Protein sequence and structure: Is one more fundamental than the other?

TL;DR

This paper proposes that protein native states form a unique phase of matter characterized by a sequence-independent free energy landscape, which explains folding efficiency and structural characteristics.

Contribution

It introduces a novel phase concept for protein native states, emphasizing the role of a common free energy landscape in protein folding and design.

Findings

Proteins exhibit a sequence-independent free energy landscape.

The novel phase facilitates rapid and cooperative folding.

Sequence design can efficiently start from random peptides.

Abstract

We argue that protein native state structures reside in a novel "phase" of matter which confers on proteins their many amazing characteristics. This phase arises from the common features of all globular proteins and is characterized by a sequence-independent free energy landscape with relatively few low energy minima with funnel-like character. The choice of a sequence that fits well into one of these predetermined structures facilitates rapid and cooperative folding. Our model calculations show that this novel phase facilitates the formation of an efficient route for sequence design starting from random peptides.