Protein structures and optimal folding emerging from a geometrical variational principle

TL;DR

This paper introduces novel numerical techniques to analyze protein folding, revealing the dominant role of backbone geometry and suggesting an extremality principle underlying protein evolution and structure formation.

Contribution

It demonstrates that protein native states have many conformations with similar structural overlap, highlighting the importance of geometry in folding and evolution.

Findings

Native states have many conformations with similar structural overlap.

Conformational entropies are nearly equal among unrelated proteins of the same length.

Results suggest an extremality principle in protein evolution.

Abstract

Novel numerical techniques, validated by an analysis of barnase and chymotrypsin inhibitor, are used to elucidate the paramount role played by the geometry of the protein backbone in steering the folding to the correct native state. It is found that, irrespective of the sequence, the native state of a protein has exceedingly large number of conformations with a given amount of structural overlap compared to other compact artificial backbones; moreover the conformational entropies of unrelated proteins of the same length are nearly equal at any given stage of folding. These results are suggestive of an extremality principle underlying protein evolution, which, in turn, is shown to be associated with the emergence of secondary structures.