Department of Chemistry, Texas A&M University, College Station, Texas 77843, USA.
J Chem Phys. 2009 Dec 7;131(21):214109. doi: 10.1063/1.3266563.
In this paper, based on the integrated tempering sampling we introduce a selective integrated tempering sampling (SITS) method for the efficient conformation sampling and thermodynamics calculations for a subsystem in a large one, such as biomolecules solvated in aqueous solutions. By introducing a potential surface scaled with temperature, the sampling over the configuration space of interest (e.g., the solvated biomolecule) is selectively enhanced but the rest of the system (e.g., the solvent) stays largely unperturbed. The applications of this method to biomolecular systems allow highly efficient sampling over both energy and configuration spaces of interest. Comparing to the popular and powerful replica exchange molecular dynamics (REMD), the method presented in this paper is significantly more efficient in yielding relevant thermodynamics quantities (such as the potential of mean force for biomolecular conformational changes in aqueous solutions). It is more important that SITS but not REMD yielded results that are consistent with the traditional umbrella sampling free energy calculations when explicit solvent model is used since SITS avoids the sampling of the irrelevant phase space (such as the boiling water at high temperatures).
在本文中，我们基于集成回火抽样法，引入了一种选择性集成回火抽样（SITS）方法，用于对大型体系（如水溶液中的生物分子）中的子系统进行高效的构象抽样和热力学计算。通过引入一个与温度相关的势能表面，选择性地增强了感兴趣的构象空间（例如，溶剂化的生物分子）的抽样，而系统的其余部分（例如，溶剂）则基本不受干扰。该方法在生物分子体系中的应用允许在能量和感兴趣的构象空间上进行高效的抽样。与流行且强大的复制交换分子动力学（REMD）相比，本文提出的方法在生成相关热力学量（例如水溶液中生物分子构象变化的平均力势能）方面效率更高。更重要的是，当使用显式溶剂模型时，SITS 而不是 REMD 产生的结果与传统的伞状抽样自由能计算结果一致，因为 SITS 避免了对不相关相空间（例如高温下的沸水）的抽样。
