Radak Brian K, Romanus Melissa, Lee Tai-Sung, Chen Haoyuan, Huang Ming, Treikalis Antons, Balasubramanian Vivekanandan, Jha Shantenu, York Darrin M
Center for Integrative Proteomics Research BioMaPS Institute and Department of Chemistry and Chemical Biology, Rutgers University , Piscataway, New Jersey 08854-8076 United States.
Department of Chemistry, University of Minnesota , Minneapolis, Minnesota 55455-0431, United States.
J Chem Theory Comput. 2015 Feb 10;11(2):373-7. doi: 10.1021/ct500776j.
Replica exchange molecular dynamics has emerged as a powerful tool for efficiently sampling free energy landscapes for conformational and chemical transitions. However, daunting challenges remain in efficiently getting such simulations to scale to the very large number of replicas required to address problems in state spaces beyond two dimensions. The development of enabling technology to carry out such simulations is in its infancy, and thus it remains an open question as to which applications demand extension into higher dimensions. In the present work, we explore this problem space by applying asynchronous Hamiltonian replica exchange molecular dynamics with a combined quantum mechanical/molecular mechanical potential to explore the conformational space for a simple ribonucleoside. This is done using a newly developed software framework capable of executing >3,000 replicas with only enough resources to run 2,000 simultaneously. This may not be possible with traditional synchronous replica exchange approaches. Our results demonstrate 1.) the necessity of high dimensional sampling simulations for biological systems, even as simple as a single ribonucleoside, and 2.) the utility of asynchronous exchange protocols in managing simultaneous resource requirements expected in high dimensional sampling simulations. It is expected that more complicated systems will only increase in computational demand and complexity, and thus the reported asynchronous approach may be increasingly beneficial in order to make such applications available to a broad range of computational scientists.
复制交换分子动力学已成为一种强大的工具，可有效地对构象和化学转变的自由能景观进行采样。然而，要有效地将此类模拟扩展到解决二维以上状态空间问题所需的大量复制品，仍然存在艰巨的挑战。开展此类模拟的支持技术尚处于起步阶段，因此对于哪些应用需要扩展到更高维度仍是一个悬而未决的问题。在本工作中，我们通过应用异步哈密顿复制交换分子动力学结合量子力学/分子力学势来探索一个简单核糖核苷的构象空间，从而研究这个问题空间。这是使用一个新开发的软件框架完成的，该框架仅用足以同时运行2000个复制品的资源就能执行超过3000个复制品。传统的同步复制交换方法可能无法做到这一点。我们的结果表明：1.）即使对于像单个核糖核苷这样简单的生物系统，高维采样模拟也是必要的；2.）异步交换协议在管理高维采样模拟中预期的同时资源需求方面的效用。预计更复杂的系统只会增加计算需求和复杂性，因此所报道的异步方法可能会越来越有益，以便让广大计算科学家能够使用此类应用。
