The organophosphorous hydrolase (PTE) from Brevundimonas diminuta is capable of degrading extremely toxic organophosphorous compounds with a high catalytic turnover and broad substrate specificity.Although the natural substrate for PTE is unknown, its loop remodeling (loop 7-2/H254R) led to the emergence of a homoserine lactonase (HSL) activity that is undetectable in PTE (Kcat/km values of up to 2 × 104), with only a minor decrease in PTE paraoxonase activity.In this study, homology modeling and molecular dynamics simulations have been undertaken seeking to explain the reason for the substrate specificity for the wild-type and the loop 7-2/H254R variant.The cavity volume estimated results showed that the active pocket of the variant was almost two fold larger than that of the wild-type (WT) enzyme.pKa calculations for the enzyme (the WT and the variant) showed a significant pKa shift from WT standard values (ApKa =3.5 units) for the His254residue (in the Arg254 variant).Molecular dynamics simulations indicated that the displacement of loops 6 and 7 over the active site in loop 7-2/H254R variant is useful for N-acyl-L-homoserine lactone (C4-HSL) with a large aliphatic chain to site in the channels easily.Thence the expanding of the active pocket is beneficial to C4-HSL binding and has a little effect on paraoxon binding.Our results provide a new theoretical contribution of loop remodeling to the rapid divergence of new enzyme functions.