WW domain proteins are usually regarded as simple models for understanding the folding mechanisrn of β-sheet.CC45 is an artificial protein that is capable of folding into the same structure as WW domain.In this article, the replica exchange molecular dynamics simulations are performed to investigate the folding mechanism of CC45.The analysis of thermal stability shows that β-hairpin 1 is more stable than β-hairpin 2 during the unfolding process.Free energy analysis shows that the unfolding of this protein substantially proceeds through solvating the smaller β-hairpin 2, followed by the unfolding of β-hairpin 1.We further propose the unfolding process of CC45 and the folding mechanism of two β-hairpins.These results are similar to the previous folding studies of formin binding protein 28 (FBP28).Compared with FBP28, it is found that CC45 has more aromatic residues in N-terminal loop, and these residues contact with C-terminal loop to form the outer hydrophobic core, which increases the stability of CC45.Knowledge about the stability and folding behaviour of CC45 may help in understanding the folding mechanisms of the β-sheet and in designing new WW domains.