Using chemical thermodynamics on networks to understand the universality of biological sugar-phosphate metabolism

我们演示了一个部分自动化的计算模型，该模型将糖-磷酸分子的五个简单反应机制转换为磷酸戊糖途径转化问题的所有可能化学解决方案的列表。我们将自动生成的化合物列表与热化学数据的提取结合在一起，使用SSILES分子表示作为平衡器3.0应用程序编程接口的输入。输出数据是分子自由能的基团贡献估计，也是自动化的，可以任意大小。只有我们的微笑表示从图形化学语言MOD的输出到平衡器的转换是手工完成的。我们分析了化学反应网络的拓扑结构，并证明了相同转换的所有可能的路径都是由可以由对称规则构造的有限循环基构造的。我们使用这个网络上的热化学数据来研究化学功的传递，并为任何途径定义一个进化成本函数。国际和平研究所在两次特邀演讲中报告了结果：美国物理学会3月在芝加哥举行的会议上发表的《进化中的组合学：从基于规则的系统到选择性的热力学》((https://meetings.aps.org/Meeting/MAR22/Session/K04.1)，以及由美国国家科学基金会部分赞助的在保加利亚索非亚举行的《组合化学与基于规则的系统及其相关信息理论》((http://physicsoflivingsystems.org/events/workshop-life-in-the-universe/)。

We demonstrated a partly-automated computational model that converts five simple reaction mechanisms for sugar-phosphate molecules into a list of all possible chemical solutions to the conversion problem of the Pentose Phosphate Pathway. We coupled the automatically-generated list of compounds to extraction of thermochemical data using the SMILES molecules representation as input to the eQuilibrator 3.0 Application Programming Interface. The output data are group-contribution estimates for molecular free energy, and are also automated and can be arbitrarily large. Only our transfer of SMILES representation from the output of the graph-chemistry language MOD to eQuilibrator has been done manually.We analyzed the topology of the chemical reaction network and proved that all possible pathways for the same transformation are constructed from a finite basis of circulations that can be constructed from symmetry rules. We used the thermochemical data on this network to study the transduction of chemical work, and to define an evolutionary cost function for any pathway. Results were reported by the PI in two invited presentations: "Combinatorics in evolution: From rule-based systems to the thermodynamics of selectivities" at the American Physical Society March meeting in Chicago (https://meetings.aps.org/Meeting/MAR22/Session/K04.1 ), and "Combinatorial Chemistry with Rule-Based Systems and its Associated Information Theory" in Sofia Bulgaria (http://physicsoflivingsystems.org/events/workshop-life-in-the-universe/ ), partly sponsored by the U.S. National Science Foundation.