科學家實現複雜天然產物合成的計算機設計
作者：
小柯機器人發布時間：2020/10/15 15:35:20
韓國蔚山科技大學Bartosz A. Grzybowski等研究人員合作實現複雜天然產物合成的計算機設計。這一研究成果於2020年10月13日在線發表在國際學術期刊《自然》上。
研究人員表示，教會計算機來計劃多步有機合成已成為50多年來的挑戰。自從早期的開創性貢獻以來，包括諸如LHASA之類的程序（由操作員在每個步驟做出反應選擇），該領域取得了長足的進步，現在有多個軟體平臺可以完全自主地進行規劃。不過，這些程序一次只能「思考」一次，並且到目前為止僅限於相對簡單的目標，可以說，它們的合成可以由人類化學家在幾分鐘內無需計算機的幫助下進行設計。迄今為止，還沒有一種算法能夠設計出通向複雜天然產物的合理路線，為此，必須進行複雜的多步計劃，並且不能依靠緊密相關的文獻先例。
研究人員證明了這樣的路線選擇是可行的，假如這一機器對有機化學和基於數據的人工智慧程序的了解與因果關係得以增強，從而使其能夠在多個合成步驟上制定策略。通過這些改進，對合成專家進行的類似圖靈測試的結果表明，計算機設計的路線與人類設計的路線在很大程度上沒有區別。在實驗室中成功驗證了三種計算機設計的天然產物合成物。綜上所述，這些結果表明，專家級的自動綜合計劃最終將變得可行，但這需要對反應知識基礎的不斷改進和進一步的代碼優化。
附：英文原文
Title: Computational planning of the synthesis of complex natural products
Author: Barbara Mikulak-Klucznik, Patrycja Gobiowska, Alison A. Bayly, Oskar Popik, Tomasz Klucznik, Sara Szymku, Ewa P. Gajewska, Piotr Dittwald, Olga Staszewska-Krajewska, Wiktor Beker, Tomasz Badowski, Karl A. Scheidt, Karol Molga, Jacek Mynarski, Milan Mrksich, Bartosz A. Grzybowski
Issue&Volume: 2020-10-13
Abstract: Teaching computers to plan multistep organic syntheses has been a challenge for over 50 years1–7. Since early pioneering contributions, including programs such as LHASA1,7 (with reaction choices at each step made by human operator), the field has progressed greatly and there are now multiple software platforms6,8–13 capable of completely autonomous planning. Still, these programs 『think』 only one step at a time and have so far been limited to relatively simple targets whose syntheses could, arguably, be designed by human chemists within minutes and without computer’s help. To date, no algorithm has been able to design plausible routes to complex natural products for which significantly more far-sighted, multi-step planning is necessary14,15 and for which one cannot rely on closely related literature precedents. Here we demonstrate that such route choices are possible, provided that the machine’s knowledge of organic chemistry and data-based artificial intelligence routines are augmented with causal relationships16,17, allowing it to strategize over multiple synthetic steps. With these improvements, results of a Turing-like test administered to synthesis experts indicate that the routes designed by computer become largely indistinguishable from those designed by humans. Three computer-designed syntheses of natural products were successfully validated in the lab. Taken together, these results indicate that automated synthetic planning at an expert level is finally becoming feasible, pending continued improvements to the reaction-knowledge base and further code optimization.
DOI: 10.1038/s41586-020-2855-y
Source: https://www.nature.com/articles/s41586-020-2855-y