Proteins are heteropolymers of α-amino-acid building blocks critical to the functional logic of living state.1 As heteropolymers they are unique in their ability to adopt under physiological condition three-dimensional folds specific in conformation. These so-called native folds have α-amino-acid structures as their coding alphabet. The protein folding under the α-amino-acid codes, effectively polypeptide folding under the side-chain codes is crucial for the biological functions of enzymes, antibodies, etc. Indeed, the diversity of protein roles dependent on their ordering to specific conformation includes the catalytic functions recognition of enzymes and the functions of antibodies.2 The ordering of proteins as functionally specific folds with the codes of side-chain alphabet is regarded as the second genetic code given its importance to the expression of genomes. The understanding of the code remains one of the major unsolved puzzles of the modern science. The puzzle of sequential control of conformation has its energetic bases hidden in the size and complexity of proteins and their relevant physiological and thermodynamic systems. characterizations