PNAS Plus Significance Statements
PNAS Plus Significance Statements
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DOI：
10.1073/pnas.ss1155
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Charles;Doubleday;Jiyong Park;Ashay Patel;W. Russell;D. Russell;K. Houk;J. McCoy;Melanie J. Mills;K. Walton;R. Thomas;Cotton;Paul Gregorevic;C. Harrison
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文献类型：
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作者：
Charles;Doubleday;Jiyong Park;Ashay Patel;W. Russell;D. Russell;K. Houk;J. McCoy;Melanie J. Mills;K. Walton;R. Thomas;Cotton;Paul Gregorevic;C. Harrison
用精确的量子力学方法研究酶反应的时间分辨机理是计算化学的圣杯，我们现在发展了一种有效的方法--环境扰动过渡态采样，用于研究酶的单分子轨迹和计算活化势垒。2011年，Liu团队发表了Spinosyn A生物合成途径中第一个单功能Diels-Alderase SpnF的证据。我们后来发现，该反应通过单一的双峰过渡态分叉为[4+2]和[6+4]加合物。我们现在详细阐明反应的机理，并展示SpnF酶如何动态控制产物的形成。我们的方法将在控制选择性的酶的设计中得到很好的应用，特别是对于涉及双峰过渡态的反应。(见pp.E848-E855。)
The investigation of time-resolved mechanisms of enzymatic reaction with accurate quantum-mechanics method is a holy grail of computational chemistry, and we now develop an efficient method, environmentperturbed transition-state sampling, to study singlemolecule trajectories in enzymes and calculate activation barriers. In 2011, the Liu group published evidence for the first monofunctional Diels–Alderase, SpnF, in the biosynthetic pathway of Spinosyn A. We discovered later that the reaction bifurcates to the [4+2] and [6+4] adduct through a single ambimodal transition state. We now elucidate in detail the mechanism of the reaction and show how the SpnF enzyme dynamically controls product formation. Our method will find great application in the design of enzymes to control selectivity, particularly for reactions involving ambimodal transition states. (See pp. E848–E855.)