Kazlauskas R J
Department of Chemistry, McGill University, Montréal, H3A 2K6, Canada.
Curr Opin Chem Biol. 2000 Feb;4(1):81-8. doi: 10.1016/s1367-5931(99)00056-3.
Rapid advances in structural biology have revealed the three-dimensional structures of many biocatalysts. Molecular modeling is the tool that links these structures with experimental observations. As a qualitative tool, current modeling methods are extremely useful. They can explain, on a molecular level, unusual features of reactions. They can predict how to increase the selectivity either by substrate modification or by site-directed mutagenesis. Quantitative predictions, for example the degree of enantioselectivity, are still not reliable, however. Modeling is limited also by the availability of three-dimensional structures. Most current modeling involves hydrolases, especially proteases and lipases, but structures for other types of enzymes are starting to appear.
结构生物学的迅速发展揭示了许多生物催化剂的三维结构。分子建模是将这些结构与实验观察联系起来的工具。作为一种定性工具，当前的建模方法非常有用。它们可以在分子水平上解释反应的异常特征。它们可以预测如何通过底物修饰或定点诱变来提高选择性。然而，定量预测，例如对映体选择性的程度，仍然不可靠。建模还受到三维结构可用性的限制。目前大多数建模涉及水解酶，尤其是蛋白酶和脂肪酶，但其他类型酶的结构也开始出现。
