Avoiding False Positive Conclusions in Molecular Simulation: The Importance of Replicas
Avoiding False Positive Conclusions in Molecular Simulation: The Importance of Replicas
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DOI：
10.1021/acs.jctc.8b00391
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发表时间：
2018-12-01
影响因子：
5.5
通讯作者：
Deane, Charlotte M.
中科院分区：
文献类型：
--
作者：
Knapp, Bernhard;Ospina, Luis;Deane, Charlotte M.
分子模拟是一种用于研究蛋白质和其他分子动力学的计算技术。这些模拟的自由能景观通常是崎岖不平的，初始速度、浮点精度或底层硬件的微小差异可能会导致相同的模拟（副本）在景观中采取不同的路径。在本研究中，我们基于 310 000 ns 的模拟时间研究了这些影响的程度。我们对一个小的 10 个氨基酸系统进行了 100 个相同的参数化复制，每个 3000 ns，并对 827 个残基 T 细胞受体/MHC 系统进行了 100 个相同的参数化复制，每个 100 ns。比较这些副本集中随机选择的子组，我们估计了给定模拟时间给定数量的副本可以实现的再现性和可靠性。这些结果表明，从单个模拟中得出的结论通常不可重复，并且从多个较短的复制品中得出的结论比从单个较长的模拟中得出的结论更可靠。所需副本的实际数量始终取决于所提出的问题和所寻求的可靠性级别。根据我们的数据，一个好的经验法则似乎是执行至少 5 到 10 个副本。
Molecular simulations are a computational technique used to investigate the dynamics of proteins and other molecules. The free energy landscape of these simulations is often rugged, and minor differences in the initial velocities, floating-point precision, or underlying hardware can cause identical simulations (replicas) to take different paths in the landscape. In this study we investigated the magnitude of these effects based on 310 000 ns of simulation time. We performed 100 identically parametrized replicas of 3000 ns each for a small 10 amino acid system as well as 100 identically parametrized replicas of 100 ns each for an 827 residue T-cell receptor/MHC system. Comparing randomly chosen subgroups within these replica sets, we estimated the reproducibility and reliability that can be achieved by a given number of replicas at a given simulation time. These results demonstrate that conclusions drawn from single simulations are often not reproducible and that conclusions drawn from multiple shorter replicas are more reliable than those from a single longer simulation. The actual number of replicas needed will always depend on the question asked and the level of reliability sought. On the basis of our data, it appears that a good rule of thumb is to perform a minimum of five to 10 replicas.