Proteins are the workhorses of life, performing nearly every cellular task. To function, they must fold into precise 3D shapes—a process guided by their amino acid sequences. But how proteins fold remains a hot topic in science, with huge implications for health and medicine.
⚙️ The Basics of Protein Folding:
Why it matters: Proteins fold to become functional. Misfolding can lead to toxic aggregates, linked to diseases like Alzheimer’s, Parkinson’s, and amyloidosis.
Traditional View: Proteins spontaneously fold into their lowest-energy states (thermodynamic hypothesis).
Chaperones: Special cellular machines assist proteins in folding correctly, preventing misfolding and aggregation.
🧠 Two Views in Debate:
1. Shimanovich & Hartl (2024):
Argue that thermodynamics guides folding: proteins seek their most stable, low-energy configuration.
Highlight the success of AI tools like #AlphaFold, which accurately predict protein shapes.
Applications: Understanding cancer proteins, designing drugs, and unraveling viral mechanisms like COVID-19.
2. Sorokina et al. (2022):
Challenge the thermodynamic model, suggesting folding is an active, energy-dependent process, relying on cellular machinery.
Argue that many proteins cannot fold spontaneously, especially in a living cell's crowded, complex environment.
Applications: Could reshape our understanding of neurodegenerative diseases and lead to novel therapeutic targets.
🌍 Why It Matters for Health:
Disease Insights: Misfolding diseases like Alzheimer’s might involve disrupted folding machinery, not just missteps in energy minimization.
Drug Development: Rethinking folding as energy-driven could lead to new ways to stabilize proteins or prevent toxic aggregates.
Biotech Innovation: Advances in AI and understanding folding mechanisms could improve protein engineering for vaccines, enzymes, and treatments.
💡 The Big Question:
Is protein folding a passive search for stability, or does it require the cell’s active intervention? The answer could redefine biology and medicine.
What’s your take on this debate? 👇
Sorokina, I., A.R. Mushegian, and E.V. Koonin, Is Protein Folding a Thermodynamically Unfavorable, Active, Energy-Dependent Process? Int J Mol Sci, 2022. 23(1).
Shimanovich, U., & Hartl, F. U. (2024). Protein folding: From physico-chemical rules and cellular machineries of protein quality control to AI solutions. Proceedings of the National Academy of Sciences, 121(34), e2411135121. https://doi.org/doi:10.1073/pnas.2411135121
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