多尺度研究蛋白质和核酸分子机器大尺度构象运动及催化作用机理
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- 英文论文题名：Multiscale study for large-scale conformational motions of protein and RNA molecular machines and their catalytic mechanisms
- 论文作者：廖结楼 ; 黄文婷 ; 王子 ; 黄云 ; 黄炎
- 英文论文作者：W.Huang ; Z.Wang ; Y.Huang ; Jie-Lou Liao ; Department of Chemical Physics ; University of Science and Technology
- 年：2016
- 作者机构：中国科学技术大学化学物理系;
- 论文关键词：多尺度方法 ; 蛋白质 ; 核酸 ; 构象变化 ; 催化机理
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第十九分会：化学中的量子与经典动力学
- 语种：中文
- 分类号：O641.3;O643.31
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第十九分会 ; 化学中的量子与经典动力学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：232k
- 原文格式：D
- 会议级别：全国
摘要
蛋白质和核酸分子通过结合或解离配体来调节其大尺度构象运动,并利用这些构象变化来实现其生物功能包括催化细胞中重要的生化反应。ATP盒式蛋白酶(ATP-binding cassette,ABC)和剪接体(spliceosome)是两个典型的例子。作为物质进出细胞的检查点(checkpoint),ABC结合ATP并催化其水解,驱动大尺度构象变化(控制进出细胞"门"的开与关),实现物质输出或输入细胞。剪接体是非常复杂的RNA-蛋白质分子机器,在分子生物学"中心法则"中起着非常重要的作用。剪接体在催化剪接pre-mR NA循环过程中,有序地结合或离解不同的sn RNA和蛋白质,通过它们的构象运动实现其催化剪接功能。由于对这些生物分子大尺度构象态跃迁研究存在长时间尺度问题,全原子分子动力学模拟方法无能为力;再加上催化循环周期中涉及化学键的断裂或生成,需要用量子化学方法来处理,解决这些问题远远超出当今计算机的处理能力。为克服这些困难,我们发展和应用了多尺度的量子力学/分子力学/粗粒化(QM/MM/CG)建模方法,对这些生物大分子体系(尤其是ABC输出酶)的构象变化和催化作用进行系统的研究[1-3],为理解其构象态跃迁的分子动力学(dynamics)和化学反应动力学(kinetics)机制架起桥梁,并为在原子尺度上详细阐述蛋白质构象变化如何影响其催化酶的功能提供帮助。
Protein and RNA molecular machines often perform large-scale conformational motions through ligand binding or dissociation to carry out biological functions including catalyzing important chemical reactions in cell. Two typical examples are ATP-binding cassette proteins(ABC) and spliceosome. As a transmembrane checkpoint, an ABC protein executes large-amplitude conformational changes by binding and hydrolyzing ATP to transport specific substrates across the membrane. Spliceosome, a complex RNA-protein machine playing an important role in the central dogma of molecular biology, assembles various sn RNA and proteins, accompanying large-scale conformational changes to catalyze the pre-mR NA splicing. Owing to the notorious long time-scale problem, all-atom molecular dynamics(MD) is not able to describe these macromolecular motions particularly involving bond breaking and formation. Our studies aim to overcome this problem by applying a QM/MM/CG strategy. Some promising results have been obtained and published particularly for ABC proteins in our study.
Protein and RNA molecular machines often perform large-scale conformational motions through ligand binding or dissociation to carry out biological functions including catalyzing important chemical reactions in cell. Two typical examples are ATP-binding cassette proteins(ABC) and spliceosome. As a transmembrane checkpoint, an ABC protein executes large-amplitude conformational changes by binding and hydrolyzing ATP to transport specific substrates across the membrane. Spliceosome, a complex RNA-protein machine playing an important role in the central dogma of molecular biology, assembles various sn RNA and proteins, accompanying large-scale conformational changes to catalyze the pre-mR NA splicing. Owing to the notorious long time-scale problem, all-atom molecular dynamics(MD) is not able to describe these macromolecular motions particularly involving bond breaking and formation. Our studies aim to overcome this problem by applying a QM/MM/CG strategy. Some promising results have been obtained and published particularly for ABC proteins in our study.
引文
[1]Z.Wang and Jie-Lou Liao*.Probing structural determinants of ATP-binding cassette exporter conformational transition using coarse-grained molecular dynamics.J.Phys.Chem.B.2015,119:1295-1301.
[2]W.Wang,W.Huang,and Jie-Lou Liao*.QM/MM investigation of ATP hydrolysis in aqueous solution.J.Phys.Chem.B 2015,119:3720-3726.
[3]W.Huang and Jie-Lou Liao*.Catalytic mechanism of the maltose transporter hydrolyzing ATP.Biochemistry2016,55:224-231.
[2]W.Wang,W.Huang,and Jie-Lou Liao*.QM/MM investigation of ATP hydrolysis in aqueous solution.J.Phys.Chem.B 2015,119:3720-3726.
[3]W.Huang and Jie-Lou Liao*.Catalytic mechanism of the maltose transporter hydrolyzing ATP.Biochemistry2016,55:224-231.