Computational Data Archive in Support of the Linear and Cyclic Peptide Formation and Hydrolysis Molecular Mechanisms

In search for the goldilocks zone in the chemical space for amino acid oligomerization that is relevant to the emergence of protein-based metabolism, we investigated the formation mechanism of peptide bond in linear and cyclic peptides under hydrothermal conditions in bulk water. For both product formation, we identified a multi-step mechanisms that reproduces the experimentally known barriers. By careful evaluation of a comprehensive set of levels of theory, modelling of solvation effect, and calculation of thermochemical parameters, we established a robust computational model to expand the bulk water focus to interfacial phenomena of atmospheric/hydrospheric and litospheric/hydrospheric boundaries. In both investigations we differentiated among various scenarios that allows for drawing conclusions for peptide condensations in gas phase/vacuum, high-temperature/close to boiling aqueous environments, hydrothermal conditions, and ambient conditions with pH effect. 

The cyclic peptide study also well demonstrate the important role of Nuclear Quantum Effects as determined from multi-component density functional calculations.

While we cannot travel back in time billions of years to witness the "birth" of the first macromolecule with pre-biotic relevance, we present the dataset and the corresponding publication in RSC Organic and Biomolecular Chemistry (July 26, 2023 issue for the linear peptide and TBD 2026 issue for the cyclic peptide) as our efforts to establish an unbiased computational platform, where we can evaluate experiments and generate experimentally testable ideas.