Matsunaga Yasuhiro, Kamiya Motoshi, Oshima Hiraku, Jung Jaewoon, Ito Shingo, Sugita Yuji
Graduate School of Science and Engineering, Saitama University, Saitama, Saitama 338-8570 Japan.
Institute for Molecular Science, Myodaiji, Okazaki, Aichi 444-8585 Japan.
Biophys Rev. 2022 Dec 14;14(6):1503-1512. doi: 10.1007/s12551-022-01030-9. eCollection 2022 Dec.
Multistate Bennett acceptance ratio (MBAR) works as a method to analyze molecular dynamics (MD) simulation data after the simulations have been finished. It is widely used to estimate free-energy changes between different states and averaged properties at the states of interest. MBAR allows us to treat a wide range of states from those at different temperature/pressure to those with different model parameters. Due to the broad applicability, the MBAR equations are rather difficult to apply for free-energy calculations using different types of MD simulations including enhanced conformational sampling methods and free-energy perturbation. In this review, we first summarize the basic theory of the MBAR equations and categorize the representative usages into the following four: (i) perturbation, (ii) scaling, (iii) accumulation, and (iv) full potential energy. For each, we explain how to prepare input data using MD simulation trajectories for solving the MBAR equations. MBAR is also useful to estimate reliable free-energy differences using MD trajectories based on a semi-empirical quantum mechanics/molecular mechanics (QM/MM) model and ab initio QM/MM energy calculations on the MD snapshots. We also explain how to use the MBAR software in the GENESIS package, which we call , for the four representative cases. The proposed estimations of free-energy changes and thermodynamic averages are effective and useful for various biomolecular systems.
多态贝内特接受率（MBAR）是一种在分子动力学（MD）模拟完成后分析模拟数据的方法。它被广泛用于估计不同状态之间的自由能变化以及感兴趣状态下的平均性质。MBAR使我们能够处理从不同温度/压力下的状态到具有不同模型参数的各种状态。由于其广泛的适用性，MBAR方程在使用包括增强构象采样方法和自由能微扰在内的不同类型MD模拟进行自由能计算时相当难以应用。在本综述中，我们首先总结MBAR方程的基本理论，并将代表性用法分为以下四类：（i）微扰，（ii）缩放，（iii）累积，以及（iv）全势能。对于每一类，我们解释如何使用MD模拟轨迹准备输入数据以求解MBAR方程。MBAR对于基于半经验量子力学/分子力学（QM/MM）模型的MD轨迹以及对MD快照进行的从头算QM/MM能量计算来估计可靠的自由能差异也很有用。我们还解释了如何在GENESIS软件包中使用我们称为 的MBAR软件来处理这四类代表性情况。所提出的自由能变化和热力学平均值的估计对于各种生物分子系统是有效且有用的。
