological features of the corresponding solutions in a wide temperature range. Probable significance of supercritical phase states of protein solutions for the self-regulation of the components chemical potentials at the expense of the solution supramolecular organization at changing temperature and/or salt concentration and thereby at changing environmental factors has been discussed.