ArticleBiophysical journal2020
Improving the Accuracy of Protein Thermostability Predictions for Single Point Mutations.
Article in Biophysical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Accelerated Combinatorial Drug Design for Human Immunodeficiency Virus Resistance through Seeded Multisite λ-Dynamics.Journal of chemical theory and computation · 2026Article
- Protein folding stability estimation with explicit consideration of unfolded states.Nature communications · 2026Article
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- Antibody Affinity Maturation by Computational Design.Methods in molecular biology (Clifton, N.J.) · 2026Article
- ΦX174 bacteriophage viability predicted by protein biophysical modeling.bioRxiv : the preprint server for biology · 2025Article
- Predicting side chain conformations in folded proteins by AlphaFold: Perspective and challenges.Biophysical journal · 2025Article
- Benchmarking Free Energy Calculations: Analysis of Single and Double Mutations Across Two Simulation Software Platforms for Two Protein Systems.bioRxiv : the preprint server for biology · 2025Article
- Predicting Thermodynamic Stability at Protein G Sites with Deleterious Mutations Using λ-Dynamics with Competitive Screening.The journal of physical chemistry letters · 2025Article
- Using AlphaFold2 to Predict the Conformations of Side Chains in Folded Proteins.bioRxiv : the preprint server for biology · 2025Article
- Ligand and Residue Free Energy Perturbations Solve the Dual Binding Mode Proposal for an AThe journal of physical chemistry. B · 2025Article
- ProstaNet: A Novel Geometric Vector Perceptrons-Graph Neural Network Algorithm for Protein Stability Prediction in Single- and Multiple-Point Mutations with Experimental Validation.Research (Washington, D.C.) · 2025Article
- Engineering miniature IscB nickase for robust base editing with broad targeting range.Nature chemical biology · 2024Article
- ThermoLink: Bridging disulfide bonds and enzyme thermostability through database construction and machine learning prediction.Protein science : a publication of the Protein Society · 2024Article
- Robust Prediction of Relative Binding Energies for Protein-Protein Complex Mutations Using Free Energy Perturbation Calculations.Journal of molecular biology · 2024Article
- How to Sample Dozens of Substitutions per Site with λ Dynamics.Journal of chemical theory and computation · 2024Article
- Robust prediction of relative binding energies for protein-protein complex mutations using free energy perturbation calculations.bioRxiv : the preprint server for biology · 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
- Selection pressures on evolution of ribonuclease H explored with rigorous free-energy-based design.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Assessing variants of uncertain significance implicated in hearing loss using a comprehensive deafness proteome.Human genetics · 2023Article
- Mutation bias and the predictability of evolution.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accurately predicting the protein thermostability changes upon single point mutations in silico is a challenge that has implications for understanding diseases as well as industrial applications of protein engineering. Free energy perturbation (FEP) has been applied to predict the effect of single point mutations on protein stability for over 40 years and emerged as a potentially reliable prediction method with reasonable throughput. However, applications of FEP in protein stability calculations in industrial settings have been hindered by a number of limitations, including the inability to model mutations to and from prolines in which the bonded topology of the backbone is modified and the complexity in modeling charge-changing mutations. In this study, we have extended the FEP+ protocol to enable the accurate modeling of the effects on protein stability from proline mutations and from charge-changing mutations. We also evaluated the influence of the unfolded model in the stability calculations using increasingly longer peptides with native sequence and conformations. With the abovementioned improvements, the accuracy of FEP predictions of protein stability over a data set of 87 mutations on five different proteins has drastically improved compared with previous studies, with a mean unsigned error of 0.86 kcal/mol and root mean square error of 1.11 kcal/mol, comparable with the accuracy of previously published state-of-the-art small-molecule relative binding affinity calculations, which have been shown to be capable of driving discovery projects.
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