求助一个审稿人问题，关于熵的贡献

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最近投文章，计算的有机催化反应的机理，以及相应的势能面。结构优化时候就使用溶剂化，势能面的能量使用的是单点能和freq计算中的Thermal correction to Gibbs Free Energy

一审某审稿人对反应中熵的贡献有一些看法。因为是大修，一大堆问题，逐条回复的时候，只是拿文献回答了一下熵的影响实际没有那么大

然后二审回来，发现审稿人其他问题基本没有了，但是还是比较执着于熵的贡献问题。但是我到现在都搞不清楚审稿人这个意见是让添加什么数据？还是让干点什么？希望大家能指导一下

The statement “Based on previous literature (J. Phys. Chem. A 2018, 122, 1392–1399), the contribution of entropy to the reaction is minimal; therefore, it suffices to calculate the free energy using dispersion-corrected DFT functionals” raises some concerns. Firstly, I do not fully agree with the generalization that entropy plays a minimal role in this reaction. Numerous experimental and theoretical studies have highlighted significant differences between potential energy surfaces (PES) and free energy surfaces (FES), especially in large systems (with or without limitd conformational flexibility). Even if part of the system is rigid, the overall system might adopt various conformers with distinct energies when considering the substrate. Secondly, the reasoning that dispersion-corrected DFT functionals alone can account for free energy contributions is unclear—this relates to the level of theory used for energy calculations, not the inclusion of entropic or enthalpic contributions that can be renderd by statistical samplings. Moreover, if entropy is indeed negligible, it is not clear why the authors use (approximate) free energies to correlate NPA charges in intermediate 6, instead of just potential energies.

wzkchem5

我觉得审稿人混淆了entropy和conformational entropy。
基于谐振近似的opt freq，如果只算一个构象的话，可以把entropy里除了conformational entropy以外的部分算得不错。其中如果用QRRHO，可以算得比RRHO更准，用受阻转子模型或VPT2又可以算得比QRRHO更准。但是conformational entropy完全算不出来，等于把conformational entropy当作0来处理。
要算conformational entropy，必须要么做构象搜索，要么做metadynamics等统计采样方法。
所以，首先确保你用的是QRRHO而非RRHO，其次挑几个代表性的反应，把构象搜全，算构象熵及其对自由能的贡献，看构象熵是否可以忽略，就差不多了。不要提色散校正的DFT，这个跟你要说明的问题没有半点关系