On the simulation of protein folding by short time scale molecular dynamics and distributed computing
On the simulation of protein folding by short time scale molecular dynamics and distributed computing
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DOI：
10.1073/pnas.182542699
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发表时间：
2002-10-29
影响因子：
11.1
通讯作者：
Fersht, AR
中科院分区：
文献类型：
--
作者：
Fersht, AR
有人建议通过使用大量仅数十纳秒的短模拟（分布式计算）来克服当前蛋白质折叠的时间尺度与分子动力学模拟之间的不兼容性。根据一阶动力学过程的原理，足够多的短期模拟实际上将包括少量已经完成的长时间尺度事件。但蛋白质折叠并不是一个基本的动力学步骤：折叠具有一系列早期构象步骤，这些步骤导致动力学开始时的滞后阶段。这些滞后阶段的存在可能会使短模拟偏向于选择具有更少或更快滞后步骤的次要路径，从而错过主要折叠路径。由于在分子动力学模拟中检测跃迁很困难，尝试通过使用松散耦合的并行模拟来搜索一阶跃迁来规避滞后也是有问题的。然而，一旦模拟的时间尺度经过滞后阶段进入单个指数区域，使用并行独立模拟的过程是完全有效且相当可行的。
There are proposals to overcome the current incompatibilities between the time scales of protein folding and molecular dynamics simulation by using a large number of short simulations of only tens of nanoseconds (distributed computing). According to the principles of first-order kinetic processes, a sufficiently large number of short simulations will include, de facto, a small number of long time scale events that have proceeded to completion. But protein folding is not an elementary kinetic step: folding has a series of early conformational steps that lead to lag phases at the beginning of the kinetics. The presence of these lag phases can bias short simulations toward selecting minor pathways that have fewer or faster lag steps and so miss the major folding pathways. Attempts to circumvent the lags by using loosely coupled parallel simulations that search for first-order transitions are also problematic because of the difficulty of detecting transitions in molecular dynamics simulations. Nevertheless, the procedure of using parallel independent simulations is perfectly valid and quite feasible once the time scale of simulation proceeds past the lag phases into a single exponential region.