DNA Gene’s Basic Structure as a Nonperturbative Circuit Quantum Electrodynamics: Is RNA Polymerase II the Quantum Bus of Transcription?

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

 

Aroche et al. studied the DNA gene's basic structure as a nonperturbative circuit quantum electrodynamics, focusing on whether RNA polymerase II is the quantum bus of transcription. The topic is of great interest to the scientific community. However, the manuscript has several issues.  

1.      The manuscript has multiple issues in the mathematical equations that the authors have written. Equation 11 is plain wrong. The authors replaced ‘e’ with ‘q’ and mentioned that ‘q’ is the electron charge. The ‘e’ in the original well-established formalism is not an electron charge, but it is to denote exponential. Mixing symbols and equations in different contexts may result in new formalism, but it may not be physical.

2.      The authors claimed that it is a quantum electrodynamic approach. Based on this argument, the authors want to discuss DNA at the electron’s dynamic level. However, they have not discussed that depth in the manuscript at all, and they are apparently not aware of electron-electron interaction at all. The authors are concentrating on a semi-classical level, but the study is incomplete.

3.      The authors have notations clash in the manuscript.

4.      The authors introduced a creation/annihilation operator without proper analysis.

5.      The authors should be aware that their system should have exciton dynamics when they assume creating an electron-hole pair.

6. There are numerous typographical errors. Please see the attached annotated PDF.

The literature review part of the manuscript looks good. However, I strongly recommend that the authors revisit quantum electrodynamics and its application to macromolecules such as DNA and RNA.

Comments on the Quality of English Language

There are numerous typographical errors. Mathematical presentation needs improvement.

Author Response

Dear Editor, please see the attachment. We are very grateful for the time spent reviewing our work. Thank you very much for all the comments. They have undoubtedly greatly enriched the quality of our work.

Reviewer 2 Report

Comments and Suggestions for Authors

This is a potentially interesting paper, but is not an appropriate paper for CIMB, despite "molecular biophysics" appearing in CIMB's Aims & Scope.  Readers of CIMB cannot be expected to know what Josephson Junctions or transmon waveguides are, to know anything about (or to have even heard of) cavity QED, or to comprehend complicated strings of formalism like Eq. 1 (p. 6).  This may be unfortunate; I for one agree with the authors than much of biology is incomprehensible from a classical-physics perspective.  But the current paper, which carefully explains the structure of DNA and how Pol II works (p. 2 - 3) but just assumes that readers already know what JJs and SQUIDs are, doesn't help matters in this regard.

The paper needs, in other words, to be submitted to a physical biochemistry journal or someplace like Phys. Rev. E, where both reviewers and likely readers will be able to critically evaluate its contents.

Prior to resubmission anywhere, however, there are some major issues to be addressed.

1.  Models like this one inevitably raise questions about decoherence or, rather, how quantum coherence is maintained where it needs to be for the model to make sense.  The authors say in the abstract that "RNA polymerase II produces decoherence during transcription" and repeat this same phrase in the Conclusion (p. 17), but they never what is decohered or more importantly, what prevents decoherence of the whole system of interest.  The un-numbered equation at the bottom of p. 10 a decoherence term H_gamma and a (presumably classical) loss term H_k, but there is no explanation of what these look like, only a remark in the caption to Fig. 3 that the coupling g has to be much larger than the effective couplings gamma or k (both are indeed set equal to zero in Fig. 3).

The question, of course, is *why* these loss terms are small.  What about the structure of DNA and its coupling to its environment minimizes decoherence of H-bond quantum states?  The authors are appealing to resonator theory, but how does this connect to the biology or the physical chemistry of the DNA-cytosol system?  Are there some kind of assumptions about structured water, or something else that's meant to form a quantum insulator that effectively isolates the qubits of interest?  The A-T and G-C base pairs are themselves very large systems compared to an H-bond; what "rigidifies" these molecules enough that coherence in not lost into the multi-electron states of the nucleotide bases?

The whole model rests on the answers to these questions and others like them, pertaining to each possible source of extraneous coupling.  What the system is, what its environment is, and what their interaction is, and why this interaction is small enough to prevent decoherence of the qubits of interest need to be explained.  It's not enough to postulate a formal model taken from some other domain involving completely different materials and physical conditions.  An explanation of why the chosen model plausibly applies to a warm, wet biochemical system is also required.

2.  How and where the action of pol II induces decoherence, and how the structure of pol II spatially limits decoherence needs to carefully explained.  For example, if the pol II CTD is "flexible and highly disordered" (p. 14), how can it protect qubits upstream and downstream from the nucleotide addition site from decoherence?  A much better explanation of Fig. 1 is needed; what "a rotation of the point on the sphere concerning the rotation axis at the rotation angle" (Fig. 1 caption) means, for example, is utterly unclear.  Fig. 1B appears to plot sin functions, but the caption refers to sin^2 functions.  How these "reproduce" a Bloch sphere (a pure single-qubit state space) needs to be explained.

3.  The formalism throughout is insufficiently described.  Equations are taken from various references, but what the terms in these equations actually mean in the molecular setting is not explained.  There are also, unfortunately, a lot of fuzzy boxes in equations (e.g. bottom of p. 8) where some symbol font is unreadable by whatever software generated the pdf.  All of this needs to be fixed, and all the equations need to be numbered so that future reviewers can refer to them unambiguously.

