Why are ?natively unfolded? proteins unstructured under physiologic conditions?

TLDR

Natively unfolded proteins lack ordered structure under neutral pH in vitro, occupying a unique niche in the protein kingdom. The authors analyzed amino acid sequences using normalized net charge and mean hydrophobicity to compare small globular folded proteins with natively unfolded ones. They found that natively unfolded proteins cluster in a distinct region of charge‑hydrophobicity phase space, characterized by low hydrophobicity and high net charge. © 2000 Wiley‑Liss, Inc., Proteins 41:415–427.

Abstract

"Natively unfolded" proteins occupy a unique niche within the protein kingdom in that they lack ordered structure under conditions of neutral pH in vitro. Analysis of amino acid sequences, based on the normalized net charge and mean hydrophobicity, has been applied to two sets of proteins: small globular folded proteins and "natively unfolded" ones. The results show that "natively unfolded" proteins are specifically localized within a unique region of charge-hydrophobicity phase space and indicate that a combination of low overall hydrophobicity and large net charge represent a unique structural feature of "natively unfolded" proteins. Proteins 2000;41:415–427. © 2000 Wiley-Liss, Inc.