Atomistic simulations in prebiotic chemistry – a dialog between experiment and theory
Location : Sorbonne University, Pierre et Marie Curie Campus 4 Place Jussieu, 75005 Paris France
July 1, 2019 – July 3, 2019
The origin of life is among the greatest open problems in science—How is it that life can emerge from non-living matter? An answer is critical for understanding our own origins, for identifying the most promising targets in the search for life in other worlds, and for synthesizing new life in the lab. The beginnings of life on our planet date back approximately 4 billion years. During this time period in Earth’s history, a process of prebiotic chemical evolution was sparked, which gave rise to the emergence of simple biologically active molecules from an inanimate matter.
During the second part of the 19th century, the emergence of Darwin’s evolutionary theory fostered scientific efforts to understand life’s origins on our planet. In 1924, A. I. Oparin, a Soviet biologist, published his primordial soup theory proposing that life originated from simple nonliving organic compounds through gradual chemical evolution. Haldane introduced a similar concept for abiogenesis and their contribution is nowadays known as the Oparin-Haldane Hypothesis. In 1953, Miller and Urey reported (Miller & Urey 1) the surprising results they have achieved by the application of an electric discharge on a mixture of the gases composed of CH4, NH3, H2O, and H2 that simulated what was considered at the time as a model atmosphere for the primordial Earth. The result of this experiment was a substantial yield of a mixture of aminoacids (Lazcano 2). Similarly, Orò demonstrated the spontaneous formation of nucleic acids bases from aqueous hydrogen cyanide subjected to heating (Oro 3). Since then, a number of different hypotheses have been formulated in order to explain the synthesis of the building blocks of the first biological materials from small inorganic and organic precursors as well as how these building blocks could self-assemble to form functional biomolecules. In the last 60 years various prebiotic scenarios have been suggested differing in the type of energy used for the synthesis: e.g. UV irradiation both in extra-terrestrial and terrestrial environments (Munoz 4), hydrothermal energy from deep sea vents (Amend 5), shock waves from meteorite impact (Martins 6), redox energy in the “iron-sulphur world” hypothesis (Huber 7), radioactive emission from uranium accumulation (Parnel 8), mineral geochemistry (Lambert 9) and, of course, electric discharges originated by lightning, which motivated the Miller-Urey experiment. The last couple of years witnessed an unprecedented development in the research of the origin of the first genetic materials. Two main concurrent scenarios have been formulated for the prebiotic synthesis of nucleotides (Saladino 10, Sutherland 11). Moreover, recent experimental papers point to formamide as a prebiotic hub (Ferus 12, Saladino 13). Self-organization of nucleotide precursors leading to RNA-like molecules has also been addressed recently (Maurel 14, Di Mauro&Sponer 15).
Theory and modeling have generally provided considerable insight (Barone 16, Koch 17, Wang 18, Woon 19) into prebiotic chemistry, as developments in computational chemistry methodologies have opened the door to in silico modeling of more and more complex systems. Ab initio molecular dynamics (AIMD) is one of such computational methods, which incorporates quantum chemical calculations and molecular dynamics allowing for the simulation of chemical reactivity at finite temperature and pressure. Significant new insight has been obtained through AIMD studies on the mechanisms and barriers for the synthesis of simple organic molecules on substrates such as ice (Rimola 20) or minerals (Wang 21, Jeilani 22), the simulation of the effect of the pressure/temperature shock waves induced by the impact of bolides in the early Earth (Goldman 23), the recent first in silico Miller-Urey experiment (Saitta&Saija 24), the simulation of peptide synthesis and oligomerization at hydrothermal conditions (Schreiner 25, Pietrucci 38), or the determination of chemical paths leading to the formation of sugars (Cassone 26, Civis 27), nucleosides (Saladino 28, Ferus 41), and nucleotides (Sponer 29, Perez-Villa 39). Photochemistry of life’s origin has been addressed in several theoretical works (Barbatti 30, Szabla 31). Classical MD calculations have been used to unravel how the first RNA molecules could acquire their catalytic function that made possible evolution of the species on the Earth (Stadlbauer 32). A review on “Prebiotic Chemistry and the Origins of Life Research with atomistic computer simulations” by two of the proponents has just been accepted in “Physics of Life: reviews” (Perez-Villa 40).
A newly emerging direction of the modern origin of life research focusses on the non-equilibrium aspects of prebiotic chemistry. Pioneering studies of the Braun group have shown that length-selective accumulation of oligonucleotides can be achieved via thermophoresis in thermal traps, hinting at the fact that accumulation of biopolymers on the early Earth was not necessarily dictated by the rules of equilibrium thermodynamics (Mast 33). Another study has used theoretical tools to demonstrate that formamide, a molecule generally considered to be a highly relevant prebiotic feedstock molecule, could accumulate on the early Earth in the pores of rocks due to thermophoresis and convection (Niether 34). Non-equilibrium chemistry forms the basis of a recently formulated formamide-based origin model, in which the stepwise decrease of the temperature of the environment drives those complex chemical transformations that could lead to the emergence of more and more complex molecules from the prebiotic pool (Sponer 35). The importance of non-equilibrium chemistry in the evolution of droplet protocells (Parrilla-Gutierrez 36) or in the bistable behavior of non-enzymatic self-replication networks (Wagner 37) has been demonstrated by recent studies.
