对于一个毫秒文件的ab initio蛋白质折叠的分子模拟NTL9(1-39)
Vincent A Voelz1, Gregory R Bowman, Kyle Beauchamp
1Department of Chemistry, Stanford University, Stanford, California 94305, USA.
Journal of the American Chemical Society
|January 15, 2010
概括
研究人员使用分子动力学模拟了蛋白质折叠,实现了NTL9的毫秒时间尺度 ((1-39). 蛋白质折叠模拟的这一突破为beta的速度限制步骤提供了洞察力.
科学领域:
- 计算生物学是一种计算生物学.
- 生物物理学的生物物理.
- 分子动力学模拟的模拟.
背景情况:
- 以前的全原子分子动力学模拟实现了纳秒到微秒范围内的蛋白质折叠时间.
- 蛋白质NTL9(1-39) 的实验确定折叠时间约为1.5毫秒.
研究的目的:
- 为了模拟NTL9的折叠 ((1-39) 到超出微秒的时间尺度.
- 使用计算方法研究NTL9的折叠路径和动力学.
主要方法:
- 在GPU处理器上的隐性溶剂中进行分布式分子动力学模拟.
- 在各种温度和起始状态下生成轨迹合集.
- 从模拟数据构建马尔科夫状态模型 (MSM).
主要成果:
- 在低于力场点的温度下观察到生产性折叠事件.
- 从模拟中预测的折叠率与实验值 (~640/s) 非常相匹配.
- MSM表明了两种状态的折叠和异质路径,其中β(12) 发针形成可能会限制速度.
结论:
- 模拟成功地将蛋白质折叠动态扩展到毫秒时间尺度.
- 识别了beta(12) 发针形成作为NTL9(1-39) 折叠中的潜在速度限制步骤.
- 拟议的适应性重新采样模拟作为一种方法,以在更长的时间范围内实现折叠景观的融合描述.
相关概念视频
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Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
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Molecular Chaperones and Protein Folding
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Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence.
The primary structure of a protein is its amino acid sequence.


