Abstract:

The molecular dynamics simulation method was used to study the catalytic activity of VmoLac non-specific substrates. Four systems of VmoLac/3-oxo-C10-AHL， VmoLac/3-oxo-C6-AHL， VmoLac/γ-nonalacton and VmoLac/ethyl-paraoxon complexs were simulated. The main reasons for the conformational changes caused by the binding of different substrates to VmoLac were analyzed. The analysis results show that the 3-oxo-C10-AHL and γ-nonalacton combination can make the active pocket near Loop8 structure domain motion obviously. The flexible conformation made it easier for the substrate to bind to the outside of the hydrophobic channel of Loop8， which was conducive to the catalytic reaction. VmoLac activity around the pocket gating residues W264 and Y230 changes will affect the distance between the combination of the substrate. The distance between Y98 and the carbonyl carbon of long-chain lactone and nonolactone was relatively small， while the distance between Y98 and the carbonyl carbon of short-chain lactone and the phosphorus atom of phosphorus oxide was relatively large. Shorter distance was more conducive to the occurrence of nucleophilic offensive reaction. D257 was the key residue that initiated the VmoLac catalytic reaction. When VmoLac catalyzed 3-oxo-C10-AHL or γ-nonalacton， D257 formed more hydrogen ^{bonds with polarized water and substrate， which made the substrate more easily bind to the enzyme. VmoLac had a stronger ability to catalyze long-chain lactones than short-chain lactones， and a stronger ability to catalyze long-chain lactones than phosphorus oxides from the perspective of theoretical catalytic mechanism， which provides theoretical proof for the experimental structure.}

Key words: Phosphotriesterase-like lactonases（PLLs）, VmoLac, Autodock, Molecular dynamics simulation