International Scientific Journals
of Scientific Technical Union of Mechanical Engineering "Industry 4.0"

Metal ions are essential for the structural stability and catalytic activity of numerous metalloproteins involved in cellular regulation and signaling. Protein phosphatases such as PHLPP2 and PPM1A play a key role in phosphorylation-dependent pathways with direct biomedical relevance, including cancer-related signaling mechanisms. Still, the factors governing metal selectivity in their active sites remain insufficiently understood. In the present study, Density Functional Theory (DFT) calculations are employed to investigate the metal preferences of two structurally distinct phosphatases: PHLPP2, characterized by a mononuclear Zn²⁺ binding site, and PPM1A, containing a binuclear Mn²⁺ catalytic center. The calculations are performed at the B3LYP/6-31+G(3d,p) level of theory to assess the thermodynamics of metal substitution in biologically relevant coordination environments. The results indicate pronounced differences in structural protection and solvent accessibility between the two metal-binding sites, with the Zn²⁺ site in PHLPP2 exhibiting high thermodynamic stability and well-pronounced protection against competing divalent metal ions. In contrast, the binuclear Mn²⁺ center in PPM1A demonstrates greater flexibility and increased susceptibility to metal exchange, particularly in the presence of biologically abundant cations. Overall, the study demonstrates the applicability of DFT calculations as a predictive tool for investigating metal selectivity in metalloproteins and provides further insight into the possible prospects of innovative cancer-treatment strategies in biologically relevant systems.

Recently, supramolecular complexes based on synthetic macrocyclic host molecules have received much attention due to their broad applications as drug delivery carriers, biological and chemical sensors, light-emitting materials, bioimaging agents, etc. Cucurbit[n]urils are cavitands known for their high affinity for various guest molecules, although some aspects of their coordination chemistry remain enigmatic. They are still not tested as metalloenzyme models and not much is known about their metal-binding properties. Furthermore, there is no systematic study on the key factors controlling the processes of metal coordination to these systems. In the
computational study herein, DFT molecular modeling has been employed in order to investigate the interactions of biologically essential mono- (Na+), di- (Mg2+) and some trivalent (La3+, Lu3+) metal cations to cucurbit[n]urils and evaluate the major determinants shaping the process of recognition. The thermodynamic descriptors (Gibbs energies in the gas phase and in a water medium) of the corresponding complexation reactions have been estimated. The results obtained shed light on the mechanism of host–guest recognition and disclose which factors more specifically affect the metal binding process.

One of the main problems in modern society is related to improper and insufficient nutrition, as a result of which various diseases develop, the treatment of which requires additional intake of vitamins in the form of nutritional supplements. Fat-soluble vitamins have important biological activities, but their application is limited due to their low solubility and stability. One way to improve their properties is to incorporate them into complexes with host molecules, such as cyclodextrins, the most commonly used host molecules in the pharmaceutical industry. The theoretical study presented here aims at delianating the interactions of vitamin K3 and its analog phthiocol with β-CD drug delivery system. To achieve this goal, 1:1 complexes of different forms of vitamin K with β-CD were modeled. The influence of various factors on the thermodynamics of interactions of the guest molecules with the macrocycle (host molecule) was evaluated.