A new study has deciphered why the core of folded proteins exhibits a consistent packing density, regardless of protein size or family. Researchers found that the backbone of the protein chain itself, and not just the side chains, plays a crucial role in dictating this density. Specifically, the rigid geometry of peptide bonds, combined with the preference for certain dihedral angles, limits the possible arrangements and leads to a universally dense core. This discovery resolves a long-standing puzzle in protein folding and offers a deeper understanding of protein structure and stability.
The post "Limits of Smart: Molecules and Chaos" argues that relying solely on "smart" systems, particularly AI, for complex problem-solving has inherent limitations. It uses the analogy of protein folding to illustrate how brute-force computational approaches, even with advanced algorithms, struggle with the sheer combinatorial explosion of possibilities in systems governed by physical laws. While AI excels at specific tasks within defined boundaries, it falters when faced with the chaotic, unpredictable nature of reality at the molecular level. The post suggests that a more effective approach involves embracing the inherent randomness and exploring "dumb" methods, like directed evolution in biology, which leverage natural processes to navigate complex landscapes and discover solutions that purely computational methods might miss.
HN commenters largely agree with the premise of the article, pointing out that intelligence and planning often fail in complex, chaotic systems like biology and markets. Some argue that "smart" interventions can exacerbate problems by creating unintended consequences and disrupting natural feedback loops. Several commenters suggest that focusing on robustness and resilience, rather than optimization for a specific outcome, is a more effective approach in such systems. Others discuss the importance of understanding limitations and accepting that some degree of chaos is inevitable. The idea of "tinkering" and iterative experimentation, rather than grand plans, is also presented as a more realistic and adaptable strategy. A few comments offer specific examples of where "smart" interventions have failed, like the use of pesticides leading to resistant insects or financial engineering contributing to market instability.
A cell's metabolic state, meaning the chemical reactions happening within it, significantly influences its fate, including whether it divides, differentiates into a specialized cell type, or dies. Rather than simply fueling cellular processes, metabolism actively shapes cell behavior by altering gene expression and protein function. Specific metabolites, the intermediate products of metabolism, can directly modify proteins, impacting their activity and guiding cellular decisions. This understanding opens up possibilities for manipulating metabolism to control cell fate, offering potential therapeutic interventions for diseases like cancer.
HN commenters generally expressed fascination with the article's findings on how metabolism influences cell fate. Several highlighted the counterintuitive nature of the discovery, noting that it shifts the traditional understanding of DNA as the primary driver of cellular differentiation. Some discussed the implications for cancer research, regenerative medicine, and aging. One commenter pointed out the potential connection to the Warburg effect, where cancer cells favor glycolysis even in the presence of oxygen. Another questioned the generalizability of the findings, given the focus on yeast and mouse embryonic stem cells. A few expressed excitement about the future research directions this opens up, particularly regarding metabolic interventions for disease.
A new study reveals a shared mechanism for coping with environmental stress in plants and green algae dating back 600 million years to their common ancestor. Researchers found that both plants and algae utilize a protein called CONSTANS, originally known for its role in flowering, to manage responses to various stresses like drought and high salinity. This ancient stress response system involves CONSTANS interacting with other proteins to regulate gene expression, protecting the organism from damage. This discovery highlights a highly conserved and essential survival mechanism across the plant kingdom and offers potential insights into improving stress tolerance in crops.
HN commenters discuss the implications of the study showing a shared stress response across algae and plants, questioning whether this truly represents 600 million years of conservation or if horizontal gene transfer played a role. Some highlight the importance of understanding these mechanisms for improving crop resilience in the face of climate change. Others express skepticism about the specific timeline presented, suggesting further research is needed to solidify the evolutionary narrative. The potential for biotechnological applications, such as engineering stress tolerance in crops, is also a point of interest. A few users dive into the specifics of the abscisic acid (ABA) pathway discussed in the study, pointing out its known role in stress response and questioning the novelty of the findings. Overall, the comments demonstrate a mix of intrigue, cautious interpretation, and a focus on the practical implications for agriculture and biotechnology.
