# Proteins: the physics of amorphous evolving matter

## TL;DR

This paper explores a unified physical and evolutionary framework for understanding proteins, modeling them as evolvable condensed matter and analyzing how genetic mutations influence protein structure and function.

## Contribution

It introduces a mechanical model treating proteins as evolvable matter and uses Green's functions to connect genetic mutations with physical interactions.

## Key findings

- Mutations cause localized perturbations in proteins.
- Green's functions link genetic epistasis to amino acid interactions.
- The framework aids in understanding protein evolution and design.

## Abstract

Proteins are a matter of dual nature. As a physical object, a protein molecule is a folded chain of amino acids with multifarious biochemistry. But it is also an instantiation along an evolutionary trajectory determined by the function performed by the protein within a hierarchy of interwoven interaction networks of the cell, the organism and the population. A physical theory of proteins therefore needs to unify both aspects, the biophysical and the evolutionary. Specifically, it should provide a model of how the DNA gene is mapped into the functional phenotype of the protein. We review several physical approaches to the protein problem, focusing on a mechanical framework which treats proteins as evolvable condensed matter: Mutations introduce localized perturbations in the gene, which are translated to localized perturbations in the protein matter. A natural tool to examine how mutations shape the phenotype are Green's functions. They map the evolutionary linkage among mutations in the gene (termed epistasis) to cooperative physical interactions among the amino acids in the protein. We discuss how the mechanistic view can be applied to examine basic questions of protein evolution and design.