This paper describes a new database that is likely to be of substantial interest and value to the scientific community. The work appears basically sound, but might benefit from some clarification and enhancements, including in relation to the validation statistics, as now detailed.

The attention to validation of the modeled structures is very welcome, but perhaps a little unclear. For example, text on page 8 says the models were tested against 7,012 experimental structures, but I am not sure what the results of these tests were. The text does says the results were validated for 952 reaction set IDs, but I'm not sure how this relates to the 7,012 cases. What fraction of tests were passed, and what was the definition of passing? Perhaps this is stated, and I missed it.

Also, on page 9, a median distance between predicted and actual pocket locations of 6 A does not sound that good, but the ligand RMSDs reported in Figure 8 seem quite good. It might be helpful to clarify the relationship between these figures of merit. Also, please clarify the dataset plotted in Figure 8. Is this for the 7,012 structures mentioned above?

Finally, regarding the database itself, I think that entries, such as http://www.brylinski.org/pub/eModelBDB.php?reactant_set_id=00267770, would be improved by including the source organism and common name of the protein and possibly its amino acid sequence; a SMILES and/or INCHI string of the compound; and possibly the IDs of the PDB structure(s) used to build the model. This added information would make each entry more self-contained, rather than requiring users to refer back to the PDB and BindingDB for this basic information.

Are the methods appropriate to the aims of the study, are they well described, and are necessary controls included? If not, please specify what is required in your comments to the authors.
Yes

Are the conclusions adequately supported by the data shown? If not, please explain in your comments to the authors. Yes

Does the manuscript adhere to the journal’s guidelines on minimum standards of reporting? If not, please specify what is required in your comments to the author
No

Are you able to assess all statistics in the manuscript, including the appropriateness of statistical tests used? (If an additional statistical review is recommended, please specify what aspects require further assessment in your comments to the editors.)
No, I do not feel adequately qualified to assess the statistics.

Quality of written English Please indicate the quality of language in the manuscript:
Acceptable

Declaration of competing interests Please complete a declaration of competing interests, consider the following questions: Have you in the past five years received reimbursements, fees, funding, or salary from an organization that may in any way gain or lose financially from the publication of this manuscript, either now or in the future? Do you hold any stocks or shares in an organization that may in any way gain or lose financially from the publication of this manuscript, either now or in the future? Do you hold or are you currently applying for any patents relating to the content of the manuscript? Have you received reimbursements, fees, funding, or salary from an organization that holds or has applied for patents relating to the content of the manuscript? Do you have any other financial competing interests? Do you have any non-financial competing interests in relation to this manuscript? If you can answer no to all of the above, write ‘I declare that I have no competing interests’ below. If your reply is yes to any, please give details below.
I declare that I have no competing interests.

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I agree to the open peer review policy of the journal

Authors' response to reviews: (https://drive.google.com/open?id=1cGlZXX7ZyuOYCsl-uZ_C3cDpkbLfo6Sb)