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

我们展示了一个部分自动化的计算模型，该模型将磷酸糖分子的五种简单反应机制转化为戊糖磷酸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起来，使用SMILES分子表示作为输入到eQuilibrator 3.0应用程序编程接口。输出数据是分子自由能的群体贡献估计，也是自动化的，可以任意大。只有我们将SMILES表示从图形化学语言MOD的输出转移到均衡器是手动完成的。我们分析了化学反应网络的拓扑结构，并证明了相同变换的所有可能路径都是由对称规则构建的有限循环基础构建的。我们使用该网络上的热化学数据来研究化学功的转导，并定义任何途径的进化成本函数。结果由PI在两次受邀演讲中报告：“进化中的组合学：从基于规则的系统到选择性热力学”，在芝加哥的美国物理学会三月会议上（https://meetings.aps.org/Meeting/MAR22/Session/K04.1），以及在保加利亚索非亚的“基于规则的系统的组合化学及其相关信息理论”（http://physicsoflivingsystems.org/events/workshop-life-in-the-universe/），部分由美国国家科学基金会赞助。

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.