在随机多步动力学证明读中实现可靠的配体区分：首次通过时间与产物计数策略
Reliable ligand discrimination in stochastic multistep kinetic proofreading: First passage time vs. product counting strategies
AI总结：
研究通过重构动力学证明读理论，探讨首次通过时间与产物计数策略在不同生物背景下对信号特异性的影响，揭示长证明读步骤在高噪声环境下仍具有效性。
摘要：
细胞信号转导对于生物过程如免疫反应和稳态至关重要，依赖于信号转导的特异性和保真度以在生物噪声中准确响应刺激。动力学证明读（KPR）是通过时间延迟步骤增强信号特异性的关键机制，但其有效性因内在噪声可能降低信号保真度。本文通过将多个中间状态整合为单一状态并定义整体“处理”时间，重构了KPR理论。这种简化使我们能够用单一等待时间参数描述KPR，从而更直接评估和比较不同生物背景下KPR性能。研究发现，长证明读步骤的保真度损失依赖于信息提取的具体策略，并表明在首次通过时间（FPT）区分策略中，长证明读步骤可指数级提高KPR准确性，但以速度为代价。因此，KPR在高噪声环境下仍是一种有效的区分机制。然而，在基于产物浓度的区分策略中，长证明读步骤不一定提升性能。通过引入产物浓度的激活阈值，可以将产物策略分解为一系列FPT策略，以更好地解析KPR介导的产物区分的细微差别。研究结果强调了在细胞中信息提取和处理背景下理解KPR的重要性。
英文摘要：
Cellular signaling, crucial for biological processes like immune response and homeostasis, relies on specificity and fidelity in signal transduction to accurately respond to stimuli amidst biological noise. Kinetic proofreading (KPR) is a key mechanism enhancing signaling specificity through time-delayed steps, although its effectiveness is debated due to intrinsic noise potentially reducing signal fidelity. In this study, we reformulate the theory of kinetic proofreading (KPR) by convolving multiple intermediate states into a single state and then define an overall "processing" time required to traverse these states. This simplification allows us to succinctly describe kinetic proofreading in terms of a single waiting time parameter, facilitating a more direct evaluation and comparison of KPR performance across different biological contexts such as DNA replication and T cell receptor (TCR) signaling. We find that loss of fidelity for longer proofreading steps relies on the specific strategy of information extraction and show that in the first-passage time (FPT) discrimination strategy, longer proofreading steps can exponentially improve the accuracy of KPR at the cost of speed. Thus, KPR can still be an effective discrimination mechanism in the high noise regime. However, in a product concentration-based discrimination strategy, longer proofreading steps do not necessarily lead to an increase in performance. However, by introducing activation thresholds on product concentrations, can we decompose the product-based strategy into a series of FPT based strategies to better resolve the subtleties of KPR-mediated product discrimination. Our findings underscore the importance of understanding KPR in the context of how information is extracted and processed in the cell.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
