title: Conformational Preferences in Small Peptide Models: The Relevance of cis/trans-Conformations.
abstract: The accurate description of cis/trans peptide structures is of fundamental relevance for the field of protein modeling and protein structure determination. A comprehensive conformational analysis of dipeptide model Ace-Gly-NMe (1) has been carried out by using a combination of theoretical calculations and experimental ((1) H and (13) C NMR and NOESY) spectroscopic measurements to assess the relevance of cis-peptide conformers. NMR measurements in dimethyl sulfoxide (DMSO) solution and calculations employing a continuum solvation model both point to the extended trans,trans conformer C5_tt as the global minimum. The cis-peptide structures C5_ct and C5_tc, with the N- or C-terminal amide group in cis-conformation, are observed separately and located 13.0±2 kJ mol(-1) higher in energy. This is in close agreement with the theoretical prediction of around 12 kJ mol(-1) in DMSO. The ability of common protein force fields to reproduce the energies of the cis-amide conformers C5_ct and C5_tc in 1 is limited, making these methods unsuitable for the description of cis-peptide structures in protein simulations.
authors.affiliation: Department of Chemistry, LMU München, Butenandstrasse 5-14, 81377, München, Germany.
authors.forename: Harish
authors.initials: H
authors.lastname: Jangra
authors.affiliation: Institut für Organische Chemie, Universität Regensburg, 93053, Regensburg, Germany.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Haindl
authors.affiliation: Department of Chemistry, LMU München, Butenandstrasse 5-14, 81377, München, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Achrainer
authors.affiliation: Institut für Organische Chemie, Universität Regensburg, 93053, Regensburg, Germany.
authors.forename: Johnny
authors.initials: J
authors.lastname: Hioe
authors.affiliation: Institut für Organische Chemie, Universität Regensburg, 93053, Regensburg, Germany. ruth.gschwind@ur.de.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Gschwind
authors.affiliation: Department of Chemistry, LMU München, Butenandstrasse 5-14, 81377, München, Germany. zipse@cup.uni-muenchen.de.
authors.forename: Hendrik
authors.identifier: http://orcid.org/0000-0002-0534-3585
authors.initials: H
authors.lastname: Zipse
mesh_terms: D003198:Computer Simulation; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004151:Dipeptides / Q000737:chemistry*; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D004151:Dipeptides; D004121:Dimethyl Sulfoxide
keywords: conformation analysis; density functional calculations; peptides; protein folding; protein structures