ArticleJournal of molecular biology2019
Relative Binding Affinity Prediction of Charge-Changing Sequence Mutations with FEP in Protein-Protein Interfaces.
Article in Journal of molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed.
- A Functional Investigation of Antibody Fc-FcRn Variant Binding Guided by In Silico Free Energy Perturbation Methods.Journal of molecular biology · 2026Article
- Toward Relative Redox Potential Predictions in Flavoproteins: Treatment of a Charge-Changing Mutation in Alchemical Free Energy Simulations.Journal of chemical theory and computation · 2026Article
- MAHLER: Integrating Metadynamics and Inverse Folding to Predict Antibody-Antigen Kinetics.bioRxiv : the preprint server for biology · 2026Article
- A functional investigation of antibody Fc-FcRn variant binding guided bybioRxiv : the preprint server for biology · 2026Article
- Antibody Affinity Maturation by Computational Design.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Review
- Accurate Prediction of Protein Tertiary and Quaternary Stability Using Fine-Tuned Protein Language Models and Free Energy Perturbation.International journal of molecular sciences · 2025Article
- Multiscale Computational Protocols for Accurate Residue Interactions at the Flexible Insulin-Receptor Interface.Journal of chemical information and modeling · 2025Article
- Rational selection of the monoclonal α-synuclein antibody amlenetug (Lu AF82422) for the treatment of α-synucleinopathies.NPJ Parkinson's disease · 2025Article
- Modulating the Kinetics of a Fluorescence Anisotropy Immunoassay Using Tracer Point Mutations to Measure Human C-Peptide Secretion On-Chip.ACS omega · 2025Article
- Decoding the blueprint of receptor binding by filoviruses through large-scale binding assays and machine learning.Cell host & microbe · 2025Article
- Binding Selectivity Analysis from Alchemical Receptor Hopping and Swapping Free Energy Calculations.The journal of physical chemistry. B · 2024Article
- A Method for Treating Significant Conformational Changes in Alchemical Free Energy Simulations of Protein-Ligand Binding.Journal of chemical theory and computation · 2024Article
- Robust Prediction of Relative Binding Energies for Protein-Protein Complex Mutations Using Free Energy Perturbation Calculations.Journal of molecular biology · 2024Article
- Understanding the impact of binding free energy and kinetics calculations in modern drug discovery.Expert opinion on drug discovery · 2024Review
- Article
- Robust prediction of relative binding energies for protein-protein complex mutations using free energy perturbation calculations.bioRxiv : the preprint server for biology · 2024Article
- Application of an alchemical free energy method for the prediction of thermostable DuraPETase variants.Applied microbiology and biotechnology · 2024Article
- Potts Hamiltonian Models and Molecular Dynamics Free Energy Simulations for Predicting the Impact of Mutations on Protein Kinase Stability.The journal of physical chemistry. B · 2024Article
- Enhanced Sampling of Buried Charges in Free Energy Calculations Using Replica Exchange with Charge Tempering.Journal of chemical theory and computation · 2024Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Building on the substantial progress that has been made in using free energy perturbation (FEP) methods to predict the relative binding affinities of small molecule ligands to proteins, we have previously shown that results of similar quality can be obtained in predicting the effect of mutations on the binding affinity of protein-protein complexes. However, these results were restricted to mutations which did not change the net charge of the side chains due to known difficulties with modeling perturbations involving a change in charge in FEP. Various methods have been proposed to address this problem. Here we apply the co-alchemical water approach to study the efficacy of FEP calculations of charge changing mutations at the protein-protein interface for the antibody-gp120 system investigated previously and three additional complexes. We achieve an overall root mean square error of 1.2 kcal/mol on a set of 106 cases involving a change in net charge selected by a simple suitability filter using side-chain predictions and solvent accessible surface area to be relevant to a biologic optimization project. Reasonable, although less precise, results are also obtained for the 44 more challenging mutations that involve buried residues, which may in some cases require substantial reorganization of the local protein structure, which can extend beyond the scope of a typical FEP simulation. We believe that the proposed prediction protocol will be of sufficient efficiency and accuracy to guide protein engineering projects for which optimization and/or maintenance of a high degree of binding affinity is a key objective.
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