ИСТИНА

The processes that determine the nature of life are stages of an endless chain of intermolec-ular interactions involving biomacromolecules. The study of the molecular basics of the in-teraction of biomacromolecules with each other, with low molecular weight ligands, with metal ions, etc. lies at the heart of biochemistry, molecular biology and other life science disciplines. NMR spectroscopy is one of the most important tools for studying protein-ligand interactions. NMR provides a wide variety of techniques for determining the struc-ture of protein-ligand complexes, detecting ligand binding sites, determining the stoichiom-etry of the protein-ligand interaction, measuring ligand binding constants. NMR screening techniques have been developed for design of compounds build from small molecular frag-ments and capable to bind specifically to the desired center of the target protein. Several examples of the use of modern NMR spectroscopy tools for the studies of protein-ligand interactions are presented. Thus, structure and dynamics of several complexes of the pharmacologically important enzyme dihydrofolate reductase with the antibacterial drug trimethoprim have been investigated in order to reveal the nature of the cooperative effects of ligand binding. Interaction interface of the human translation termination factor eRF1 with the eukaryotic ribosome has been determined using the heteronuclear NMR methods. NMR screening techniques have been successfully applied for the design of inhibitors of the methionine γ-lyase, compounds with potential antibacterial properties. NMR methods have been used to study interactions of the fragments of β-amyloid peptide isoforms with zinc ions in order to understand the molecular mechanism of the initial stages of β-amyloid aggregation linked to the Alzheimer's disease. More recently, NMR techniques have been applied to study interaction of the N-terminal domain of the main reverse transcriptase subunit of yeast telomerase with its potential part-ners in the catalytic cycle of the process of chromosome elongation catalyzed by telomerase. The above examples illustrate the high capabilities of NMR spectroscopy in the studies of protein-ligand interactions.