Variational approach to protein design and extraction of interaction potentials

TL;DR

This paper introduces a variational method for protein design that simultaneously extracts amino acid interaction potentials and sequence free energies, offering a straightforward approach applicable to realistic off-lattice proteins.

Contribution

It presents a novel variational framework for direct and inverse protein folding, avoiding complex threading procedures and validated through lattice model tests.

Findings

Effective extraction of amino acid interaction potentials.

Validates approach with rigorous lattice model tests.

Simplifies protein design computations.

Abstract

We present and discuss a novel approach to the direct and inverse protein folding problem. The proposed strategy is based on a variational approach that allows the simultaneous extraction of amino acid interactions and the low-temperature free energy of sequences of amino acids. The knowledge-based technique is simple and straightforward to implement even for realistic off-lattice proteins because it does not entail threading-like procedures. Its validity is assessed in the context of a lattice model by means of a variety of stringent checks.