Conformational flexibility of PPII-helix: A density functional theory study

Deciphering the Backbone Noncovalent Interactions that Stabilize Polyproline II Conformation and Reduce cis Proline Abundance in Polyproline Tracts

“…In GPP, GPP-I (gly−endo−endo) was the most stable and GPP-III (gly−exo−exo) was the least stable conformer (Figure 2D). From the relative energies of various conformations of PP, PPP, PPG, and GPP, it is evident that the γ-endo ring pucker of the pyrrolidine ring of Pro is more favored than the γ-exo ring pucker in the PPII conformation, which is in agreement with the previous report of Guo et al 50 An important structural difference that can arise from the γendo ring pucker preference is the relatively larger φ and ψ angles in the γ-endo conformation compared to that of γ-exo (Tables S1−S3,S5,S6, and S8).…”

“…44−49 However, in a recent theoretical study, it was observed that Pro prefers γendo conformation in the PPII conformation of poly-P despite the γ-exo conformation providing a higher stabilization via CO•••CO n O → π* CO interactions, which contradicts the stabilization theory of PPII helices based on CO•••CO interactions. 50 Nonetheless, CO•••CO interactions were also observed in the solid-state structures of the PPII helical polylactic acid (PLA) pentamer, 51,52 the oligo-Pro hexamer, 39 the cis-4,5-methanoproline tetramer, 42 and the Oic-hexamer, 43 which suggest a role of CO•••CO interactions in the stabilization of PPII helices.…”

“…Raines and co-workers explained the stabilization of PPII helices and collagen triple helices by CO···CO n → π* interactions among the adjacent backbone CO groups. ,− They also demonstrated that the CO···CO n → π* interactions were stronger when the pyrrolidine ring of Pro exists in the γ- exo conformation (Figure B–C) by designing hyperstable collagen-mimetic peptides (CMPs) via strategic incorporation of γ- exo Pro residues in the CMP backbone. − However, in a recent theoretical study, it was observed that Pro prefers γ- endo conformation in the PPII conformation of poly-P despite the γ- exo conformation providing a higher stabilization via CO···CO n O → π* CO interactions, which contradicts the stabilization theory of PPII helices based on CO···CO interactions . Nonetheless, CO···CO interactions were also observed in the solid-state structures of the PPII helical polylactic acid (PLA) pentamer, , the oligo-Pro hexamer, the cis -4,5-methanoproline tetramer, and the Oic-hexamer, which suggest a role of CO···CO interactions in the stabilization of PPII helices.…”