Author Response

Dear Editor, please see the attachment. We are very grateful for the time spent reviewing our work. Thank you very much for all the comments. They have undoubtedly greatly enriched the quality of our work.

Reviewer 3 Report

Comments and Suggestions for Authors

According to abstract, Authors discussed how a quantum information transfer protocol and entanglement can be achieved by modeling DNA as a combination of n nonperturbative circuits quantum electrodynamics with nine Radio Frequency- Superconducting Quantum Interference Devices (termed as SQUIDs).

Unfortunately, in my opinion, the current version of the manuscript requires further effort to improve the quality of the presentation of the results and the text of particle should be also improved. An exceptionally enormous number of typos and undefined notions can be identified in the work, e.g.:

+ page 2, single line has text: „DNA AND TRANSCRIPTION: STRUCTURAL AND BIOCHEMICAL STUDIES”, it is caption or subsection title?

+ page 3, Figure 1, show how to encode qubit state from Bloch Sphere, but Figure show only circle/ellipsis, the true nature of qubit is 3D Bloch sphere, with complex number, description of qubit only with real circle is not complete,

+ qubit state rewriting system shown at page 4 and 5, need further explanation, because first line: |0⟩[𝐴 𝑇 ] = |0⟩[𝑇 𝐴 ] = |0⟩[𝑋], and |1⟩[𝐺 𝐶 ] = |1⟩[𝐶 𝐺 ] = |1⟩[𝑌] is not clear how to define the second example on the page 5:

|𝜓⟩𝐴 = |𝜓⟩𝐺 = |0⟩, and |𝜓⟩𝑇 = |𝜓⟩𝐶 = |1⟩, then

|0⟩[𝑋] = |0⟩[01] or |0⟩[10], and |1⟩[𝑌] = |1⟩[01] or |1⟩[10]

|𝜓⟩𝐴𝑇 = [00], |𝜓⟩𝑇𝐴 = [01], |𝜓⟩𝐶𝐺 = [11], and |𝜓⟩𝐺𝐶 = [10]

In paper such definition should be exposed in precisely defined in current form such rewriting in not clear. How we rewrite sequence |𝜓⟩𝑇𝐴 into [01], why equal sign is used in all cases. In such cases as rewriting system more adequately we should use the congruence or equivalence symbols.

The page 5 contains sentence: Josephson Equation 𝐼𝑠 = 𝐼0.𝑠𝑖𝑛 𝑠𝑖𝑛 (∅2 - ∅1) why Authors use the double sin function (or exp exp in other equations). The special meaning of dot between I0 and sin is also not defined. Similar use of cos function can be also founded at page 6. Equation on the page, the bottom of page has empty square, probably is not finished. Similar errors also can be found on the page 9. More typos at equations can be also found at page 13 where limits on integrals are also omitted.

Authors also did not show clearly how, for example, the Hamiltonians presented on page 12 are transcribed into the right DNA sequences. There is no clear and straightforward example of how Hamiltonian dynamics is represented by DNA rewriting phenomena.

Again, on the page 10 we have text “DNA AS A QUANTUM ELECTRODYNAMIC CIRCUIT. THE HAMILTONIAN SCHEME” which is caption or subsection title.

Abstract of paper suggest that entanglement phenomenon is discussed in the paper, but problem of entanglement finally is not discussed in the paper.

Therefore, despite a remarkably interesting problem that was taken up by Authors, in current form of the reviewed paper I cannot recommend publication of reviewed article. Authors should prepare an updated version of their work with improved presentation, typesetting and error correction in equations.

Author Response

Dear Editor, please see the attachment. We are very grateful for the time spent reviewing our work. Thank you very much for all the comments. They have undoubtedly greatly enriched the quality of our work.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors addressed my concerns to a reasonable extent. However, the manuscript still needs to be significantly polished. The science looks good now.

Comments on the Quality of English Language

I strongly recommend the authors proofread the manuscript multiple times.

Author Response

Dear Editor,

We are very grateful for all your suggestions, which significantly improved the content and form of this document. We sincerely regret any inconvenience. Thank you very much for your time and all the effort invested.  

Please let us know if you want us to review the document again. All your comments were valuable. We appreciate them

Best wishes and blessings  

 

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for your explanation.  I still find your paper very difficult to understand, but am happy to defer to the editor regarding suitability for CIMB.  I do appreciate the difficulty of explaining a complicated analysis in a single paper, so I will not insist on further changes.

Author Response

Dear Editor, 

We are very grateful for all your suggestions.  We are very sorry for any inconvenience caused. We greatly appreciate your time.

I agree with the degree of difficulty of the information presented. 

It isn't straightforward to explain in a single document.

We appreciate the opportunity to have the editor-in-chief decide on the document's suitability for the journal.

We are very thankful. 

Best wishes!   

Reviewer 3 Report

Comments and Suggestions for Authors

Authors answered on technical remarks raised at the first review, so I do not raise other remarks.  Technical quality of paper is significantly improved.

Author Response

Dear Editor, 

We are very grateful for all your suggestions, time, and acceptance of the document's final version.

Best wishes!