biostudies-literatureUnknown28(5)Joshi AIndia Ministry of Science &amp; Technology Department of BiotechnologyProlyl-4-hydroxylation is an ancient evolutionarily conserved post-translational modification (PTM) critical for both structural and regulatory functions in multicellular life forms. This PTM plays a pivotal role in stabilizing collagen's triple helix by influencing the puckering of the pyrrolidine ring. The elegant interplay between ring pucker, torsional angles, peptide bond isomerization, and charge-transfer interactions (O···C=O n→π∗ and σ→σ∗) attaining the helical stability remains underappreciated. Using density functional theory calibrated against gold standard <i>ab initio</i> methods, we analyzed a physiologically relevant collagenous peptide proline-4-hydroxyproline-glycine (PO⁴G) to establish the correlation between stereo-electronic effects due to prolyl-4-hydroxylatiScience112393https://www.ebi.ac.uk/biostudies/studies/S-EPMC12059709biostudies-literatureDecoding elegant interplay among different stereo-electronic effects due to the ancient prolyl-4-hydroxylation stabilizing collagenous helicity.PMC12059709Basak TMondal BJoshi AfalseDecoding elegant interplay among different stereo-electronic effects due to the ancient prolyl-4-hydroxylation stabilizing collagenous helicity.Prolyl-4-hydroxylation is an ancient evolutionarily conserved post-translational modification (PTM) critical for both structural and regulatory functions in multicellular life forms. This PTM plays a pivotal role in stabilizing collagen's triple helix by influencing the puckering of the pyrrolidine ring. The elegant interplay between ring pucker, torsional angles, peptide bond isomerization, and charge-transfer interactions (O···C=O n→π∗ and σ→σ∗) attaining the helical stability remains underappreciated. Using density functional theory calibrated against gold standard <i>ab initio</i> methods, we analyzed a physiologically relevant collagenous peptide proline-4-hydroxyproline-glycine (PO⁴G) to establish the correlation between stereo-electronic effects due to prolyl-4-hydroxylat2025-01-01T00:00:00Z2025 May2026-06-01T05:23:30.378Z2026-04-08T09:36:21.186ZS-EPMC120597094034328110.1016/j.isci.2025.112393