A minimum set of stable blocks for rational design of polypeptide chains Running head: A set of stable blocks for protein rational design

TL;DR

This study identifies a minimal set of stable pentapeptides that can form the foundational structures necessary for designing polypeptides with specific 3D conformations, aiding in protein engineering.

Contribution

It introduces a minimal set of stable pentapeptide blocks with diverse topologies, facilitating rational protein design based on stable conformations.

Findings

Identified 1,225 stable pentapeptides over 80% of simulation time.

Clustered into 54 topological types related to secondary structures.

Provided a complete set of conformationally stable blocks for protein design.

Abstract

The aim of this work was to find a minimal set of structurally stable pentapeptides, which allows forming a polypeptide chain of a required 3D structure. To search for factors that ensure structural stability of the pentapeptide, we generated peptide sequences with no more than three functional groups, based on the alanine pentapeptide AAAAA. We analyzed 44,860 structures of peptides by the molecular dynamics method and found that 1,225 pentapeptides over 80% of the simulation time were in a stable conformation. Clustering of these conformations revealed 54 topological types of conformationally stable pentapeptides. These conformations relate to different combined elements of the protein secondary structure. So, we obtained a minimal set of amino acid structures of conformationally stable pentapeptides, creating a complete set of different topologies that ensure the formation of pre-folded conformation of protein structures.