Properties and Activity of Peptide Derivatives of ACE2 Cellular Receptor and Their Interaction with SARS-CoV-2 S Protein Receptor-Binding Domain.

The aim of this work was to design and characterize peptides based on the α-helices h1 and h2 of the ACE2 receptor, forming the interaction interface between the receptor-binding domain (RBD) of the SARS-CoV-2 S protein and the cellular ACE2 receptor. Monomeric and heterodimeric peptides connected by disulfide bonds at different positions were synthesized. Solubility, RBD-binding affinity, and peptide helicity were experimentally measured, and molecular dynamics simulation was performed in various solvents. It was established that the preservation of the helical conformation is a necessary condition for the binding of peptides to RBD. The peptides have a low degree of helicity and low affinity for RBD in water. Dimeric peptides have a higher degree of helicity than monomeric ones, probably due to the mutual influence of helices. The degree of helicity of the peptides in trifluoroethanol is the highest; however, for in vitro studies, the most suitable solvent is a water-ethanol mixture.

[Analysis of dihydroquercetin physical modification via in vitro and in silico methods]. / Analiz fizicheskikh modifikatsii digidrokvertsetina in vitro i in silico.

Flavonoid-mediated materials are promising substances for the design of new functional materials because of their bioactivity, eco-friendliness, and cost-effectiveness. Dihydroquercetin (DHQ) is the major flavonoid in the wood of Larix dahurica Turcz. Previously some new modifications were created on the basis of DHQ, they were characterized by different morphological, physico-chemical and biopharmaceutical properties. This study was performed to research the influence of the solvent on the formation of the solid phase in DHQ microtubes and crystal form as commercially available active pharmaceutical ingredient (API). The choice of the models for the computational simulation was based on the data of differential scanning calorimetry. All calculations were performed using Materials Science Suite. In silico analysis demonstrated that the molecules of solvent are a key player in the formation of the solid phase of the flavonoid-mediated material. Also the comparative analysis of physical characteristics between DHQ microtubes and crystal form was performed. These data give an opportunity to suggest, that DHQ microtubes may have a grate application as the dressing material and in the drug delivering. The results of this study could be helpful for the design of the new flavonoid-mediated materials by crystal engineering.

Structural Insight Into the Role of Mutual Polymorphism and Conservatism in the Contact Zone of the NFR5-K1 Heterodimer With the Nod Factor.

Sandwich-like docking configurations of the heterodimeric complex of NFR5 and K1 Vicia sativa receptor-like kinases together with the putative ligand, Nod factor (NF) of Rhizobium leguminosarum bv. viciae, were modeled and two of the most probable configurations were assessed through the analysis of the mutual polymorphisms and conservatism. We carried out this analysis based on the hypothesis that in a contact zone of two docked components (proteins or ligands) the population polymorphism or conservatism is mutual, i.e., the variation in one component has a reflected variation in the other component. The population material of 30 wild-growing V. sativa (leaf pieces) was collected from a large field (uncultivated for the past 25-years) and pooled; form this pool, 100 randomly selected cloned fragments of NFR5 gene and 100 of K1 gene were sequenced by the Sanger method. Congruence between population trees of NFR5 and K1 haplotypes allowed us to select two respective haplotypes, build their 3D structures, and perform protein-protein docking. In a separate simulation, the protein-ligand docking between NFR5 and NF was carried out. We merged the results of the two docking experiments and extracted NFR5-NF-K1 complexes, in which NF was located within the cavity between two receptors. Molecular dynamics simulations indicated two out of six complexes as stable. Regions of mutual polymorphism in the contact zone of one complex overlapped with known NF structural variations produced by R. leguminosarum bv. viciae. A total of 74% of the contact zone of another complex contained mutually polymorphic and conservative areas. Common traits of the obtained two stable structures allowed us to hypothesize the functional role of three-domain structure of plant LysM-RLKs in their heteromers.

[Prediction of Protein Conformational Mobility and Evaluation of Its Reliability Using Small-Angle X-ray Scattering].

The "coarse-grained" model of protein conformational mobility is presented. We compared the trajectories of conformational motions predicted for five proteins using this model with the motion obtained by the method of the "nearest neighbor", based on small-angle X-ray scattering data. It is shown that for all studied proteins the sequence of conformations calculated on the basis of "coarse-grained" model and on the basis of the "nearest neighbor", coincides well, although there are exceptions. Some separate consideration should be given to each protein to discern the causes of these exceptions.