Hi. I just got done reading your paper about as carefully as I could in a couple hours. I wanted to first say I really like it; it's nice to have such a specific and detailed report to showcase the inherent problems in trying to make mechanistic predictions based on an entropy-corrected continuum-solvated PES. The prevalence/acceptance of such work really bothers me. Also there is no doubt in my mind that we are not in a position to make any reliable prediction without experimental assistance, and I read your comments on entropy correction methods with a smile.
On the other hand, it really seems that the paper conflates computational modelling with these (usually DFT) structural studies. This then paints all modelling as being subject to these flaws which is not true - a huge chunk of computational approaches have been ignored. I know studies are done that take great care to compute free energies for different pathways via an empirical or semi-empirical PES with significant sampling and explicit inclusion of large amounts of solvent, often including the explicit solvent-reactant proton transfers that get left out of the QM studies. I would be glad to hear your opinion on the utility of these types of calculation too (and if possible why your paper doesn't seem to mention them).
I realise your paper specifically does not get into computation-denigrating like the C&EN article does (the awfulness of the article prompted me to read your paper and comment), but it seems they take your words and use them against all computational methods. I also wonder how you feel about the article personally? I think Ken Houk's comments really follow what I thought, that QM/continuum solvent methods are known to not be capable of getting things correct alone (athough I've argued with his students about their claims regarding solution mechanisms based on DFT/PCM calculations and they couldn't explain to me why they felt comfortable extrapolating from a PCM study to bulk or 'reality'.
Finally, I want to ask if you had a set of readers in mind when you did this work? I would guess most people I know in the field are aware of the general thrust of your paper and would dismiss those papers you do so well in showing the problems with out of hand. I am concerned that my opinion is biased because of who I have worked with though. Is that your experience too or do you think the wider community needs this point to be made so hard? Do you hope this helps with the 'black-box' problem we have in the field?
Anyway, if you don't have time to answer, thanks for doing some excellent work.