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