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Quantum mechanical study of the conformational behavior of proline and 4R‐hydroxyproline dipeptide analogues in vacuum and in aqueous solution
Author(s) -
Benzi Caterina,
Improta Roberto,
Scalmani Giovanni,
Barone Vincenzo
Publication year - 2002
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.10015
Subject(s) - pyrrolidine , chemistry , intramolecular force , dihedral angle , dipeptide , conformational isomerism , hydrogen bond , crystallography , ring (chemistry) , substituent , stereochemistry , computational chemistry , peptide , molecule , organic chemistry , biochemistry
The conformational behavior of the title compounds has been investigated by Hartree–Fock, MP2, and DFT computations on the most significant structures related to variations of the backbone dihedral angles, cis/trans isomerism around the peptide bond, and diastereoisomeric puckering of the pyrrolidine ring. In vacuum the reversed γ turn (γ l ), characterized by an intramolecular hydrogen bridge, corresponds to the absolute energy minimum for both puckerings (up and down) of the pyrrolidine ring. An additional energy minimum is found in the helix region, but only for an up puckering of the pyrrolidine ring. When solvent effects are included by means of the polarizable continuum model the conformer observed experimentally in condensed phases becomes the absolute minimum. The down puckering is always favored over its up counterpart, albeit by different amounts (0.4–0.5 kcal/mol for helical structures and about 2 kcal/mol for γ l structures). In helical structures cis arrangements of the peptide bond are only slightly less stable than their trans counterparts. This is no longer true for γ l structures, because the formation of an intramolecular hydrogen bond is possible only for trans peptide bonds. In most cases, proline and hydroxyproline show the same general trends; however, the electronegative 4(R) substituent of hydroxyproline leads to a strong preference for up puckerings irrespective of the backbone conformation. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 341–350, 2002