Schaller Kay S, Kari Jeppe, Molina Gustavo A, Tidemand Kasper D, Borch Kim, Peters Günther H J, Westh Peter
Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads, DK-2800 Kgs. Lyngby, Denmark.
Department of Chemistry, Technical University of Denmark, Kemitorvet, DK-2800 Kgs. Lyngby, Denmark.
ACS Omega. 2021 Jan 6;6(2):1547-1555. doi: 10.1021/acsomega.0c05361. eCollection 2021 Jan 19.
While heterogeneous enzyme reactions play an essential role in both nature and green industries, computational predictions of their catalytic properties remain scarce. Recent experimental work demonstrated the applicability of the Sabatier principle for heterogeneous biocatalysis. This provides a simple relationship between binding strength and the catalytic rate and potentially opens a new way for inexpensive computational determination of kinetic parameters. However, broader implementation of this approach will require fast and reliable prediction of binding free energies of complex two-phase systems, and computational procedures for this are still elusive. Here, we propose a new framework for the assessment of the binding strengths of multidomain proteins, in general, and interfacial enzymes, in particular, based on an extended linear interaction energy (LIE) method. This two-domain LIE (2D-LIE) approach was successfully applied to predict binding and activation free energies of a diverse set of cellulases and resulted in robust models with high accuracy. Overall, our method provides a fast computational screening tool for cellulases that have not been experimentally characterized, and we posit that it may also be applicable to other heterogeneously acting biocatalysts.
虽然多相酶反应在自然界和绿色工业中都起着至关重要的作用，但其催化特性的计算预测仍然很少。最近的实验工作证明了萨巴蒂尔原理在多相生物催化中的适用性。这提供了结合强度与催化速率之间的简单关系，并有可能为动力学参数的廉价计算测定开辟一条新途径。然而，这种方法的更广泛应用将需要快速可靠地预测复杂两相系统的结合自由能，而为此的计算程序仍然难以捉摸。在这里，我们提出了一个新的框架，用于评估多结构域蛋白质，特别是界面酶的结合强度，该框架基于扩展的线性相互作用能（LIE）方法。这种双结构域LIE（2D-LIE）方法成功地应用于预测多种纤维素酶的结合和活化自由能，并产生了具有高精度的稳健模型。总体而言，我们的方法为尚未经过实验表征的纤维素酶提供了一种快速的计算筛选工具，并且我们认为它也可能适用于其他异相作用的生物催化剂。
