CoChat
Sign Up
Cited by 26Origins and Evolution of LifeSpace Science and Extraterrestrial LifeRNA and protein synthesis mechanisms

Exploring astrobiology using in silico molecular structure generation

Open access
Meringer, Markus, Cleaves, H. James·2017·Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences
DOI 10.1098/rsta.2016.0344PMC PMC5686402
Open this paper in CoChat — free accountOpen PDF

Abstract

The origin of life is typically understood as a transition from inanimate or disorganized matter to self-organized, ‘animate’ matter. This transition probably took place largely in the context of organic compounds, and most approaches, to date, have focused on using the organic chemical composition of modern organisms as the main guide for understanding this process. However, it has gradually come to be appreciated that biochemistry, as we know it, occupies a minute volume of the possible organic ‘chemical space’. As the majority of abiotic syntheses appear to make a large set of compounds not found in biochemistry, as well as an incomplete subset of those that are, it is possible that life began with a significantly different set of components. Chemical graph-based structure generation methods allow for exhaustive in silico enumeration of different compound types and different types of ‘chemical spaces’ beyond those used by biochemistry, which can be explored to help understand the types of compounds biology uses, as well as to understand the nature of abiotic synthesis, and potentially design novel types of living systems. This article is part of the themed issue ‘Reconceptualizing the origins of life’.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1098/rsta.2016.0344

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • With a much larger amphiphile diversity, say NG = 106, much larger assemblies such as small (0.2 μm) vesicles might portray replication/reproduction behaviour.

    “With a much larger amphiphile diversity, say NG = 106, likely to prevail at life's origin [45], much larger assemblies, such as small (0.2 µm) vesicles (a size consistent with total molecular count of 106), might portray replication/reproduction behaviour.”

    From Systems protobiology: origin of life in lipid catalytic networks (2018) · cites this paper as [45]

    The Introduction discusses a large diversity of abiotic organic compounds, but does not estimate amphiphile diversity at life’s origin. The Conclusion and outlook says lipids remain a compound class to be explored. Searches for amphiphiles, a million species, and vesicles found no passage supporting the cited estimate of NG = 10^6. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 60 · Cited by 26