This study reveals a novel regulatory mechanism in gene expression involving tRNA introns. Researchers demonstrate that spliced and released tRNA introns, specifically from tRNA-Leu(CAA), can base-pair with complementary sequences in the 5' untranslated regions (5'UTRs) of mRNAs. This interaction hinders the binding of the small ribosomal subunit (40S) to the mRNA, thereby repressing translation. This repression is specific and dependent on the complementarity between the intron and the 5'UTR, with mutations disrupting base-pairing abolishing the inhibitory effect. These findings highlight a previously unknown function for tRNA introns as sequence-specific post-transcriptional regulators of gene expression.
HN users discuss the potential impact of the research, with some expressing excitement about the discovery of tRNA fragments regulating gene expression and its implications for synthetic biology and disease treatment. Others raise questions about the generalizability of the findings, noting the study's focus on specific yeast tRNA and mRNA pairings and wondering how widespread this regulatory mechanism is across different organisms and conditions. Some commenters also point out the complexity of cellular processes, highlighting the existing knowledge of tRNA involvement in various functions and emphasizing that this new regulatory mechanism adds another layer to this complexity. A few users delve into technical aspects, such as the methodology used in the research and its potential limitations.
The "Third Base" article explores the complex role of guanine quadruplexes (G4s), four-stranded DNA structures, in biology. Initially dismissed as lab artifacts, G4s are now recognized as potentially crucial elements in cellular processes. They are found in telomeres and promoter regions of genes, suggesting roles in aging and gene expression. The article highlights the dynamic nature of G4 formation and how it can be influenced by proteins and small molecules. While research is ongoing, G4s are implicated in both vital functions and diseases like cancer, raising the possibility of targeting them for therapeutic interventions.
Hacker News users discuss the surprisingly complex history and evolution of third base in baseball. Several commenters highlight the article's insightful explanation of how the base's positioning has changed over time, influenced by factors like foul territory rules and the gradual shift from a "bound catch" rule to the modern fly catch. Some express fascination with the now-obsolete "three strikes and you're out if it's caught on the first bounce" rule. Others appreciate the detailed descriptions of early baseball and how the different rules shaped the way the game was played. A few commenters draw parallels between the evolution of baseball and the development of other sports and games, emphasizing how seemingly arbitrary rules can have significant impacts on strategy and gameplay. There is general appreciation for the depth of research and clear writing style of the article.
Summary of Comments ( 18 )
https://news.ycombinator.com/item?id=43681132
HN users discuss the implications of the protein folding research, with some expressing skepticism about the "mystery solved" claim. Several commenters highlight that the study focuses on a simplified model and question its applicability to real-world protein folding complexity. There's debate about the significance of the findings, with some arguing it's an incremental step rather than a major breakthrough. A few users delve into the technical details of the research, discussing the role of hydrophobic interactions and the limitations of current computational models. Others question the practical applications of the research, wondering if it will lead to advancements in areas like drug discovery. Overall, the comments reflect a cautious optimism tempered by a recognition of the inherent complexity of protein folding.
The Hacker News thread discussing the protein folding research has a moderate number of comments, exploring various aspects of the findings and their implications.
Several commenters express enthusiasm for the research, viewing it as a significant step in understanding protein structure and function. They highlight the importance of packing density within protein cores and how this research sheds light on a previously unexplained phenomenon. The elegance and simplicity of the explanation are also praised, with some noting that it's a reminder that complex biological processes can sometimes have straightforward underlying principles.
A recurring theme is the potential impact of this discovery on protein engineering and drug design. Commenters speculate on how a deeper understanding of core packing could lead to more efficient methods for designing proteins with specific properties, including novel therapeutics and industrial enzymes.
Some commenters delve into the technical details of the research, discussing the methods used and the implications of the findings for related fields like computational biology and biophysics. There's a discussion about the role of hydrophobic interactions in protein folding and how this research contributes to that understanding.
A few commenters express a degree of caution, pointing out that while the research is promising, it's still early days. They emphasize the need for further research to validate the findings and explore their broader applicability. One commenter questions whether the model is truly universal or if it applies only to certain classes of proteins.
There's also a brief discussion about the accessibility of the original research paper. Some express disappointment that it's behind a paywall, limiting access for those outside of academic institutions.
Finally, a couple of commenters draw connections to other scientific fields, highlighting the interconnectedness of scientific disciplines and how discoveries in one area can inform and inspire research in others. They mention related work in materials science and nanotechnology. One comment humorously links the research to the efficient packing of groceries in a bag.