Oostenbrink Chris
Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences, Vienna, Austria.
Methods Mol Biol. 2012;819:487-99. doi: 10.1007/978-1-61779-465-0_28.
The one-step perturbation approach offers an efficient means to estimate free energy differences. It may be applied to estimate solvation free energies, conformational preferences or relative free energies of binding of series of compounds to a common receptor. Applicability of the method depends on the possibility to define a proper reference state which may in itself be an unphysical molecule. Here, we describe practical considerations and explicit guidelines to define a proper reference state, and to efficiently calculate relative free energies. The strengths and limitations of the method are highlighted and special considerations are noted. The method may be applied using many different simulation programs. Here, analyses are exemplified at the hand of the GROMOS simulation package.
一步微扰法提供了一种估算自由能差的有效方法。它可用于估算溶剂化自由能、构象偏好或一系列化合物与共同受体结合的相对自由能。该方法的适用性取决于能否定义一个合适的参考态，而这个参考态本身可能是一个非物理分子。在这里，我们描述了定义合适参考态以及有效计算相对自由能的实际考虑因素和明确指导方针。强调了该方法的优点和局限性，并指出了特殊注意事项。该方法可使用许多不同的模拟程序来应用。在这里，以GROMOS模拟软件包为例进行分析。
