Neighbor effect on conformational spaces of alanine residue in azapeptides
Ho-Jin Lee,
Shi-Wei Liu,
Máté Sulyok-Eiler,
Veronika Harmat,
Viktor Farkas,
Zoltán Bánóczi,
Mouna El Khabchi,
Hua-Jun Shawn Fan,
Kimihiko Hirao,
Jong-Won Song
Affiliations
Ho-Jin Lee
Division of Natural and Mathematics Sciences, LeMoyne-Own College, Memphis, TN, 38126, USA; Department of Natural Sciences, Southwest Tennessee Community College, Memphis, TN, 38015, USA; Corresponding author. Division of Natural and Mathematics Sciences, LeMoyne-Own College, Memphis, TN, 38126, USA.
Shi-Wei Liu
College of Chemical Engineering, Sichuan University of Science and Engineering, Zigong City, Sichuan Province, 64300, PR China
Máté Sulyok-Eiler
Laboratory of Structural Biology and Chemistry, Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary; Hevesy György PhD School of Chemistry, Eötvös Loránd University, Budapest, Hungary
Veronika Harmat
Laboratory of Structural Biology and Chemistry, Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary; HUN-REN - ELTE Protein Modeling Research Group, Budapest, Hungary
Viktor Farkas
Laboratory of Structural Biology and Chemistry, Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary; HUN-REN - ELTE Protein Modeling Research Group, Budapest, Hungary
Zoltán Bánóczi
Department of Organic Chemistry, Institute of Chemistry, ELTE Eötvös Loránd University, 1117, Budapest, Hungary; HUN-REN-ELTE Research Group of Peptide Chemistry, 1117, Budapest, Hungary; Corresponding author. Department of Organic Chemistry, Institute of Chemistry, ELTE Eötvös Loránd University, 1117, Budapest, Hungary.
Mouna El Khabchi
LIMAS, Faculty of Sciences Dhar El Mahraz, University Sidi Mohamed Ben Abdallah, Fez, Morocco
Hua-Jun Shawn Fan
College of Chemical Engineering, Sichuan University of Science and Engineering, Zigong City, Sichuan Province, 64300, PR China; Corresponding author. College of Chemical Engineering, Sichuan University of Science and Engineering, Zigong City, Sichuan Province, 64300, PR China.
Kimihiko Hirao
Fukui Institute for Fundamental Chemistry, Kyoto University, Takano, Nishihiraki-cho 34-4, Sakyo-ku, Kyoto, 606-8103, Japan
Jong-Won Song
Department of Chemistry Education, Daegu University, Daegudae-ro 201, Gyeongsan-si, Gyeongsangbuk-do, 38453, Republic of Korea
The conformational properties of Alanine (Ala) residue have been investigated to understand protein folding and develop force fields. In this work, we examined the neighbor effect on the conformational spaces of Ala residue using model azapeptides, Ac-Ala-azaGly-NHMe (3, AaG), and Ac-azaGly-Ala-NHMe (4, aGA1). Ramachandran energy maps were generated by scanning (φ, ψ) dihedral angles of the Ala residues in models with the fixed dihedral angles (φ = ±90°, ψ = ±0° or ±180°) of azaGly residue using LCgau-BOP and LCgau-BOP + LRD functionals in the gas and water phases. The integral-equation-formalism polarizable continuum model (IEF-PCM) and a solvation model density (SMD) were employed to mimic the solvation effect. The most favorable conformation of Ala residue in azapeptide models is found as the polyproline II (βP), inverse γ-turn (γ′), β-sheet (βS), right-handed helix (αR), or left-handed helix (αL) depending on the conformation of neighbor azaGly residue in isolated form. Solvation methods exhibit that the Ala residue favors the βP, δR, and αR conformations regardless of its position in azapeptides 3 and 4 in water. Azapeptide 5, Ac-azaGly-Ala-NH2 (aGA2), was synthesized to evaluate the theoretical results. The X-ray structure showed that azaGly residue adopts the polyproline II (βP) and Ala residue adopts the right-handed helical (αR) structure in aGA2. The conformational preferences of aGA2 and the dimer structure of aGA2 based on the X-ray structure were examined to assess the performance of DFT functionals. In addition, the local minima of azapeptide 6, Ac-Phe-azaGly-NH2 (FaG), were compared with the previous experimental results. SMD/LCgau-BOP + LRD methods agreed well with the reported experimental results. The results suggest the importance of weak dispersion interactions, neighbor effect, and solvent influence in the conformational preferences of Ala residue in model azapeptides.
