Abstract:

Using the docking module FlexX in the SYBYL molecular modeling suite，a total of 66 enantiomers were docked to four lipases to predict the enantioselectivity of these lipases. In this process，the substrate analogs of tetrahedral intermediates were covalently docked to the active sites of lipases. Docking conformations without all the three essential H-bonds were discarded. The docking result indicated that the binding energy difference between the two enantiomers was not significant enough to accurately predict the enantiopreference of the enzymes when enantioselectivity was lower than 100. And the prediction ratio increased to 81.5% obviously，when enantioselectivity was higher than 100 and the substrate contained fewer backbone carbons. During the docking process，productive conformations were formed between most substrates and lipases，which were in accordance with the theoretical catalytic mode. Besides，owning to its high computing rate，this method can be applied to modeling and prediction of potential substrates of lipases with high throughput.