Coupling of replica exchange simulations to a non-Boltzmann structure reservoir
Coupling of replica exchange simulations to a non-Boltzmann structure reservoir
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DOI：
10.1021/jp068335b
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发表时间：
2007-03-15
影响因子：
3.3
通讯作者：
Simmerling, Carlos
中科院分区：
文献类型：
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作者：
Roitberg, Adrian E.;Okur, Asim;Simmerling, Carlos
对于大型生物分子来说，计算融合的整体特性仍然具有挑战性。复制交换分子动力学（REMD）可以通过使用高温来逃避动力学陷阱，从而显着提高构象采样的效率。包括我们在内的几个小组引入了将副本交换耦合到预收敛、玻尔兹曼填充的储层的想法，通常温度高于最高温度副本的温度。此过程降低了计算成本，因为仅针对单个温度进行大量采样所需的长模拟时间。然而，该方法的一个弱点是玻尔兹曼加权储层仍然难以生成。我们现在提出使用非玻尔兹曼储库的想法，其结构可以通过更有效的构象采样方法生成。我们证明了该方法是严格的，并得出了储层和副本之间正确的统计机械交换标准，该标准驱动副本的玻尔兹曼加权概率。我们在 trpzip2 肽上测试了这种方法，并证明所得到的热稳定性曲线与使用很长（> 100 ns）标准 REMD 模拟获得的热稳定性曲线基本上没有区别。这种油藏辅助 REMD 的收敛速度明显快于常规 REMD。此外，我们证明了交换标准的修改是必要的；使用标准交换函数和非玻尔兹曼储层的 REMD 模拟产生了错误的结果。
Computing converged ensemble properties remains challenging for large biomolecules. Replica exchange molecular dynamics (REMD) can significantly increase the efficiency of conformational sampling by using high temperatures to escape kinetic traps. Several groups, including ours, introduced the idea of coupling replica exchange to a pre-converged, Boltzmann-populated reservoir, usually at a temperature higher than that of the highest temperature replica. This procedure reduces computational cost because the long simulation times needed for extensive sampling are only carried out for a single temperature. However, a weakness of the approach is that the Boltzmann-weighted reservoir can still be difficult to generate. We now present the idea of employing a non-Boltzmann reservoir, whose structures can be generated through more efficient conformational sampling methods. We demonstrate that the approach is rigorous and derive a correct statistical mechanical exchange criterion between the reservoir and the replicas that drives Boltzmann-weighted probabilities for the replicas. We test this approach on the trpzip2 peptide and demonstrate that the resulting thermal stability profile is essentially indistinguishable from that obtained using very long (> 100 ns) standard REMD simulations. The convergence of this reservoir-aided REMD is significantly faster than for regular REMD. Furthermore, we demonstrate that modification of the exchange criterion is essential; REMD simulations using a standard exchange function with the non-Boltzmann reservoir produced incorrect results.