Structural disorder originates beyond narrow stoichiometric margins of amino acids in naturally occurring folded proteins.

Rigorous analyses of Euclidean distances between non-peptide bonded residues in structures of several thousand naturally occurring folded proteins yielded a surprising "margin of life" for percentage occurrence of individual amino acids in naturally occurring folded proteins. On one hand, the concept of "margin of life", referring to lower than expected variances in average stoichiometric occurrences of individual amino acids in folded proteins, remains unchallenged since its discovery a decade ago. On the other hand, within this past decade there has been a strong emergence of a gradual paradigm shift in biology, from sequence-structure-function in proteins to sequence-disorder-function, fuelled by discoveries on functional implications of intrinsically disordered proteins (primary sequences that do not form stable structures).