Boresch S, Karplus M
Department of Chemistry, Harvard University, Cambridge, MA 02138, USA.
J Mol Biol. 1995 Dec 15;254(5):801-7. doi: 10.1006/jmbi.1995.0656.
Free energy simulations are of particular interest for the interpretation of macroscopic data in terms of microscopic interactions. This can be done by expressing calculated free energies as a sum of components that correspond to the contributions of different energy terms or different parts of the system. Since the resulting components depend on the integration path, care is required for their use. We show that a linear coupling scheme for the alchemical creation of a chemical identity corresponds to a particularly useful path because it leads to a symmetric decoupling of the free energy components. The path dependence also provides an additional degree of freedom that can be used to study different processes. This latter point is illustrated by a reinterpretation of a recent simulation on wild-type and mutant azurin by Mark and van Gunsteren.
自由能模拟对于根据微观相互作用解释宏观数据特别有意义。这可以通过将计算出的自由能表示为与不同能量项或系统不同部分的贡献相对应的分量之和来实现。由于所得分量取决于积分路径，因此在使用时需要谨慎。我们表明，用于化学身份炼金术创建的线性耦合方案对应于一条特别有用的路径，因为它导致自由能分量的对称解耦。路径依赖性还提供了一个额外的自由度，可用于研究不同的过程。后一点通过对Mark和van Gunsteren最近对野生型和突变型天青蛋白的模拟进行重新解释来说明。
