Paper List
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Autonomous Agents Coordinating Distributed Discovery Through Emergent Artifact Exchange
This paper addresses the fundamental limitation of current AI-assisted scientific research by enabling truly autonomous, decentralized investigation w...
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D-MEM: Dopamine-Gated Agentic Memory via Reward Prediction Error Routing
This paper addresses the fundamental scalability bottleneck in LLM agentic memory systems: the O(N²) computational complexity and unbounded API token ...
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Countershading coloration in blue shark skin emerges from hierarchically organized and spatially tuned photonic architectures inside skin denticles
This paper solves the core problem of how blue sharks achieve their striking dorsoventral countershading camouflage, revealing that coloration origina...
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Human-like Object Grouping in Self-supervised Vision Transformers
This paper addresses the core challenge of quantifying how well self-supervised vision models capture human-like object grouping in natural scenes, br...
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Hierarchical pp-Adic Framework for Gene Regulatory Networks: Theory and Stability Analysis
This paper addresses the core challenge of mathematically capturing the inherent hierarchical organization and multi-scale stability of gene regulator...
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Towards unified brain-to-text decoding across speech production and perception
This paper addresses the core challenge of developing a unified brain-to-text decoding framework that works across both speech production and percepti...
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Dual-Laws Model for a theory of artificial consciousness
This paper addresses the core challenge of developing a comprehensive, testable theory of consciousness that bridges biological and artificial systems...
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Pulse desynchronization of neural populations by targeting the centroid of the limit cycle in phase space
This work addresses the core challenge of determining optimal pulse timing and intensity for desynchronizing pathological neural oscillations when the...
Topological Enhancement of Protein Kinetic Stability
BioISI – Instituto de Biossistemas e Ciências Integrativas and Departamento de Física, Faculdade de Ciências, Universidade de Lisboa, 1749-016, Lisboa, Portugal
30秒速读
IN SHORT: This work addresses the long-standing puzzle of why knotted proteins exist by demonstrating that deep knots provide a functional advantage through enhanced kinetic stability, not equilibrium thermodynamics.
核心创新
- Methodology Introduces a controlled computational framework (LTyP vs. non-LTyP Monte Carlo simulations) to isolate the pure topological effect of knots from sequence, structure, and energetic contributions.
- Biology Reveals a strong, asymmetric dependence on knot depth: deep knots (e.g., YibK) suppress unfolding transitions by >1 order of magnitude, dramatically enhancing kinetic stability, while shallow knots have minimal effect.
- Theory Integrates a reverse evolution model, showing that kinetic stabilization is sequence-dependent, emerging fully only with increased amino acid alphabet complexity, providing an evolutionary rationale for knotted protein conservation.
主要结论
- Deep protein knots (e.g., YibK) enhance kinetic stability (resistance to unfolding) by more than an order of magnitude compared to topology-breaking controls, while shallow knots show minimal effect.
- Kinetic stability increases sharply with knot depth, whereas foldability is only moderately affected, revealing an asymmetric topological constraint favoring native state persistence.
- Kinetic stabilization is sequence-dependent: early, low-complexity (10-letter alphabet) sequences exhibit weaker resistance to unfolding, with stabilization becoming pronounced only with modern (20-letter) alphabet complexity.
摘要: Knotted proteins embed a physical (i.e., open) knot within their native structures. For decades, significant effort has been devoted to elucidating the functional role of knots in proteins, yet no consensus has been reached. Here, using extensive Monte Carlo off-lattice simulations of a simple structure-based model, we isolate the effect of topology by comparing simulations that preserve the linear topology of the chain with simulations that allow chain crossings. This controlled framework enables us to isolate topological effects from sequence, structure and energetic contributions. We show that protein kinetic stability, defined as resistance to unfolding at a fixed temperature, is higher in knotted proteins. Additionally, kinetic stability increases significantly with knot depth, whereas foldability (or folding efficiency) is comparatively less affected. By considering a simple model of protein evolution in which amino-acid alphabet size is used as a proxy for evolutionary time, we find that increasing primary-sequence complexity through the addition of biotic amino acids predominantly enhances kinetic stability. Taken together, these results indicate that kinetic stability is a functional advantage conferred by protein knots and suggest that evolutionary pressure for kinetic stability could contribute to the persistence of knotted proteins.