ArticleBiomolecules2022
The Epigenetic Dimension of Protein Structure Is an Intrinsic Weakness of the AlphaFold Program.
Article in Biomolecules, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- The perineurium integrates leptin with its sympathetic outflow to protect against obesity.Nature metabolism · 2026Article
- Origin and Evolution of Very Large Extracellular Proteins in Fructophilic Lactic Acid Bacteria.Genome biology and evolution · 2026Article
- Serotonergic Signaling Rewired: A Lipid Raft-Controlled Model of Synaptic Transmission Grounded in the Fundamental Parameters of Biological Systems.Life (Basel, Switzerland) · 2026Article
- Cannabinoid GPCRs, ectopic olfactory GPCRs and TRP channels: a prespecified baseline-edit-rescue framework for testing higher-order membrane-conditioned integration.Biology methods & protocols · 2026Article
- Role and Potential of Artificial Intelligence in Biomarker Discovery and Development of Treatment Strategies for Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2025Review
- AlphaFold2, SPINE-X, and Seder on Four Hard CASP Targets.Methods in molecular biology (Clifton, N.J.) · 2025Article
- TBM preferred to AlphaFold 3 for functional models of insect odorant receptors.Computational and structural biotechnology journal · 2025Article
- Advancing Membrane-Associated Protein Docking with Improved Sampling and Scoring in Rosetta.Journal of chemical theory and computation · 2024Article
- Insights into AlphaFold's breakthrough in neurodegenerative diseases.Irish journal of medical science · 2024Review
- The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins.Nature chemical biology · 2024Review
- Advancing membrane-associated protein docking with improved sampling and scoring in Rosetta.bioRxiv : the preprint server for biology · 2024Article
- AlphaFold2 as a replacement for solution NMR structure determination of small proteins: Not so fast!Journal of magnetic resonance (San Diego, Calif. : 1997) · 2024Article
- Inferring molecular inhibition potency with AlphaFold predicted structures.Scientific reports · 2024Article
- What Is life? Rethinking Biology in Light of Fundamental Parameters.Life (Basel, Switzerland) · 2024Review
- Predictive Modeling of Proteins Encoded by a Plant Virus Sheds a New Light on Their Structure and Inherent Multifunctionality.Biomolecules · 2024Article
- Tld1 is a regulator of triglyceride lipolysis that demarcates a lipid droplet subpopulation.The Journal of cell biology · 2024Article
- Conformational analysis of the IQSEC2 protein by statistical thermodynamics.Current research in structural biology · 2024Article
- Exploring the World of Membrane Proteins: Techniques and Methods for Understanding Structure, Function, and Dynamics.Molecules (Basel, Switzerland) · 2023Review
- Revolutionizing Medicinal Chemistry: The Application of Artificial Intelligence (AI) in Early Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Lipid rafts and human diseases: why we need to target gangliosides.FEBS open bio · 2023Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One of the most important lessons we have learned from sequencing the human genome is that not all proteins have a 3D structure. In fact, a large part of the human proteome is made up of intrinsically disordered proteins (IDPs) which can adopt multiple structures, and therefore, multiple functions, depending on the ligands with which they interact. Under these conditions, one can wonder about the value of algorithms developed for predicting the structure of proteins, in particular AlphaFold, an AI which claims to have solved the problem of protein structure. In a recent study, we highlighted a particular weakness of AlphaFold for membrane proteins. Based on this observation, we have proposed a paradigm, referred to as "Epigenetic Dimension of Protein Structure" (EDPS), which takes into account all environmental parameters that control the structure of a protein beyond the amino acid sequence (hence "epigenetic"). In this new study, we compare the reliability of the AlphaFold and Robetta algorithms' predictions for a new set of membrane proteins involved in human pathologies. We found that Robetta was generally more accurate than AlphaFold for ascribing a membrane-compatible topology. Raft lipids (e.g., gangliosides), which control the structural dynamics of membrane protein structure through chaperone effects, were identified as major actors of the EDPS paradigm. We conclude that the epigenetic dimension of a protein structure is an intrinsic weakness of AI-based protein structure prediction, especially AlphaFold, which warrants further development.
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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 Socratic graph.