JMIRxMed JMIRx Med JMIRx Med 2563-6316 JMIR Publications Toronto, Canada v2i3e33215 10.2196/33215 Peer-Review Report Peer-Review Report Peer Review of “Selection of the Optimal L-asparaginase II Against Acute Lymphoblastic Leukemia: An In Silico Approach“ Meinert Edward Hardikar Navneetha BSc 1 https://orcid.org/0000-0002-4215-8864 Department of Biology Queen's University Kingston, ON Canada Jul-Sep 2021 8 9 2021 2 3 e33215 27 8 2021 27 8 2021 ©Navneetha Hardikar. Originally published in JMIRx Med (https://med.jmirx.org), 08.09.2021. 2021

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 https://www.biorxiv.org/content/10.1101/2020.10.13.337097v1 https://preprints.jmir.org/preprint/29844 https://med.jmirx.org/2021/3/e33217/ https://med.jmirx.org/2021/3/e29844/

This is a peer-review report submitted for the paper “Selection of the Optimal L-asparaginase II Against Acute Lymphoblastic Leukemia: An In Silico Approach”.

Round 1 Review General Comments

This paper [1] aimed to investigate whether asnB from E Coli and Erwinia is the best asparaginase for the therapeutic treatment of acute lymphoblastic leukemia by using asnB sequence of E Coli to search for homologous proteins in other bacteria and archaea phyla. The authors mention that asnB with the lowest Michaelis Menten constant (Km) and the lowest immunogenicity is to be considered the most suitable enzyme. A phylogenetic tree was created, after which homology modeling was conducted, followed by docking to identify the binding energies to determine the relationship between binding energy and Km. The technical aspects of the paper are adequately conveyed, and the in silico method is appropriate to answer the question. However, I have a few comments that need to be clarified.

 Specific Comments Major Comments

Perhaps, explain what blastp does to provide more insight.

It would be beneficial to include a figure that displays the sequence alignment of the query sequence along with the similarity percentage.

The discussion is well-written, although could benefit from including other relevant studies/prior works to support your results.

Conclusion is relatively weak. Please consider revising it and sufficiently summarizing the Methods and Results.

 Minor Comments

Section 2.2: Please define DOPE and SOAP before abbreviating.

Discussion: It is mentioned that only 6 of 10 species could have a Km value assigned to a certain sequence, please mention these 6 species.

Discussion: The sentence “Thus it can be predicted that an enzyme with better kinetics that currently commercially available asparaginase can be cloned from Streptomyces species” is a bit ambiguous. Please rewrite this sentence.

 Round 2 Review General Comments

The authors have addressed all reviewer comments and improved the manuscript. I have no further comments.

No conflict declared.

 Baral A Gorkhali R Basnet B Koirala S Bhattarai HS Selection of the optimal L-asparaginase II against acute lymphoblastic leukemia: an in silico approach JMIRx Med 2021 09 7 2 3 e29844 10.2196/29844