Discovery of New\nSynthetic Routes of Amino Acids in\nPrebiotic Chemistry

The origin of life on Earth remains one of the most perplexing\nchallenges in biochemistry. While numerous bottom-up experiments under\nprebiotic conditions have provided valuable insights into the spontaneous\nchemical genesis of life, there remains a significant gap in the theoretical\nunderstanding of the complex reaction processes involved. In this\nstudy, we propose a novel approach using a roto-translationally invariant\npotential (RTIP) formulated with pristine Cartesian coordinates to\nfacilitate the simulation of chemical reactions. By employing RTIP\npathway sampling to explore the reactivity of primitive molecules,\nwe identified several low-energy reaction mechanisms, such as two-hydrogen-transfer\nhydrogenation and HCOOH-catalyzed hydration and amination. This led\nto the construction of a comprehensive reaction network, illustrating\nthe synthesis pathways for glycine, serine, and alanine. Further thermodynamic\nanalysis highlights the pivotal role of formaldimine as a key precursor\nin amino acid synthesis, owing to its more favorable reactivity in\ncoupling reactions compared to the traditionally recognized hydrogen\ncyanide. Our study demonstrates that the RTIP methodology, coupled\nwith a divide-and-conquer strategy, provides new insights into the\nsimulation of complex reaction processes, offering promising applications\nfor advancing organic design and synthesis.