人工智能捕捉了在多面信号转换器,TAK1的化学架构中演变的伪智能
Nibedita Ray Chaudhuri1, Shubhra Ghosh Dastidar1
1Biological Sciences, Bose Institute, EN 80, Sector V, Bidhan Nagar, Kolkata - 700091, India.
Journal of chemical information and modeling
|June 26, 2025
概括
这项研究揭示了多功能激酶TAK1如何使用双切换机制来处理化学和机械信号,从而产生共享的催化结果. 它强调了TAK1的特点.
科学领域:
- 生物化学和结构生物学
- 计算生物学和生物信息学
- 分子信号传输的方法
背景情况:
- TAK1 (转化生长因子激活激酶1) 是一个关键的激酶,参与各种信号通路.
- 像TAK1这样的多功能蛋白质通过复杂的分子内相互作用来整合各种信号.
- 了解TAK1的动态适应性是解读其在细胞过程中的作用的关键.
研究的目的:
- 阐明TAK1对化学和机械激活触发器的反应中的双切换机制.
- 揭示多功能蛋白质使用的动态适应性和上下文依赖的策略.
- 探索新的计算方法来分析蛋白质机制.
主要方法:
- 对TAK1.1的计算建模和模拟.
- 开发一种新的AI/ML管道,包括基于差异接触的预选和基于VMD的3D可视化.
- 在蛋白质机制学研究中应用科尔莫戈罗夫-阿诺德网络 (KAN) 进行特征选择.
主要成果:
- TAK1采用不同的空间 (响应分歧 → 趋同) 和时间 (响应重定向) 策略来处理激活线索.
- 特定的残留物 (例如,R44-E70) 对于形成TAK1的全相互作用电路至关重要.
- 包括KAN在内的AI/ML方法有效地提取隐藏的交互指纹,并揭示了机械洞察力.
结论:
- TAK1的双开关机制允许高效且可适应的信号传输.
- 新的AI/ML方法可以显著推进复杂蛋白质动态的研究.
- 这些发现为设计针对多功能蛋白质的向疗法提供了结构性原则.
更多相关视频
12:24Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy
Published on: September 29, 2016
7.1K
14:02Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
Published on: April 9, 2018
8.6K
相关概念视频
Transduction
135
Among the three main modes of HGT—transformation, conjugation, and transduction—transduction is unique in that it is mediated by bacteriophages, or bacterial viruses.Transduction occurs in two ways. Generalized transduction occurs during the lytic cycle of a bacteriophage infection. In this process, bacteriophages infect bacterial cells, replicate within them, and ultimately cause cell lysis, releasing newly assembled virions. Occasionally, random fragments of the bacterial genome...
135
Amplifying Signals via Enzymatic Cascade
9.3K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
9.3K
Transducer Mechanism: Enzyme-Linked Receptors
2.8K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.8K
Assembly of Signaling Complexes
6.0K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
6.0K
Interactions Between Signaling Pathways
6.6K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.6K
Calmodulin-dependent Signaling
5.3K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.3K
