Identifying and Overcoming the Sampling Challenges in Relative Binding Free Energy Calculations of a Model Protein:Protein Complex

• Published in: Journal of chemical theory and computation Vol. 19; no. 15; pp. 4863 - 4882
• Main Authors: Zhang, Ivy, Rufa, Dominic A., Pulido, Iván, Henry, Michael M., Rosen, Laura E., Hauser, Kevin, Singh, Sukrit, Chodera, John D.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 08.08.2023
• Subjects: Affinity; Amino Acids; Binding; Binding energy; Entropy; Free energy; Graphics processing units; Molecular Dynamics Simulation; Mutation; Protein Binding; Proteins; Sampling; Statistical Mechanics; Thermodynamics; Workflow

Relative alchemical binding free energy calculations are routinely used in drug discovery projects to optimize the affinity of small molecules for their drug targets. Alchemical methods can also be used to estimate the impact of amino acid mutations on protein:protein binding affinities, but these c...