A topological perspective into the sequence and conformational space of proteins

TL;DR

This paper explores the topological relationship between amino acid sequences and protein structures, showing that residue arrangement alone can determine designability without energy calculations, using lattice models.

Contribution

It demonstrates the isomorphism between sequences and structures in lattice proteins and highlights the importance of topology over energetics in protein design.

Findings

Topological arrangement suffices to determine designability.

Exact enumeration shows feasibility of lattice models for long chains.

Connectivity of residues is fundamental to structure design.

Abstract

The precise sequence of aminoacids plays a central role in the tertiary structure of proteins and their functional properties. The Hydrophobic-Polar lattice models have provided valuable insights regarding the energy landscape. We demonstrate here the isomorphism between the protein sequences and designable structures for two and three dimensional lattice proteins of very long aminoacid chains using exact enumerations and intuitive considerations.We emphasize that the topological arrangement of the aminoacid residues alone is adequate to deduce the designable and non-designable sequences without explicit recourse to energetics and degeneracies. The results indicate the computational feasibility of realistic lattice models for proteins in two and three dimensions and imply that the fundamental principle underlying the designing of structures is the connectivity of the hydrophobic and polar residues.