计算机辅助蛋白质分子理性设计：从肌红蛋白到一氧化氮还原酶

摘要

Computer-aided rational protein design was demonstrated to be effective in addressing important issues in chemistry and biology.With computer simulation,a structural and functional nitric oxide reductase（NOR） was successfully designed using myoglobin（Mb） as a protein model,which was accomplished at the time with no three dimensional structure available for NOR itself.More importantly,the designed NOR protein model,FeBMb,was confirmed by an X-ray structure of native NOR one year later.The progress and rationalities of design of FeBMb,I107E FeBMb,as well as FeBMb（-His）,were reviewed herein.The use of molecular simulation to obtain atomic structural information on Mb in a non-native state with bis-Histidine coordination was also highlighted,as the information was otherwise difficult to obtain experimentally.The general application of computer-aided rational protein design will provide deep insight into biological systems.%计算机辅助蛋白质分子理性设计在解决化学及生物学重要问题中被证实十分有效。在NOR本身三维结构未知的情况下通过计算机分子模拟,使用肌红蛋白（Mb）作为蛋白质分子模型,设计了结构功能型一氧化氮还原酶（NOR）,所设计的NOR蛋白质模型——FeBMb一年后被天然NOR的晶体结构所证实。本文综述了设计FeBMb,I107E FeBMb以及FeBMb（-His）的研究过程及其设计合理性,评述了通过使用计算机分子模拟,获得Mb处于双组氨酸配位的非天然状态的原子层次结构信息,而这些信息很难通过实验方法来获得。计算机辅助蛋白质分子理性设计的广泛应用将会为生物体系提供更深刻的内涵。