Glycosidic vs. Aglycol Form of Natural Products as Putative Tyrosinase Inhibitors
Round 1
Reviewer 1 Report
The Article is very interesting and has its merits. However, there are two significant flaws which needs to be addressed before publication.
- From the article it can be concluded that only one trajectory was performed. Single trajectory has no statistical significance, therefore at least additional trajectories should be performed.
- The simulation box was +8Å which is rather small box with 10Å cutoff. Just in case Authors should check the final snapshot for mirror image interactions.
There are also minor issues:
- "as well as Ho atoms were discarded" the Ho is ambiguous and Authors should explain what they mean.
- AutoDock version is missing.
- The copper model used in MD should be discussed more extensively.
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The manuscript ID biophysica-1467293 entitled “Glycosidic vs aglycol form of natural products as putative tyrosinase inhibitors” is quite an interesting study submitted to the journal Biophysica.
Numerous natural products and designed molecules have been evaluated as tyrosinase inhibitors that impede the enzyme’s oxidation activity. In the present study, new potent natural inhibitors were retrieved from the ZINC database by similarity screening of previously reported tyrosinase inhibitors. The candidate inhibitory molecules were categorized into groups and subsequently, Molecular docking studies against the tyrosinase structure from Agaricus bisporus were carried out. The results suggested that the glycosylated inhibitors could interact better with the enzyme than their aglycon forms. In order to further examine the role of the sugar side group of potent tyrosinase inhibitors, the dynamic behavior of two such pairs of glycosidic - aglycol form (naringin-naringenin and icariinicaritin) in their complex with the enzyme were studied by means of 20-ns MD simulation. Both docking and MDs analyses showed that the glucoside molecules naringin and icariin form more stable complexes with tyrosinase, thus being more potent inhibitors. However, the following questions should be addressed before submitting a revision.
- In the abstract, the author might highlight their study results. There is more general info here. Re-write properly.
- Introduction: What are the pros and cons of synthetic glucoside-based inhibitors? What is the need for screen natural products?
- Page 2: line 47 to 52 is not clear. The authors may provide the hypothesis, aim, and summary at the end of the intro might be meaningful.
- Methods: What are chemical characteristics were used for ligand selection?
- What is the Tanimoto- Combo score? How is it reliable for ligand screening?
- AbTYR PDB ID? Which tool is used to prepare protein?
- How the free energy of binding (FEB) and fit quality (FQ) were estimated? Formula?
- The author stated “four 3D models corresponding to AbTYR complexes with naringin, naringenin, icariin, and icaritin molecules were obtained from previous docking analysis” need to mention complex PDB ID---is it crystallographic or modeled?
- Table 1, does not provide any meaningful info---authors may merge with other Tables having relevant info
- How do the authors calculate Ki? Include formula
- Figure 2: how about the hydrogen and other bond distances? What is the importance of different interactions, describe in detail
- What is the info extracted from CoM (Center of Mass) and RoG graphs?
- In figure 3, h-bond distances above 2.5 are considered as weak interaction, then how that interaction able to react with a receptor in a stable manner?--- describe in detail
- Discussion and conclusion might be improved otherwise this study is meaningless.
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
The paper can be accepted in present form, however, the second trajectory would significantly improve the quality of paper.
Reviewer 2 Report
The authors addressed all the queries raised by the reviewer. The present form is suitable for publication.
