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The amino acid sequence of a polypeptide chain is what determines the chain's ability to fold to a functional unique structure, or stay disordered but functional, or misfold to a potentially pathogenic conformation. Even at the level of its amino acid composition the sequence can determine certain global properties of a protein, such as its ability to form a globular structure or remain extendedly disordered and define the predisposition of ordered proteins to either possess or lack equilibrium partially folded intermediates. Finally, the sequence also defines the aggregation and misfolding susceptibility for proteins. Overall, amino acid sequences are hence responsible for protein folding, misfolding, and non-folding, and are used in computational tools as the sole input to predict these behaviors. The following review considers several of the aspects of the amino acid codes.

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