The article by Christopher M. Dobson discusses the structural basis of protein folding and its links with human disease. Protein folding is a critical process where proteins fold into their functional states after synthesis, and recent advancements have revealed that this process is stochastic but biased towards native-like interactions. However, under certain conditions, proteins fail to fold correctly or remain folded, leading to a range of diseases, particularly amyloidoses such as Alzheimer's and prion diseases. The formation of amyloid fibrils, which are highly organized aggregates of proteins, is a generic property of polypeptides and not limited to specific pathological conditions. Dobson's research on lysozyme has shown that amyloid fibrils can form from partially folded intermediates, and the stability of the native state is crucial in preventing this process. The generic nature of amyloid structure suggests that the inherent propensity for proteins to aggregate is a primary issue that living systems must control. Molecular chaperones and the evolution of sequences that form cooperative globular structures are key mechanisms in avoiding aggregation. The formation of amyloid fibrils does not violate the hypothesis that a protein sequence codes for a single fold, as the amyloid structure is not coded for by the sequence but formed through interactions involving the polypeptide backbone. Understanding these mechanisms can provide insights into the prevention and treatment of amyloid diseases.The article by Christopher M. Dobson discusses the structural basis of protein folding and its links with human disease. Protein folding is a critical process where proteins fold into their functional states after synthesis, and recent advancements have revealed that this process is stochastic but biased towards native-like interactions. However, under certain conditions, proteins fail to fold correctly or remain folded, leading to a range of diseases, particularly amyloidoses such as Alzheimer's and prion diseases. The formation of amyloid fibrils, which are highly organized aggregates of proteins, is a generic property of polypeptides and not limited to specific pathological conditions. Dobson's research on lysozyme has shown that amyloid fibrils can form from partially folded intermediates, and the stability of the native state is crucial in preventing this process. The generic nature of amyloid structure suggests that the inherent propensity for proteins to aggregate is a primary issue that living systems must control. Molecular chaperones and the evolution of sequences that form cooperative globular structures are key mechanisms in avoiding aggregation. The formation of amyloid fibrils does not violate the hypothesis that a protein sequence codes for a single fold, as the amyloid structure is not coded for by the sequence but formed through interactions involving the polypeptide backbone. Understanding these mechanisms can provide insights into the prevention and treatment of amyloid diseases.