Dynamics of non-covalent interactions during the P–O bond cleavage reaction by ribonuclease A†

Abstract

In this work, an atomistic-scale investigation of the phosphodiester P–O bond cleavage reaction by the enzyme ribonuclease A was carried out using computer simulation techniques. It is shown that during the reaction the network of non-covalent interactions in the active center of the ribonuclease changes significantly, while the role of these non-covalent interactions is different: coordination of the corresponding groups, electron density transfer, and ligand holding in the active center. It is shown that the process of proton transfer from Asp121 to His119 is the first stage of this reaction; at the same time, the hydrogen bond between the phosphate ligand and the imino group of Arg39 is broken, which, although keeping the ligand in the active center, does not allow the ligand to orient itself more conveniently for subsequent proton transfers. Furthermore, the key step of this reaction occurs: proton transfer with the participation of imidazole rings His12 and His119, in which the guiding role is played by several hydrogen bonds with the participation of Phe120, and the role of an electron density carrier is played by the pnictogen bond between the oxygen of the phosphate ligand and the pyridine-like nitrogen of the imidazole ring His119, which was detected for the first time.