Understanding the Origin of Structural Diversity of DNA Double Helix

Round 1

Reviewer 1 Report

Authors have performed an extensive study on the optimization and conformation generation for several dinucleosides using quantum calculations. While I like the voluminous approach of the particular work, I have several comments and suggestions regarding the presentation of the work. I state them below.

1. Authors uses several acronyms such as dDMP, cdDMP, SPB, WCD, NtC etc. Since they are defined only once, it is really hard to read the manuscript at a later stage, especially when somebody doesnot immediately finish reading the MS and resume it from the middle.
2. This MS clearly is a continuation of a previous report by some of the authors and the manuscript refers to it often. This makes the MS dependent on a previous one. I strongly suggest authors to include essential information. For example, definition of NtC is not given (referred) along with the NtC codes such as BB00, BB01. While only few of the structures are given, it makes it really difficult to visualize the important differences in these conformations. 
3. 'Superposition of bases' and superposition pattern etc. are mentioned quite often. However, they are never explained in this manuscript. 
4. DFT functionals are mentioned, but not the basis sets
5. Energy is not given for any of the optimized structure. Moreover, optimization criteria (force or energy tolerance) is not given
6. The tables of results are not useful to understand which conformations to rely on. For example, BB00 has soe may different values of each of the dihedrals. Which one should one take. Pictorial description based on distribution of these dihedrals will make the understanding much easier.
7. Authors have assumed that readers would know what are BI, BII, AI etc. conformations. This really restricts the readership. A context should be given in the introduction or in the method section.
8. Authors have taken structures from PDB or NDBs which are often crystallized in the presence of water. However, water was not used in the optimization. An explanation is required.
9. Also, authors have mentioned that more than one local minima are obtained. How did they choose which optimization to consider?
10. Finally, since it is a detailed study on the conformations of various dinucleosides, authors should put these in the context of larger structure of DNA and RNAs and compare the conformations obtained here versus that are present in various experimentally deduced structures. 
11.  

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

The manuscript discusses a structural diversity of DNA double helixes basing on the results of numerous quantum chemical and molecular mechanical calculations. I would like specially highlight the wide choice of quantum-chemical and molecular mechanic  approximations used in the manuscript. This makes the presented data to be more evidential.

I have only some technical issues which  have to be addressed by authors.

1. There is not clear for me how the data presented in table 1 are averaged.

2.I suggest discussing in more details the results presented in the following publications? Since they have direct relation to the subject discussed by authors (Phys Chem Chem Phys 2012 28;14(44):15257-77, doi: 10.1039/c2cp41987d, J Biomol Struct Dyn2004 Feb;21(4):537-54.doi: 10.1080/07391102.2004.10506947, J Biomol Struct Dyn2004 Oct;22(2):227-44.doi: 10.1080/07391102.2004.10506998.

Author Response

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Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Authors have modified the manuscript based on the suggestions and also answered all my questions.