Conformational preferences of X-Pro sequences: Ala-Pro and Aib-Pro motifs.
Conformational preferences and prolyl cis-trans isomerizations of the X-Pro motifs (Ac-X-Pro-NHMe, X = Ala and Aib) are explored using the meta-hybrid functional M06-2X and the double-hybrid functional B2PLYP-D with empirical dispersion corrections in the gas phase and in water, where solvation free energies were calculated using the implicit SMD model. Ac-Ala-Pro-NHMe favors the type VI β-turns in the gas phase and the open conformations in water. The populations of type VI β-turns decrease from 71% in the gas phase to 21% in water, which is reasonably consistent with IR and NMR experimental results on tBoc-Ala-Pro-NHMe. However, Ac-Aib-Pro-NHMe prefers the type I β-turns with α-helical structures for both residues in the gas phase and in water, whose populations are estimated to be 66% in both phases. These calculated results may rationalize why most of the peptaibiotics containing the Aib-Pro sequence have a regular α-helical conformation at the N- or C-terminus but a kinked α-helical structure in the middle of the helix. The cis-trans isomerizations of the Ala-Pro and Aib-Pro peptide bonds proceed via the clockwise rotation with the different backbone conformations. The rotational barriers to cis-to-trans isomerization are estimated to be 19.73 kcal/mol for the Ala-Pro tripeptide and 16.64 kcal/mol for the Aib-Pro tripeptide in water, which indicates that the rotational barrier becomes lower by ~3 kcal/mol for the Aib-Pro peptide bond. The calculated rotational barrier for Ac-Ala-Pro-NHMe is consistent with the observed value of 19.3 kcal/mol for Suc-Ala-Ala-Pro-Phe-pNA from NMR experiments in a buffered solution.
Byun
Byung Jin
BJ
Department of Chemistry, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Song
Il Keun
IK
Chung
Yong Je
YJ
Ryu
Keun Ho
KH
Kang
Young Kee
YK
D020816:Amino Acid Motifs; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry*; D005740:Gases / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D011789:Quantum Theory; D013237:Stereoisomerism; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D004151:Dipeptides; D005740:Gases; C552620:alpha-aminoisobutyric acid-D-proline; D014867:Water; C038123:alanylproline