A Deterministic Approach to the Protein Design Problem

TL;DR

This paper presents a deterministic analytical method for protein design using contact energy models, enabling the creation of stable amino acid sequences and comparing them with real proteins to validate the approach.

Contribution

It introduces a novel analytical prescription for designing stable protein sequences based on a simplified contact energy model, improving understanding of sequence-structure relationships.

Findings

Designed sequences show good correspondence with real proteins

Analytical method effectively predicts stable amino acid arrangements

Discrepancies in energy fitting affect prediction accuracy

Abstract

We have considered the problem of protein design based on a model where the contact energy between amino acid residues is fitted phenomenologically using the Miyazawa--Jernigan matrix. Due to the simple form of the contact energy function, an analytical prescription is found which allows us to design energetically stable sequences for fixed amino acid residues compositions and target structures. The theoretically obtained sequences are compared with real proteins and good correspondence is obtained. Finally we discuss the effect of discrepancies in the procedure used to fit the contact energy on our theoretical predictions.