search

ramess101 / JCED_FOMMS_Manuscript

0 stars 1 forks source link

Reviewer 3 Comment 3 #32

Open ramess101 opened 5 years ago

ramess101 commented 5 years ago

@mrshirts @jpotoff @msoroush

For polar molecules, do the authors anticipate that the GCMC-MBAR approach will be capable of parametrizing the electrostatic charges with a similar efficiency as it can be done for the non-polar interactions?

The GCMC-MBAR method is applicable to parameterizing electrostatic charges, although it is unknown if GCMC-MBAR will be as reliable over a wide range of charge values. From an optimization standpoint, fitting charges and van der Waals parameters simultaneously can lead to a multi-modal problem which might require MBAR to explore very large regions of parameter space to hop between local optima. I am not sure we need to discuss the optimization aspect, but maybe we should just leave electrostatics as future work.

jpotoff commented 5 years ago

@ramess101 If MBAR could do it in principle, it would be fine to say it can, but evaluating the efficiency would require an entirely new study (new water model anyone?) that is beyond the scope of this work.

ramess101 commented 5 years ago

@jpotoff

I agree. But no, I am not brave/crazy enough to take on developing a new water model

jpotoff commented 5 years ago

I agree. But no, I am not brave/crazy enough to take on developing a new water model

LOL.

mrshirts commented 5 years ago

I am not sure we need to discuss the optimization aspect, but maybe we should just leave electrostatics as future work.

It can be phrased more generally. If there is overlap, it will work. MBAR works locally very well, doesn't extend globally because of lack of overlap in phase space. (We are working on how to use the MBAR estimates to extrapolate further in a systematic way - but that's beyond this paper, and shouldn't even be mentioned (too hypothetical at this point).

ramess101 commented 5 years ago

@mrshirts @jpotoff @msoroush

Not entirely satisfied with this response. Suggestions welcomed.

image

ramess101 commented 5 years ago

@mrshirts @jpotoff @msoroush

I decided to just include a short paragraph at the end of the discussion section to address fitting electrostatic charges. Here is my modified response:

image

mrshirts commented 5 years ago

You could cite https://pubs.acs.org/doi/abs/10.1021/acs.jctc.5b00869 as an example of using MBAR for electrostatics and vdW simultaneously.

ramess101 commented 5 years ago

@mrshirts

Perfect!

ramess101 commented 5 years ago

@mrshirts

Were you OK with the wording for this response?

image