is usually a tedious and expensive process whereby the target macromolecule must be produced in relatively large quantities and purified in high concentrations. A successful experiment often requires expert knowledge of biochemistry, bioinformatics and molecular biology. Over the past decades, rapid technical advances in DNA cloning, protein expression and purification methodologies have made it generally easy to obtain enough amount of proteins for their structural study. Besides, numerous innovations and improvements have been made in solving protein structures using instrumental methods such as X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy and electron microscopy (EM). These efforts together have given rise to dramatic accumulation of 3-D structural data in the past few decades (Figure 1). The large number of protein structures will certainly yield valuable information to the rules for elucidating protein folding/unfolding mechanisms and understanding their biological functions.