Method for Computing Protein Binding Affinity

TL;DR

This paper introduces a Monte Carlo computational method to accurately estimate the free energy of ligand-protein binding by extending configuration space and enabling state transitions, given known structures and force fields.

Contribution

It presents a novel Monte Carlo approach that incorporates a discrete variable and specialized moves to compute binding affinity quantitatively.

Findings

Provides a quantitative estimate of binding free energy.

Requires accurate protein structure and force field.

Enables transition between bound and unbound states.

Abstract

A Monte Carlo method is given to compute the binding affinity of a ligand to a protein. The method involves extending configuration space by a discrete variable indicating whether the ligand is bound to the protein and a special Monte Carlo move which allows transitions between the unbound and bound states. Provided that an accurate protein structure is given, that the protein-ligand binding site is known, and that an accurate chemical force field together with a continuum solvation model is used, this method provides a quantitative estimate of the free energy of binding.