EcoO109I is a type II restriction endonuclease, which provides a defense mechanism by degrading foreign DNA and crystallography studies suggested a possibility of an existence of domain motion, which assists for capturing DNA. To prove the existence of domain motions in EcoO109I we combined MD simulation and small-angle X-ray scattering (MD-SAXS). It was found that SAXS profile in solution clearly showed the deviation from that in the crystal, implying that SAXS profile gives us the averaged structure in motion. We then performed MD simulation and calculated the time-averaged SAXS profile and SAXS profile from MD could describe the experimental one. Further MD simulation studies revealed a large fluctuation of radius of gyration with a period of ~ 50ns due to domain motion, which might be related to enzyme reaction. In order to observe the domain motion in this protein directly we propose to perform NSE study on EcoO109I and we will also verify whether or not such observed domain motion is really relevant to its mechanism of enzyme reaction by comparing to MD results.