Efficient and precise solvation free energies via alchemical adiabatic molecular dynamics
Efficient and precise solvation free energies via alchemical adiabatic molecular dynamics
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DOI：
10.1063/1.2232082
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发表时间：
2006-08-21
影响因子：
4.4
通讯作者：
Tuckerman, Mark E.
中科院分区：
文献类型：
--
作者：
Abrams, Jerry B.;Rosso, Lula;Tuckerman, Mark E.
提出了一种新的分子动力学方法，用于计算与系统的热力学状态或化学组成的变换（也称为炼金术变换）相关的自由能。该新方法扩展了最近由罗索[J. Chem. Phys. 116，4389（2002）]引入的绝热动力学方法，并且基于使用附加的自由度λ，该自由度λ用作表征两种状态的势能函数之间的切换参数。在新的方法中，耦合参数λ被引入作为一个虚构的动力学变量中的哈密顿量，和一个系统的开关函数被采用，导致在相关的热力学端点之间的λ自由能分布的障碍。因此，这种屏障的存在增强了端点（λ =0和λ =1）区域中的采样，这对于计算相关自由能差是最重要的。为了确保有效的势垒跨越，将高温T-lambda分配给lambda，并引入虚拟质量m（lambda）作为在lambda和系统的其余部分之间产生绝热分离的手段。在这些条件下，它示出的lambda自由能分布可以直接计算从绝热概率分布函数的lambda没有任何后处理或unbiasing的输出数据。新的方法说明了两个模型问题，并在TIP 3 P水的氨基酸侧链类似物的溶剂化自由能的计算。与以前的工作相比，使用热力学积分和自由能微扰表明，新的λ绝热自由能动力学方法的结果在非常精确的自由能计算使用显着更短的轨迹。(c)2006年，美国物理学会。
A new molecular dynamics method for calculating free energies associated with transformations of the thermodynamic state or chemical composition of a system (also known as alchemical transformations) is presented. The new method extends the adiabatic dynamics approach recently introduced by Rosso [J. Chem. Phys. 116, 4389 (2002)] and is based on the use of an additional degree of freedom, lambda, that is used as a switching parameter between the potential energy functions that characterize the two states. In the new method, the coupling parameter lambda is introduced as a fictitious dynamical variable in the Hamiltonian, and a system of switching functions is employed that leads to a barrier in the lambda free energy profile between the relevant thermodynamic end points. The presence of such a barrier, therefore, enhances sampling in the end point (lambda=0 and lambda=1) regions which are most important for computing relevant free energy differences. In order to ensure efficient barrier crossing, a high temperature T-lambda is assigned to lambda and a fictitious mass m(lambda) is introduced as a means of creating an adiabatic separation between lambda and the rest of the system. Under these conditions, it is shown that the lambda free energy profile can be directly computed from the adiabatic probability distribution function of lambda without any postprocessing or unbiasing of the output data. The new method is illustrated on two model problems and in the calculation of the solvation free energy of amino acid side-chain analogs in TIP3P water. Comparisons to previous work using thermodynamic integration and free energy perturbation show that the new lambda adiabatic free energy dynamics method results in very precise free energy calculations using significantly shorter trajectories. (c) 2006 American Institute of Physics.