A Computational Quantum-Based Perspective on the Molecular Origins of Life’s Building Blocks
Round 1
Reviewer 1 Report
Report
A computational quantum-based perspective on the molecular origins of life’s building blocks
Gabriele Amante, Judit E. Sponer, Jiri Sponer, Franz Saija, and Giuseppe Cassone
Manuscript ID: entropy-1725961
In this review article Saija, Cassone and co-workers highlighted the experimental and computational works showcasing the formation of prebiologically relevant molecules such as amino acids and sugars from simple organic and inorganic precursors which could be directly transformed into first biogenic molecules when it was exposed to high-energy sources present in the primordial terrestrial atmosphere. Here, the authors also summarised the key findings obtained from in silico reproduction of breakthrough experiments in the field of prebiotic chemistry such as the Miller-Urey experiment and sugar synthesis from formos reaction, using Ab Initio MD simulation techniques. It is indeed interesting to note that how realistic primordial scenarios are recreated in the in-silico simulation studies using externally applied static and homogeneous electric field (based on the methodology developed by Umari and Pasquarello) and multi-scale shock-compression techniques (MSST). Such studies not only shed light into the key-intermediates like formamide and formic acid molecules, but also the chemical pathways leading to the transformation of simple molecules to complex species, directly associated with the onset of life. Overall, this article is informative and well-written.
I noticed a that this article has significant overlap with a similar review article published by the same research group (Topics in Catalysis (2022) 65:40–58 https://doi.org/10.1007/s11244-021-01487-0). This is a text of the authors and I see no harm in repeating some of it here. Nevertheless, this issue has to be handled by the present Journal in accord with its rules.
Following are the other corrections and misses,
On page 2, in line 44 reference [22?] should be fixed
On page 2, line 61, typo error with “nuclobases”
On page 6, line 241, tupo error with “femtosends”
On page 7 references [5,6,75?] should be fixed
On page 9, line 351, typo error with “formaldehdye aqueous”
On page 10 line 374 reference [61,88?] should be fixed
On page 11 (Figure 2d) probably C-C distance should be added.
Missing key references:
- Soc. Rev. (Tutorial). 47, 5125-5145 (2018)
- Am. Chem. Soc. 142, 12551-12562 (2020).
- SASON SHAIK, THIJS STUYVER (Eds.), Effects of Electric Fields on Structure and Reactivity - New Horizons in Chemistry https://doi.org/10.1039/9781839163043
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Journal: Entropy
Manuscript ID : entropy-1725961
The review entitled “A computational quantum-based perspective on the molecular origins of life’s building blocks” deals with the DFT method coupled to molecular dynamics and used in the modeling of molecular reactions at the origin of life on Earth. This concerns reactions either under an electric field (Miller-Urey, Formosa) or in extreme conditions such as the impact of particles to approximate the impact of meteorites on Earth. A great deal is done about the use of metadynamics methods to better estimate free energy barriers of the species formed. This mini-review is short but condensed. This makes it possible to quickly have a fairly complete state of the art in the field of the AIMD method applied to the molecular reactions which would be at the origin of life on Earth. Despite the use of chemistry under an electric field, the term electrochemistry does not appear, and yet that is what it is all about. It is true that this is not mentioned too much in the literature. I propose to add the reference (JACS 2019) on the electropolymerization of amino acids, an extension of Miller-Urey reactions mixing experiements, AIMD and metadynamics. I give a favorable opinion to the publication of this interesting work on the condition of taking into account my comments below.
Comments / suggestions
1. In your introductory part, which is quite exhaustive on the chemistry of the different building blocks of life, something is missing about amino acids. Once concentrated (more concentrated than that found in Miller-Urey experiments), they can be electropolymerized into peptides. In addition to Saitta et al. (your ref [39]), modeling of electropolymerization by AIMD simulation in the ESM framework is included in ref. https://doi.org/10.1021/jacs.9b05910, which is suitable for your minireview topic. Please add this reference that is a plausible path to peptide route too. Electrochemistry is another way to produce prebiotic molecules at charged interfaces (cf for instance https://doi.org/10.1098/rsfs.2019.0073), in addition to sparkles used by Miller-Urey reactions.
2. The problem of the electric field and the periodicity of the simulation box is well mentioned, p. 3. The ESM (effective screening medium) method which precisely overcomes this problem too is not mentioned. The ESM method exists in Quantum Espresso, SIESTA and OpenMX-square. A small paragraph on this subject would be welcome to reinforce your review: https://sugino.issp.u-tokyo.ac.jp/esm/
3. p.7 there is ? with ref. [5,6,75?] just above reaction (6).
4. P. 9, l. 307, please correct portmanteu -> portmanteau
5. The NVT conditions, mentioned in part 2.2, are rather for reactions under mild conditions with an electric field applied or not. It would also be relevant to briefly recall the conditions used for the collision simulations presented in part 3.3 (P, T, velocity of atoms at the beginning of the simulation, for instance).
6. P. 15, l. 540, please correct “Thus, by adding an history” -> a history
Author Response
Please see the attachment.
