Mechanism and Free-Energy Landscape of Peptide Bond Formation at the Silica–Water Interface

The amino acid condensation reaction on a heterogeneous mineral surface has been regarded as one of the important pathways for peptide bond formation. In this work, the mechanism of peptide bond formation over a silica surface in an aqueous environment is studied using ab initio molecular dynamics calculations coupled with enhanced sampling methods such as metadynamics and umbrella sampling. The model includes a periodically repeated slab of amorphous SiO2 forming an interface with explicit liquid water. The adopted simulation method allowed reconstruction of a prejudice-free reaction mechanism of glycine dimerization and quantification of the corresponding free energy profile, with a detailed characterization of transition states and of the role of water. The resulting three-step mechanism features an overall free energy barrier of 155 kJ/mol at 300 K. In comparison to the bulk liquid phase, our results indicate that the interface has a strong catalytic effect on the condensation reaction, which we trace back to the capability of the silica-water interface in promoting an addition reaction by a transition state stabilization. The silica-water interface is found to behave as a less-polar reaction medium with respect to bulk water, promoting addition reactions and disfavoring elimination reactions.