Protein design in a lattice model of hydrophobic and polar amino acids

TL;DR

This paper presents a new inverse design method for amino acid sequences on lattice structures, successfully creating sequences with desired native states and exploring competing conformations.

Contribution

It introduces an improved inverse design strategy for hydrophobic-polar amino acid sequences on 3D lattice models, achieving consistent success in sequence design.

Findings

Design procedure succeeded in all tested cases

Explored conformations that compete with target structures

Improved success rate over previous Monte-Carlo methods

Abstract

A general strategy is described for finding which amino acid sequences have native states in a desired conformation (inverse design). The approach is used to design sequences of 48 hydrophobic and polar aminoacids on three-dimensional lattice structures. Previous studies employing a sequence-space Monte-Carlo technique resulted in the successful design of one sequence in ten attempts. The present work also entails the exploration of conformations that compete significantly with the target structure for being its ground state. The design procedure is successful in all the ten cases.