Background: Understanding the folding mechanism of the β-sheet structure is crucial for a general and comprehensive understanding of the protein folding problems.The WW domain families are named by the two conserved tryptophan residues, and are the smallest natural β-sheet structures.An artificial protein CC45 is designed by the coupled conservation model and is capable of folding into the same structure as WW domain.These WW domain proteins are usually regarded as one of the simplest models for understanding the folding mechanism of β-sheet.