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微秒到秒原子折叠时间的计算估计

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科学领域:

  • 计算生物学
  • 生物物理
  • 分子动力学

背景情况:

  • 在室温下模拟原子蛋白折叠仅限于常规分子动力学 (MD) 的微秒.
  • 在GPU计算方面的进步为更长时间的模拟提供了潜力.

研究的目的:

  • 使用加权组合 (WE) 策略与GPU计算相结合,报告原子蛋白系统的折叠.
  • 为了能够对蛋白质折叠等罕见事件的速率常数进行统计学上公正的估计.

主要方法:

  • 使用加权组合 (WE) 策略与GPU加速的MD模拟.
  • 使用修剪和复制进行公正估计的轨迹段组合.
  • 使用WE概率流和历史增强的马尔科夫分析分析折叠时间.

主要成果:

  • 成功模拟了从微秒到毫秒的折叠时间的原子化,隐性溶解蛋白质.
  • 在不同的粘度下检查NTL9 (0.8-9微秒和0.2-2毫秒) 和蛋白G (3-200毫秒).
  • WE模拟提供了折叠时间,不确定性和组合属性,比传统的MD对蛋白质G的计算更少.

结论:

  • 使用GPU计算的WE策略可用于模拟较长时间的蛋白质折叠.
  • 这种方法允许统计学上不偏地估计运动量,包括折叠时间和不确定性.
  • 这些发现表明使用和校准力场和溶剂模型进行精确的动力估计是可行的.