MTA-DE Momentum Laboratory of Protein Dynamics, Department of Biochemistry and Molecular Biology, University of Debrecen, Hungary.
Department of Engineering, University of Cambridge, United Kingdom.
Curr Opin Chem Biol. 2014 Aug;21:34-41. doi: 10.1016/j.cbpa.2014.03.011. Epub 2014 Apr 24.
Computational design is becoming an integral component in developing novel enzymatic activities. Catalytic efficiencies of man-made enzymes however are far behind their natural counterparts. The discrepancy between laboratory and naturally evolved enzymes suggests that a major catalytic factor is still missing in the computational process. Reorganization energy, which is the origin of catalytic power of natural enzymes, has not been exploited yet for design. As exemplified in case of KE07 Kemp eliminase, this quantity is optimized by directed evolution. Mutations beneficial for evolution, but without direct impact on catalysis can be identified based on contributions to reorganization energy. We propose to incorporate the reorganization energy in scaffold selection to provide highly evolvable initial designs.
计算设计正在成为开发新型酶活性的一个组成部分。然而，人工酶的催化效率远远落后于天然酶。实验室酶和天然进化酶之间的差异表明，计算过程中仍然缺少一个主要的催化因素。重组能是天然酶催化能力的起源，但尚未在设计中得到利用。以 KE07 Kemp 消除酶为例，该能量通过定向进化得到优化。可以根据对重组能的贡献来识别对进化有益但对催化没有直接影响的突变。我们建议将重组能纳入支架选择中，以提供高度可进化的初始设计。
