Lehrstuhl für Theoretische Chemie, Ruhr-Universität Bochum, 44780 Bochum, Germany.
J Phys Chem Lett. 2020 Nov 5;11(21):9298-9303. doi: 10.1021/acs.jpclett.0c02902. Epub 2020 Oct 21.
The discovery of RNA enzymes, ribozymes, provided strong support to the RNA world hypothesis suggesting that early life evolved from RNAs able to both store genetic information and catalyze biochemical reactions. Moreover, evidence is accumulating that primitive life might have emerged in deep-sea environments and, thus, at high hydrostatic pressures. If true, ribozymes should be able to function under those pressures. In this work, we ask if and possibly how ribozymes could function at high pressures. To this end, we specifically focus on the chemical reaction steps of the self-cleavage catalysis of hairpin ribozyme by employing extensive QM/MM metadynamics simulations. We find that the reaction scenario at high pressures is vastly different than that at ambient conditions, yet the rate-limiting reaction barrier and, thus, the reaction rate are only marginally affected. Therefore, the results indeed suggest that ribozymes would function at high pressures but by following a vastly different reaction scenario.
RNA 酶（核酶）的发现为 RNA 世界假说提供了有力支持，该假说表明，早期生命是从既能储存遗传信息又能催化生化反应的 RNA 进化而来的。此外，越来越多的证据表明，原始生命可能是在深海环境中出现的，因此处于高压环境下。如果这是真的，核酶应该能够在这些压力下发挥作用。在这项工作中，我们探讨了核酶在高压下是否以及可能如何发挥作用。为此，我们特别关注发夹状核酶自身切割催化的化学反应步骤，采用了广泛的 QM/MM 元动力学模拟。我们发现，高压下的反应情景与环境条件下的反应情景大不相同，但限速反应势垒，因此，反应速率仅受到轻微影响。因此，这些结果确实表明核酶可以在高压下发挥作用，但遵循的是一个完全不同的反应情景。