Research works printed but not linked: 51

  1. [1]Lewis GN 1916 The atom and the molecule. J. Am. Chem. Soc. 38, 762– 785. (10.1021/ja02261a002) · DOI
  2. [2]Blum LC, Reymond J-L 2009 970 Million druglike small molecules for virtual screening in the chemical universe database GDB-13. J. Am. Chem. Soc. 131, 8732– 8733. (10.1021/ja902302h) 19505099 · DOI
  3. [3]Polishchuk P, Madzhidov T, Varnek A 2013 Estimation of the size of drug-like chemical space based on GDB-17 data. J. Comput. Aided Mol. Des 27, 675– 679. (10.1007/s10822-013-9672-4) 23963658 · DOI · Paper page
  4. [4]Kirkpatrick P, Ellis C 2004 Chemical space. Nature 432, 823 (10.1038/432823a) · DOI
  5. [5]Gorse A-D 2006 Diversity in medicinal chemistry space. Curr. Top. Med. Chem. 6, 3– 18. (10.2174/156802606775193310) 16454754 · DOI
  6. [8]Meringer M, Cleaves HJ, Freeland SJ 2013 Beyond terrestrial biology: charting the chemical universe of α-amino acid structures. J. Chem. Inf. Model. 53, 2851– 2862. (10.1021/ci400209n) 24152173 · DOI
  7. [9]Cleaves HJ, Meringer M, Goodwin J 2015 227 Views of RNA: is RNA unique in its chemical isomer space? Astrobiology 15, 538– 558. (10.1089/ast.2014.1213) 26200431 PMC4523004 · DOI
  8. [10]Lindsay RK, Buchanan BG, Feigenbaum EA, Lederberg J 1980 Applications of artificial intelligence for organic chemistry: the DENDRAL project. New York, NY: McGraw–Hill.
  9. [12]Read RC 1978 Everyone a winner or how to avoid isomorphism search when cataloguing combinatorial configurations. Ann. Discrete Math. 2, 107– 120. (10.1016/S0167-5060(08)70325-X) · DOI
  10. [13]Luks EM 1982 Isomorphism of graphs of bounded valence can be tested in polynomial time. J. Comput. Syst. Sci. 25, 42– 65. (10.1016/0022-0000(82)90009-5) · DOI
  11. [14]Kerber A, Laue R, Moser D 1990 Ein Strukturgenerator für molekulare Graphen. Anal. Chim. Acta 235, 221– 228. (10.1016/S0003-2670(00)82078-4) · DOI
  12. [15]Ilardo M, Meringer M, Freeland S, Rasulev B, Cleaves HJ II 2015 Extraordinarily adaptive properties of the genetically encoded amino acids. Sci. Rep. 5, 1 (10.1038/srep09414) PMC4371090 25802223 · DOI
  13. [16]Kwok S 2016 Complex organics in space from solar system to distant galaxies. Astron. Astrophys. Rev. 24, 733 (10.1007/s00159-016-0093-y) · DOI
  14. [17]Caselli P, Ceccarelli C 2012 Our astrochemical heritage. Astron. Astrophys. Rev. 20, 151 (10.1007/s00159-012-0056-x) · DOI
  15. [19]Pizzarello S, Shock E 2010 The organic composition of carbonaceous meteorites: the evolutionary story ahead of biochemistry. Cold Spring Harb. Perspect. Biol. 2, a002105 (10.1101/cshperspect.a002105) 20300213 PMC2829962 · DOI · Paper page
  16. [21]Wollrab E, Scherer S, Aubriet F, Carré V, Carlomagno T, Codutti L, Ott A 2016 Chemical analysis of a ‘Miller-type’ complex prebiotic broth. Orig. Life Evol. Biosph. 46, 149– 169. (10.1007/s11084-015-9468-8) 26508401 · DOI · Paper page
  17. [22]Vuitton V et al. 2010 Very high resolution mass spectrometry of HCN polymers and tholins. Faraday Discuss. 147, 495– 508. (10.1039/c003758c) 21302562 · DOI
  18. [23]McGuigan M, Waite JH, Imanaka H, Sacks RD 2006 Analysis of Titan tholin pyrolysis products by comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry. J. Chromatogr. A 1132, 280– 288. (10.1016/j.chroma.2006.07.069) 16934276 · DOI
  19. [24]Ji HF, Li XJ, Zhang HY 2009 Natural products and drug discovery. EMBO Rep. 10, 194– 200. (10.1038/embor.2009.12) 19229284 PMC2658564 · DOI
  20. [25]Dobson CM 2004 Chemical space and biology. Nature 432, 824– 828. (10.1038/nature03192) 15602547 · DOI
  21. [26]Goto S, Okuno Y, Hattori M, Nishioka T, Kanehisa M 2002 LIGAND: database of chemical compounds and reactions in biological pathways. Nucleic Acids Res. 30, 402– 404. (10.1093/nar/30.1.402) 11752349 PMC99090 · DOI
  22. [27]Cleaves HJ 2012 Prebiotic chemistry: what we know, what we don't. Evol. Educ. Outreach 5, 342– 360. (10.1007/s12052-012-0443-9) · DOI · Paper page
  23. [29]Brown AC 1864 XLIV.—On the theory of isomeric compounds. Trans. R. Soc. Edinburgh. 23, 707– 719. (10.1017/S0080456800020007) · DOI
  24. [30]Sylvester JJ 1878 Chemistry and algebra. Nature 17, 284 (10.1038/017284a0) · DOI
  25. [31]Balaban AT 1991 Enumeration of isomers. In Chemical graph theory introduction and fundamentals (eds Bunched D, Rouvray DH), pp. 177– 234. New York, NY: Abacus Press – Gordon and Breach.
  26. [32]McNaught AD, Wilkinson A 1997 Compendium of chemical terminology: IUPAC recommendations. Oxford, UK: Blackwell Science.
  27. [33]Kerber A, Laue R, Meringer M, Rücker C, Schymanski E 2014 Mathematical chemistry and chemoinformatics: structure generation, elucidation and quantitative structure-property relationships. Berlin, Germany: De Gruyter.
  28. [34]Trinajstic N 1992 Chemical graph theory, 2nd edn Boca Raton, FL: CRC Press.
  29. [35]Bonchev D 1991 Chemical graph theory: introduction and fundamentals. London, UK: Taylor & Francis.
  30. [36]Todeschini R, Consonni V, Mannhold R, Kubinyi H, Timmerman H. 2008 Handbook of molecular descriptors. New York, NY: Wiley.
  31. [37]Dehmer M, Varmuza K, Bonchev D, Emmert-Streib F. 2012 Statistical modelling of molecular descriptors in QSAR/QSPR. New York, NY: Wiley.
  32. [38]Gasteiger J, Engel T. 2006 Chemoinformatics. New York, NY: Wiley.
  33. [39]Fink T, Reymond J-L 2007 Virtual exploration of the chemical universe up to 11 atoms of C, N, O, F: assembly of 26.4 million structures (110.9 million stereoisomers) and analysis for new ring systems, stereochemistry, physicochemical properties, compound classes, and drug discovery. J. Chem. Inf. Model. 47, 342– 353. (10.1021/ci600423u) 17260980 · DOI
  34. [40]Ruddigkeit L, Van Deursen R, Blum LC, Reymond J-L 2012 Enumeration of 166 billion organic small molecules in the chemical universe database GDB-17. J. Chem. Inf. Model. 52, 2864– 2875. (10.1021/ci300415d) 23088335 · DOI · Paper page
  35. [41]Kerber A, Laue R, Meringer M, Rücker C 2007 Molecules in silico: a graph description of chemical reactions. J. Chem. Inf. Model. 47, 805– 817. (10.1021/ci600470q) 17532665 · DOI
  36. [42]Dugundji J, Ugi I 1973 An algebraic model of constitutional chemistry as a basis for chemical computer programs. In Computers in chemistry, pp. 19– 64. Berlin, Germany: Springer.
  37. [43]Temkin ON, Zeigarnik AV, Bonchev DG 1996 Chemical reaction networks: a graph-theoretical approach. London, UK: Taylor & Francis.
  38. [44]Benko G, Flamm C, Stadler PF 2003 Graph-based toy model of chemistry. J. Chem. Inf. Comput. Sci. 43, 1085– 1093. (10.1021/ci0200570) 12870897 · DOI
  39. [46]Andersen JL, Flamm C, Merkle D, Stadler PF 2015 In silico support for Eschenmoser's glyoxylate scenario. Isr. J. Chem. 55, 919– 933. (10.1002/ijch.201400187) · DOI
  40. [48]Meringer M. 2010 Structure enumeration and sampling. In Handbook of chemoinformatics algorithms, pp. 233– 267. Boca Raton, FL: CRC/Chapman & Hall.
  41. [49]Gugisch R et al 2016 MOLGEN 5.0, a molecular structure generator. In Advances in mathematical chemistry and applications, revised edn (eds SC Bashak, G Restrepo, JL Villaveces), pp. 113– 138. Amsterdam, The Netherlands: Elsevier.
  42. [50]Philip GK, Freeland SJ 2011 Did evolution select a nonrandom ‘alphabet’ of amino acids? Astrobiology 11, 235– 240. (10.1089/ast.2010.0567) 21434765 · DOI
  43. [51]Wong JT, Bronskill PM 1979 Inadequacy of prebiotic synthesis as origin of proteinous amino acids. J. Mol. Evol. 13, 115– 125. (10.1007/BF01732867) 480369 · DOI
  44. [52]Powner MW, Gerland B, Sutherland JD 2009 Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions. Nature 459, 239– 242. (10.1038/nature08013) 19444213 · DOI · Paper page
  45. [53]Sanchez RA, Orgel LE 1970 Studies in prebiotic synthesis. V. Synthesis and photoanomerization of pyrimidine nucleosides. J. Mol. Biol. 47, 531– 543. (10.1016/0022-2836(70)90320-7) 5418170 · DOI · Paper page
  46. [54]Fuller WD, Sanchez RA, Orgel LE 1972 Studies in prebiotic synthesis: VII. Solid-state synthesis of purine nucleosides. J. Mol. Evol. 1, 249– 257. (10.1007/BF01660244) 4681226 · DOI
  47. [56]Cleaves HJ, Bada J 2012 The prebiotic chemistry of alternative nucleic acids. In Genesis—in the beginning (ed. Seckbach J), pp. 934 Berlin, Germany: Springer.
  48. [57]Zhang L, Peritz A, Meggers E 2005 A simple glycol nucleic acid. J. Am. Chem. Soc. 127, 4174– 4175. (10.1021/ja042564z) 15783191 · DOI · Paper page
  49. [58]Schoning K, Scholz P, Guntha S, Wu X, Krishnamurthy R, Eschenmoser A 2000 Chemical etiology of nucleic acid structure: the alpha-threofuranosyl-(3'–>2') oligonucleotide system. Science 290, 1347– 1351. (10.1126/science.290.5495.1347) 11082060 · DOI · Paper page
  50. [59]Egholm M, Buchardt O, Nielsen PE, Berg RH 1992 Peptide nucleic acids (PNA). Oligonucleotide analogs with an achiral peptide backbone. J. Am. Chem. Soc. 114, 1895– 1897. (10.1021/ja00031a062) · DOI
  51. [60]Meringer M, Cleaves HJ II In press. Computational exploration of the chemical structure space of possible reverse tricarboxylic acid cycle constituents. Sci. Rep. PMC5727506 29235498

