Topological origin of the protein folding transition

In this paper, a geometrical and thermodynamical analysis of the global properties of the potential energy landscape of a minimalistic model of a polypeptide is presented. The global geometry of the potential energy landscape is supposed to contain relevant information about the properties of a given sequence of amino acids, that is, to discriminate between a random heteropolymer and a protein. By considering the SH3 and PYP protein-sequences and their randomized versions it turns out that, in addition to the standard signatures of the folding transition-discriminating between protein sequences of amino acids and random heteropolymer sequences-also peculiar geometric signatures of the equipotential hypersurfaces in configuration space can discriminate between proteins and random heteropolymers. Interestingly, these geometric signatures are the shadows of deeper topological changes that take place in correspondence with the protein folding transition. The protein folding transition takes place in systems with a small number of degrees of freedom (very far from the Avogadro number) and in the absence of a symmetry-breaking phenomenon. Nevertheless, seen from the deepest level of topology changes of equipotential submanifolds of phase space, the protein folding transition fully qualifies as a phase transition.

Automated summary

This paper presents a geometrical and thermodynamical analysis of the potential energy landscape of a minimalistic model of a polypeptide. The study reveals that the global geometry and geometric signatures of the equipotential hypersurfaces can discriminate between proteins and random heteropolymers, providing valuable information in understanding the properties of amino acid sequences.