The glycoside hydrolase family 1 β-D-glucosidase from rice(BGlu1)exists widely in rice organs with high level of activities [1].Rice BGlu1 is more efficiently to hydrolyze the β-(1,4)-linked glucooligosaccharides.It has a pair of catalytic glutamate residues serving as the acid/base and nucleophile in the active site,respectively[2].Mutations of β-glucosidase at catalytic glutamate residue make the hydrolytic activity decrease to a very low level.Nonnucleophilic mutations of rice BGlu1 nucleophile E386(Glycine,alanine,and serine)have been generated and the E386S mutant,acting as glycosynthase,catalyzed the most rapid accumulation of transglycosylation products.Hommalai G.et al proposed a rescue mechanism(Figure 1)catalyzed by a exogenous nucleophile of rice BGlu1[3].The quantum mechanical/molecular mechanical(QM/MM)method was used to investigate this rescue mechanism.E386S mutant experiences a concerted process to glycosylate the anionic formate with an energy barrier of 21.7 kcal/mol.The low energy barrier of the mutated complex shows that anionic formate can function as a good nucleophile to attack the anomeric carbon atom.Our calculations tell people how to select exogenous nucleophiles in the future study of β-glucosidase.