Paper List
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Ill-Conditioning in Dictionary-Based Dynamic-Equation Learning: A Systems Biology Case Study
This paper addresses the critical challenge of numerical ill-conditioning and multicollinearity in library-based sparse regression methods (e.g., SIND...
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Hybrid eTFCE–GRF: Exact Cluster-Size Retrieval with Analytical pp-Values for Voxel-Based Morphometry
This paper addresses the computational bottleneck in voxel-based neuroimaging analysis by providing a method that delivers exact cluster-size retrieva...
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abx_amr_simulator: A simulation environment for antibiotic prescribing policy optimization under antimicrobial resistance
This paper addresses the critical challenge of quantitatively evaluating antibiotic prescribing policies under realistic uncertainty and partial obser...
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PesTwin: a biology-informed Digital Twin for enabling precision farming
This paper addresses the critical bottleneck in precision agriculture: the inability to accurately forecast pest outbreaks in real-time, leading to su...
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Equivariant Asynchronous Diffusion: An Adaptive Denoising Schedule for Accelerated Molecular Conformation Generation
This paper addresses the core challenge of generating physically plausible 3D molecular structures by bridging the gap between autoregressive methods ...
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Omics Data Discovery Agents
This paper addresses the core challenge of making published omics data computationally reusable by automating the extraction, quantification, and inte...
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Single-cell directional sensing at ultra-low chemoattractant concentrations from extreme first-passage events
This work addresses the core challenge of how a cell can rapidly and accurately determine the direction of a chemoattractant source when the signal is...
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SDSR: A Spectral Divide-and-Conquer Approach for Species Tree Reconstruction
This paper addresses the computational bottleneck in reconstructing species trees from thousands of species and multiple genes by introducing a scalab...
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.