Drt3b 介导蛋白模板化周期-2 DNA 合成的再生自由能寄存器
A regenerating free-energy register for protein-templated period-2 DNA synthesis by Drt3b
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中文总结 AI 辅助
本研究针对 Drt3b 合成聚(AC) DNA 的机制，提出其为再生蛋白-底物自由能寄存器的理论框架，可联合预测核苷酸选择等多类实验结果，无需额外量子计算或外场耦合。
中文摘要 AI 辅助
Deng 等人发现，Drt3b 可在无核酸模板的情况下合成蛋白引发的聚(AC) DNA。相关结构揭示了有限的蛋白结构及产物相关的相互作用，但未阐明将受限口袋转化为长周期-2序列的可再生动力学规则。我们提出，Drt3b 是一种再生蛋白-底物自由能寄存器。该框架规定了采样量子力学/分子力学（QM/MM）平均力势，以及域内预注册的一阶电子描述符图，用于边缘特异性活化能垒；物理曲率仅通过训练冻结的泰勒余项界引入，该界会扩大不确定性但不修正保留的均值。从这些能垒推导的条件风险，在未解析的构象、水合、质子化及金属配位轨迹上取平均，得到半马尔可夫事件核。因此，竞争风险的逐点比值由相同的能垒差和预注册的 prefactor 规则确定，这些规则决定了退出时机，因此核苷酸选择和停留统计是协同生成的，而非单独拟合。一个机制门将平稳或缓慢驱动的实验（通过联合序列-时间循环行列式分析）与真正非平稳的实验（通过完整年龄结构倾斜传播子分析）区分开。决定性测试采用锁定参数化：无需针对特定条件重新拟合，该参数化必须联合预测核苷酸选择、等待时间规律、产物长度尾部，以及扰动响应的秩、子式、零空间和 rescue 结构。2026 年一项独立的 DRT3 研究在序列和结构比对冻结后，提供了严格的跨构建体传输测试。该方案既不需要相干量子计算，也不需要与外场耦合。
英文摘要
Deng et al. discovered that Drt3b synthesizes protein-primed poly(AC) DNA without a nucleic-acid template. The structures reveal a finite protein architecture and product-associated contacts, but not the renewable dynamical rule that converts a bounded pocket into a long period-2 sequence. We propose that Drt3b is a regenerating protein-substrate free-energy register. The framework specifies a sampled quantum mechanics/molecular mechanics (QM/MM) potential of mean force and a preregistered, within-domain first-order electronic-descriptor map for edge-specific activation barriers; physical curvature is admitted only through a training-frozen Taylor-remainder bound that widens uncertainty but never corrects a held-out mean. Conditional hazards derived from those barriers are averaged over unresolved conformational, hydration, protonation, and metal-coordination trajectories to yield a semi-Markov event kernel. Pointwise ratios of competing hazards are therefore fixed by the same barrier differences and preregistered prefactor rules that govern exit timing, so nucleotide choice and dwell statistics are co-generated rather than separately fitted. A regime gate separates stationary or slowly driven experiments, analyzed by a joint sequence-time cycle determinant, from genuinely nonstationary protocols, analyzed by the full age-structured tilted propagator. The decisive test is one locked parameterization: without condition-specific refitting, it must jointly predict nucleotide choice, waiting-time laws, product-length tails, and the rank, minors, null spaces, and rescue structure of perturbation responses. An independent 2026 DRT3 study supplies a stringent cross-construct transport test after sequence and structural alignment are frozen. The proposal requires neither coherent quantum computation nor coupling to an external field.
发表机构
- Adventin Inc.（Adventin公司）
机构由 AI 辅助整理，请以论文原文为准。