However, if the potential benefit of computer simulations in the study of atomic processes at conditions hard or even impossible to reach experimentally is clear, huge challenges remain to be tackled because of the chemical complexity of the systems and the many different time and length scales involved, as well as due to the many possible scenarios.
 Miller SL, Urey HC. Organic compound synthesis on the primitive Earth. Science 130, 245–251 (1959).
 Lazcano A, Bada JL. The 1953 Stanley L. Miller experiment: Fifty years of prebiotic organic chemistry. Orig Life Evol Biosph 33, 235–242 (2003).
 Oro J. Mechanism of synthesis of adenine from hydrogen cyanide under possible primitive Earth conditions. Nature 191, 1193–1194 (1961).
 Munoz Caro GMM et al. Amino acids from ultraviolet irradiation of interstellar ice analogues. Nature 416, 403–406 (2002).
 Amend JP, Shock EL (1998) Energetics of amino acid synthesis in hydrothermal ecosystems. Science 281, 1659–1662 (1998).
 Martins Z, Price MC, Goldman N, Sephton MA, Burchell MJ Shock synthesis of amino acids from impacting cometary and icy planet surface analogues. Nat Geosci 6, 1045–1049 (2013).
 Huber C, Wächtershäuser G. Peptides by activation of amino acids with CO on (Ni,Fe)S surfaces: Implications for the origin of life. Science 281, 670–672. (1998).
 Parnell J. Mineral radioactivity in sands as a mechanism for fixation of organic carbon on the early Earth. Orig Life Evol Biosph 34, 533–547 (2004).
 Lambert JF, Adsorption and Polymerization of Amino Acids on Mineral Surfaces: A Review. Orig. Life Evol. Biosph. 38, 211–242 (2008).
 Saladino R, Botta G, Pino S, Costanzo G, Di Mauro E. Genetics first or metabolism first? The formamide clue. Chem Soc Rev 41, 5526–5565 (2012).
 Powner MW, Gerland B, Sutherland JD Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions. Nature, 459, 239-242 (2009).
 Ferus, M, Nesvorn, D, Sponer, J, Kubelk, P, Michalckov, R, Shestivsk, V, Sponer, J. E, & Civis, S. High-energy chemistry of formamide: A unified mechanism of nucleobase formation. Proceedings of the National Academy of Sciences 112, 657–662 (2015).
 Saladino, R, Carota, E, Botta, G, Kapralov, M, Timoshenko, G. N, Rozanov, A. Y,
Krasavin, E, & Di Mauro, E. Meteorite-catalyzed syntheses of nucleosides and of other prebiotic compounds from formamide under proton irradiation. Proceedings of the National Academy of Sciences 112, E2746–E2755 (2015).
 Da Silva L, Maurel M-C, Deamer D. Salt-Promoted Synthesis of RNA-like Molecules in Simulated Hydrothermal Conditions. J. Mol. Evol., 80, 86-97 (2015).
 Šponer JE, Šponer J, Giorgi A, Di Mauro E, Pino S, Costanzo G. Untemplated Nonenzymatic Polymerization of 3′,5′cGMP: A Plausible Route to 3′,5′-Linked Oligonucleotides in Primordia. J. Phys. Chem. B, 119, 2979-2989 (2015).
 Barone V, Biczysko M, Puzzarini C. Quantum chemistry meets spectroscopy for astrochemistry: increasing complexity toward prebiotic molecules, Acc. Chem. Res. 48, 1413-1422 (2015).
 Koch DM, Toubin C, Peslherbe GH, Hynes JT. A Theoretical Study of the Formation of the Aminoacetonitrile Precursor of Glycine on Icy Grain Mantles in the Interstellar Medium. J. Phys. Chem. C 112, 2972-2980 (2008).
 Wang J, Gu J, Nguyen MT, Springsteen G, Leszczynski J. From formamide to purine: An energetically viable mechanistic reaction pathway. J Phys Chem B 117, 2314–2320 (2013).
 Woon DE. A quantum chemical study of the formation of cyanide (CN-) and acetate (CH3COO-) ions in astrophysical ices via proton transfer from HCN, HNC, or CH3COOH to NH3. Comp. Theor. Chem. 984, 108-112 (2012).
 Rimola A, Sodupe M, Ugliengo P. Deep-space glycine formation via Strecker-type reactions activated by ice water dust mantles. A computational approach. PCCP 12, 5285-5294 (2010).
 Wang LP, Titov A, McGibbon R, Liu F, Pande VS, Martinez TJ. Discovering chemistry with an ab initio nanoreactor. Nature Chemistry 7, 323-327 (2015).
 Jeilani YA, Nguyen HT, Newallo D, Dimandja JMD, Nguyen MT. Free radical routes for prebiotic formation of DNA nucleobases from formamide, PCCP 15, 21084-21093 (2013).
