PREDICTING SLOW STRUCTURAL TRANSITIONS IN MACROMOLECULAR SYSTEMS - CONFORMATIONAL FLOODING
PREDICTING SLOW STRUCTURAL TRANSITIONS IN MACROMOLECULAR SYSTEMS - CONFORMATIONAL FLOODING
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DOI：
10.1103/physreve.52.2893
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发表时间：
1995-09-01
影响因子：
2.4
通讯作者：
GRUBMULLER, H
中科院分区：
文献类型：
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作者：
GRUBMULLER, H
我们提出了一种在原子水平上预测不规则或无序大分子系统（如蛋白质或玻璃）中复杂结构（构象）转变的方法。我们的方法针对罕见的事件，目前无法预测与传统的分子动力学（MD）模拟，因为这些目前仅限于时间尺度短于几纳秒。给定系统的初始构象，我们的方法确定一个或多个产品状态，这可能是从初始状态分离的自由能障碍，是大规模的热能。它还提供了一个近似的反应路径，可用于确定势垒高度或反应速率与常用技术。该方法采用了一种人工电位，使初始构象不稳定，从而降低了结构转变的自由能垒。结果，转变被加速并且可以在MD模拟中观察到。给出了加速因子的分析估计。该方法适用于两个测试系统，氩微团簇和简化的蛋白质模型。通过这些研究，我们证明我们的方法能够将平均跃迁时间从0.5 μ s（氩团簇）和1.4 ns（蛋白质模型）缩短到几微微秒。这些结果表明，我们的方法是特别适合于研究生化相关的蛋白质在微秒的时间尺度上的构象运动。
We present a method to predict complex structural (conformational) transitions in irregular or disordered macromolecular systems, such as proteins or glasses, at the atomic level. Our method aims at rare events, which currently cannot be predicted with traditional molecular dynamics (MD) simulations, since these currently are limited to time scales shorter than a few nanoseconds. Given an initial conformation of the system, our method identifies one or more product states, which may be separated from the initial state by free energy barriers that are large on the scale of thermal energy. It also provides an approximate reaction path, which can be used to determine barrier heights or reaction rates with the usual techniques. The method employs an artificial potential that destabilizes the initial conformation and, thereby, lowers free energy barriers of structural transitions. As a result, transitions are accelerated and may be observed in MD simulations. An analytical estimate for the acceleration factor is given. The method is applied to two test systems, an argon microcluster and a simplified protein model. By these studies we demonstrated that our method is capable of shortening mean transition times from 0.5 mu s (argon cluster) and 1.4 ns (protein model) to a few picoseconds. These results suggest that our method is particularly well suited to study biochemically relevant conformational motions in proteins at a microsecond time scale.