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化学进展 2012, Vol. 24 Issue (05): 784-789 前一篇   后一篇

所属专题： 计算化学

• 综述与评论 •

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

林英武1,2*   

  1. 1. 南华大学化学化工学院 衡阳 421001;
    2. 南京大学配位化学国家重点实验室 南京 210093
  • 收稿日期:2011-09-01 修回日期:2011-12-01 出版日期:2012-05-24 发布日期:2012-04-10
  • 基金资助:
    国家自然科学基金青年基金项目(No.21101091)、南京大学配位化学国家重点实验室开放基金项目、湖南省自然科学基金青年基金项目(No.11JJ4017)和湖南省教育厅青年基金项目(No.11B105)资助
下载PDF ( 949 ) 引用
导出 被引次数 ( 6 | 1 )

Computer-Aided Rational Protein Design: From Myoglobin to Nitric Oxide Reductases

Lin Yingwu1,2*   

  1. 1. School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China;
    2. State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, China
  • Received:2011-09-01 Revised:2011-12-01 Online:2012-05-24 Published:2012-04-10
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。
关键词： 肌红蛋白, 一氧化氮还原酶, 金属结合位点, 分子设计, 分子模拟
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.

Contents
1 Introduction
2 Myoglobin: an ideal scaffold for protein molecular design
3 Nitric oxide reductase: both a chance and a challenge for protein molecular design
4 Exploring unknown areas: ongoing of protein molecular design
5 Conclusion and outlook

Key words: myoglobin, nitric oxide reductase, metal-binding site, molecular design, molecular simulation

中图分类号: 

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