 Goldman N, Reed EJ, Laurence EF, William Kuo, L-F, Maiti A. Synthesis of glycine-containing complexes in impacts of comets on early Earth, Nature Chemistry 2, 949-954 (2010).
 Saitta AM, Saija F. Miller experiments in atomistic computer simulation. PNAS 111, 13769-13773 (2014).
 Schreiner E, Nair NN, Wittekindt C, Marx D, Peptide Synthesis in Aqueous Environments: The Role of Extreme Conditions and Pyrite Mineral Surfaces on Formation and Hydrolysis of Peptides, J. Am. Chem. Soc. 133, 8216–8226 (2011).
 Cassone G, Šponer J, Šponer JE, Pietrucci F, Saitta AM, Saija F. Chem. Commun., 54, 3211-3214 (2018).
 Civiš S, Szabla R, Szyja BM, Smykowski D, Ivanek O, Knížek A, Kubelík P, Šponer J, Ferus M, Šponer JE. Sci. Rep. 6, 23199 (2016).
 Saladino R, Bizzarri BM, Botta L, Šponer J, Šponer JE, Georgelin T, Jaber M, Rigaud B, Kapralov M, Timoshenko GN, Rozanov A, Krasavin E, Timperio AM, Di Mauro E. Sci. Rep. 7, 14709 (2017).
 Šponer JE, Šponer J, Fuentes-Cabrera M. Chem. Eur. J. 17, 847-854 (2011).
 Boulanger E, Anakuthil A, Nachtigallova D, Thiel W, Barbatti M. Photochemical Steps in Prebiotic Synthesis of Purine Precursors from HCN, Angew. Chem. Int. Ed. 52, 8000-8003 (2003).
 Szabla R., Campos J, Sponer JE, Sponer J, Gora RW, Sutherland JD. Excited-state hydrogen atom abstraction initiates the photochemistry of b-20-deoxycytidine Chem. Sci. 6, 2035-2043 (2015).
 Stadlbauer P, Šponer J, Costanzo G, Di Mauro E, Pino S, Šponer JE. Tetraloop-like geometries could form the basis of the catalytic activity of the most ancient ribooligonucleotides. Chem. Eur. J. 21, 3596-3604 (2015).
 Mast CB, Schink S, Gerland U, Braun D. Proceedings of the National Academy of Sciences of the United States of America 110, 8030-8035 (2013).
 Niether D, Afanasenkau D, Dhont JKG, Wiegand S. Proceedings of the National Academy of Sciences of the United States of America 113, 4272-4277 (2016).
 Šponer JE, Šponer J, Nováková O, Brabec V, Šedo O, Zdráhal Z, Costanzo G, Pino S, Saladino R, Di Mauro E. Chem. Eur. J. 22, 3572-3586 (2016).
 Parrilla-Gutierrez JM, Tsuda S, Grizou J, Taylor J, Henson A, Cronin L. Nat. Commun. 8, 1144 (2017).
 Wagner N, Mukherjee R, Maity I, Peacock-Lopez E, Ashkenasy G. ChemPhysChem 18, 1842-1850 (2017).
 Pietrucci F, Aponte JC, Starr R, Perez-Villa A, Elsila JE, Dowrkin JP, Saitta AM, ACS Earth Space Chem 2, 588 (2018).
 Perez-Villa A et al, ChemRxiv doi:10.26434/chemrxiv.5519041.v4 (2018).
 Perez-Villa A, Pietrucci F, Saitta AM, Physics of Life: Reviews, to appear (2018).
 Ferus M, Pietrucci F, Saitta AM, et at, PNAS 114, 4306-11 (2017).
Frank De Proft (invited speaker) (Vrije Universiteit Brussel (Belgium))
Nathalie Carrasco (invited speaker) (LATMOS, Université Versailles Saint Quentin)
Hervé Cottin (invited speaker) (LISA, Université Paris Est)
Jean-François Lambert (invited speaker) (UPMC)
Uwe Meierhenrich (invited speaker) (Université Cote d”Azur)
Cornelia Meinert (invited speaker) (Université de Nice)
Riccardo Spezia (invited speaker) (CNRS Sorbonne Université)
Simone Wiegand (invited speaker) (Forschungszentrum Jülich)
Nadia Balucani (invited speaker) (DCBB – University of Perugia)
Ernesto Di Mauro (invited speaker) (Università La Sapienza)
Cristina Puzzarini (invited speaker) (Universita’ di Bologna, Dipartimento di Chimica “Giacomo Ciamician”)
Raffaele Saladino (invited speaker) (Università della Tuscia)
Piero Ugliengo (invited speaker) (University of Torino)
Antonio Lazcano Araujo (invited speaker) (Universidad Autonoma Mexico)
Matthew Powner (invited speaker) (University College London)
Nir Goldman (invited speaker) (Lawrence Livermore National La.)
Ram Krishnamurthy (invited speaker) (Scripps Institute UC San Diego)