ArticleBiochemistry2016
Documentation of an Imperative To Improve Methods for Predicting Membrane Protein Stability.
Article in Biochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- A small molecule stabilizer rescues the surface expression of nearly all missense variants in a GPCR.Nature structural & molecular biology · 2025Article
- Design principles of the common Gly-X6-Gly membrane protein building block.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- De novo-designed transmembrane proteins bind and regulate a cytokine receptor.Nature chemical biology · 2024Article
- Machine learning in computational modelling of membrane protein sequences and structures: From methodologies to applications.Computational and structural biotechnology journal · 2023Review
- Functional genomics of OCTN2 variants informs protein-specific variant effect predictor for Carnitine Transporter Deficiency.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Towards generalizable predictions for G protein-coupled receptor variant expression.Biophysical journal · 2022Article
- Predicting the functional impact of KCNQ1 variants with artificial neural networks.PLoS computational biology · 2022Article
- Article
- Diverse Scientific Benchmarks for Implicit Membrane Energy Functions.Journal of chemical theory and computation · 2021Article
- Membrane Protein Engineering with Rosetta.Methods in molecular biology (Clifton, N.J.) · 2021Article
- mCSM-membrane: predicting the effects of mutations on transmembrane proteins.Nucleic acids research · 2020Article
- Macromolecular modeling and design in Rosetta: recent methods and frameworks.Nature methods · 2020Review
- Protein Structure Prediction and Design in a Biologically Realistic Implicit Membrane.Biophysical journal · 2020Article
- Backbone Hydrogen Bond Energies in Membrane Proteins Are Insensitive to Large Changes in Local Water Concentration.Journal of the American Chemical Society · 2020Article
- Probing biophysical sequence constraints within the transmembrane domains of rhodopsin by deep mutational scanning.Science advances · 2020Article
- Assessment of software methods for estimating protein-protein relative binding affinities.PloS one · 2020Article
- Predicting changes in protein stability caused by mutation using sequence-and structure-based methods in a CAGI5 blind challenge.Human mutation · 2019Article
- Biophysical and Mechanistic Models for Disease-Causing Protein Variants.Trends in biochemical sciences · 2019Review
- Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis.Chemical reviews · 2019Article
- Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
There is a compelling and growing need to accurately predict the impact of amino acid mutations on protein stability for problems in personalized medicine and other applications. Here the ability of 10 computational tools to accurately predict mutation-induced perturbation of folding stability (ΔΔG) for membrane proteins of known structure was assessed. All methods for predicting ΔΔG values performed significantly worse when applied to membrane proteins than when applied to soluble proteins, yielding estimated concordance, Pearson, and Spearman correlation coefficients of <0.4 for membrane proteins. Rosetta and PROVEAN showed a modest ability to classify mutations as destabilizing (ΔΔG < -0.5 kcal/mol), with a 7 in 10 chance of correctly discriminating a randomly chosen destabilizing variant from a randomly chosen stabilizing variant. However, even this performance is significantly worse than for soluble proteins. This study highlights the need for further development of reliable and reproducible methods for predicting thermodynamic folding stability in membrane proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.