Piana Stefano, Laio Alessandro
International School for Advanced Studies (SISSA/ISAS), Via Beirut 2-4, Trieste, Italy, and Nanochemistry Research Institute, Curtin University of Technology, GPO Box U1987, Perth 6845, Western Australia.
J Phys Chem B. 2007 May 3;111(17):4553-9. doi: 10.1021/jp067873l. Epub 2007 Apr 10.
By suitably extending a recent approach [Bussi, G.; et al. J. Am. Chem. Soc. 2006, 128, 13435] we introduce a powerful methodology that allows the parallel reconstruction of the free energy of a system in a virtually unlimited number of variables. Multiple metadynamics simulations of the same system at the same temperature are performed, biasing each replica with a time-dependent potential constructed in a different set of collective variables. Exchanges between the bias potentials in the different variables are periodically allowed according to a replica exchange scheme. Due to the efficaciously multidimensional nature of the bias the method allows exploring complex free energy landscapes with high efficiency. The usefulness of the method is demonstrated by performing an atomistic simulation in explicit solvent of the folding of a Triptophane cage miniprotein. It is shown that the folding free energy landscape can be fully characterized starting from an extended conformation with use of only 40 ns of simulation on 8 replicas.
通过适当扩展最近的一种方法[布西，G.；等人，《美国化学会志》，2006年，第128卷，第13435页]，我们引入了一种强大的方法，该方法允许在几乎无限数量的变量中并行重建系统的自由能。在相同温度下对同一系统进行多次元动力学模拟，用在不同组集体变量中构建的随时间变化的势对每个副本进行偏置。根据副本交换方案，定期允许不同变量中的偏置势之间进行交换。由于偏置具有有效的多维性质，该方法能够高效地探索复杂的自由能景观。通过对色氨酸笼状小蛋白在显式溶剂中的折叠进行原子模拟，证明了该方法的实用性。结果表明，从伸展构象开始，仅在8个副本上进行40纳秒的模拟，就可以全面表征折叠自由能景观。
