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.