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CYP1A2,one of the major members of cytochrome P450 in human liver,can metabolize phenacetin efficiently.A mutation distant from the active site,F186L could significantly lower its phenacetin o-deethylation activity.Here we used molecular dynamics(MD)simulations to wild type and F186L mutant of CYP1A2,as well as their complexes constructed from ensemble docking,so as to illustrate the possible reasons of the distant inhibition on the enzyme activity from the perspective of structure-function relationship.It was found that the F186L mutation changed the binding mode of phenacetin,decreased its stability in the active site,and greatly affected the open ratio of channels accessing the active site,mainly through collective conformational changes of multiple domains characterized by the formation of a single hydrogen bond between Tyr189 and Asp320,located in the core of enzyme.The mechanism of long-range effect between the F186L mutation site and the active site may provide a new typical example of the allosteric communication pathway within the enzyme.