| 研究課題/領域番号 |
22K03792
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| 研究機関 | 東京工業大学 |
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研究代表者 |
スミス エリック 東京工業大学, 地球生命研究所, 特任教授 (50770468)
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| 研究分担者 |
Smith Harrison 東京工業大学, 地球生命研究所, 研究員 (50843934)
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| 研究期間 (年度) |
2022-04-01 – 2025-03-31
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| キーワード | Chemical networks / Rule-based systems / Chemical graph grammars / Systems chemistry / Thermochemical databases / Sugar metabolism / Evolution optimization / Natural selection cost |
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| 研究実績の概要 |
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.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
In January 2023, the architects of the MOD software platform for
graph-grammar computational chemistry, Jakob Andersen (U. Southern
Denmark) and Christoph Flamm (U. Vienna), were hosted for 10 days at
the Earth-Life Science Institute at Tokyo Institute of Technology to
work with PI Smith and Co-I Smith to design the fully-automated computational pipeline from graphical rules to thermochemical landscapes and kinetic models. The essential modules to interface the software MOD and eQuilibrator 3.0, and other thermochemical network packages including CHNOSZ, were specified as a process map. The four researchers now maintain monthly conference calls to implement these interface components in Python scripts that connect to the MOD, eQuilibrator 3.0, and CHNOSZ Application Programming Interfaces. All required software runs native on the researchers' personal computers.
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| 今後の研究の推進方策 |
Three publications are planned for submission in 2023. The first summarizes presents a theory of the dissipation and work relations on chemical networks derived from the topological properties of the networks, based on our automatically-generated sugar-phosphate chemistries. These relations are the input to understanding biological optimization of observed pathways under evolution. The second paper will analyze the universality of biological sugar-phosphate chemistry using the dissipation and work results currently derived. The third paper will be for computational chemists, presenting the high-throughput pipeline that combines graph-grammar and thermochemical database methods in high-throughput fashion.
As part of a collaboration with a PhD student of PI Smith in the US, we have also modeled the set of all autocatalytic cores in the sugar-phosphate system. In 2023 we will relate the subnetworks capable of autocatalytic self-amplification to our existing topological analysis of the basis of all cycles in that network.
Work has also begun with current colleagues in France and Austria to develop rules sets describing their experimental results on mechanisms of prebiotic carbon fixation, which was promised as the third, high-risk part of our project. We plan in 2023 to assemble those rules into networks like our existing network for sugar phosphate chemistry, and to compare energy flow paths in prebiotic chemistry and extant biochemistry. Those works will be compared with new results obtained within ELSI and JAMSTEC on carbon fixation through electrochemical mechanisms.
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| 次年度使用額が生じた理由 |
Publications charges were not needed in year 2022 because the time to prepare and submit articles was longer than the fiscal year. Several publications are being prepared in parallel, and will be submitted in year 2023. We expect the extra publication charges to be accumulated in this year.
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| 備考 |
Collaborations with the University of Southern Denmark and the University of Vienna do not involve any shared funding. We use KAKENHI operating funds to host collaborators for software construction.
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