Computational Study of Driving Forces in ATSP, PDIQ, and P53 Peptide Binding: C=O···C=O Tetrel Bonding Interactions at Work

[Image: see text] Understanding the molecular interactions that drive peptide folding is crucial to chemistry and biology. In this study, we analyzed the role of CO···CO tetrel bonding (TtB) interactions in the folding mechanism of three different peptides (ATSP, pDIQ, and p53), which exhibit a different propensity to fold in an α helix motif. To achieve this goal, we used both a recently developed Bayesian inference approach (MELDxMD) and Quantum Mechanics (QM) calculations at the RI-MP2/def2-TZVP level of theory. These techniques allowed us to study the folding process and to evaluate the strength of the CO···CO TtBs as well as the synergies between TtBs and hydrogen-bonding (HB) interactions. We believe that the results derived from our study will be helpful for those scientists working in computational biology, peptide chemistry, and structural biology.