Authors
Meringer, M., & Cleaves, H. J.
Affiliations
  • Deutsches Zentrum für Luft- und Raumfahrt e. V. (DLR) (DE)
  • Tokyo Institute of Technology (JP)
Corresponding author
Cleaves, H. James
ORCID
Venue
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences
Publisher
The Royal Society
Published
2017-11-13
Volume
375
Issue
2109
Pages
20160344
ISSN
  • 1364-503X (ISSN-L)
  • 1471-2962
DOI
10.1098/rsta.2016.0344
PMC
PMC5686402
OpenAlex
W2767444775
Cited by
26
References
60
Citations by year
2026: 1 · 2025: 1 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 5 · 2019: 6 · 2018: 3 · 2017: 1
FWCI
2.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Philosophical Transactions of the Royal Society A Mathematical Physical and Engineering Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • elib (German Aerospace Center) (acceptedVersion)
Funders
  • Earth-Life Science Institute (JSPS KAKENHI)
  • ELSI Origins Network (John Templeton Foundation)
Topics
  • Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
  • Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Space Science and Extraterrestrial Life
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
origin of life, astrobiology, chemical space, abiotic synthesis, organic compounds, self-organization, prebiotic chemistry
MeSH terms
Origin of Life, Amino Acids, Computer Simulation, Exobiology, Life

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review