An intrinsic property of protein critical to function is the ability of undergoing conformation change upon ligand binding or biochemical modification. In this work, we study Adenylate Kinase (AKE), an important enzyme controlling the balance of ATP in prokaryotic cells. X-ray crystallography indicates that AKE has two distinct conformations, open and closed, depending on whether it is bound with substrates (ATP and AMP). Conformation difference in AKE is determined by the relative position of two separate domains, the lid domain and the NMP binding domain, to the core. In this work, we use all-atom molecular dynamics (MD) simulations and coarse-grained modeling to understand the effects of ligand binding on AKE conformation. Results based on four ~100ns all-atom trajectories indicate that ATP binding induced the closing of lid domain and suggest that the relative population between closed to open structure is increased as a result. The closing of NMP binding domain, however, is found to be more specific and may require a timescale longer than 100ns to close. The mechanical property of a hinge region is found to correlate with lid closing; residues in this region may be mutated to alter the rate of conformational change and hence enzyme catalysis. This prediction agrees well with the results of recent single molecule experiments. Using a double-well network coarse-grained model, multiple pathways of open-to-closed transition can be found. Motions of lid-domain and NMP binding domain are not entirely concerted and may be treated as two distinct events. This picture is different from the result of using elastic network model and agrees better with atomistic simulations. In addition to open-to-closed transition, solvation structures and intrinsic mechanical properties of AKE are also characterized to identify key residues that may control the conformational change of AKE from mechanical perspectives.