Improved treatment of cyclic ?-amino acids and successful prediction of ?-peptide secondary structure using a modified force field: AMBER*C

Christianson, Laurie A.; Lucero, Melissa J.; Appella, Daniel H.; Klein, Daniel A.; Gellman, Samuel H.

doi:10.1002/(sici)1096-987x(20000715)21:9<763::aid-jcc5>3.0.co;2-c

Cited by 32 publications

(31 citation statements)

References 66 publications

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“…Conformational profiles of the cyclic peptides were investigated by Macromodel's LLMOD procedure of Kolossváry (58,66–68) using the energy minimization parameters as described above. A total of 10 000 search steps were performed and the conformations with energy difference of 50 kJ/mol from the global minimum were saved.…”

Section: Computational Proceduresmentioning

confidence: 99%

Biological and conformational study of β‐substituted prolines in MT‐II template: steric effects leading to human MC5 receptor selectivity*

Cai

Mayorov

et al. 2004

The Journal of Peptide Research

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To investigate the molecular basis for the interaction of the chi-constrained conformation of melanotropin peptide with the human melanocortin receptors, a series of beta-substituted proline analogs were synthesized and incorporated into the Ac-Nle-C[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 (MT-II) template at the His6 and D-Phe7 positions. It was found that the binding affinities generally diminished as the steric bulk of the p-substituents of the 3-phenylproline residues increased. From (2S, 3R)-3-phenyl-Pro6 to (2S, 3R)-3-(p-methoxyphenyl)-Pro6 analogs the binding affinity decreased 23-fold at the human melanocortin-3 receptor (hMC3R), 17-fold at the hMC4R, and eight-fold at the hMC5R, but selectivity for the hMC5R increased. In addition, the substitution of the D-Phe7 residue with a (2R, 3S)-3-phenyl-Pro resulted in greatly reduced binding affinity (10(3)-10(5)) at these melanocortin receptors. Macromodel's Large Scale Low Mode (LLMOD) with OPLS-AA force field simulations revealed that both MT-II and SHU-9119 share a similar backbone conformation and topography with the exception of the orientation of the side chains of D-Phe7/D-Nal (2')7 in chi space. Introduction of the dihedrally constrained phenylproline analogs into the His6 position (analogs 2-6) caused topographical changes that might be responsible for the lower binding affinities. Our findings indicate that hMC3 and hMC4 receptors are more sensitive to steric effects and conformational constraints than the hMC5 receptor. This is the first example for melanocortin receptor selectivity where the propensity of steric interactions in chi space of beta-modified Pro6 analogs of MT-II has been shown to play a critical role for binding as well as bioefficacy of melanotropins at hMC3 and hMC4 receptors, but not at the hMC5 receptor.

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Section: Computational Proceduresmentioning

confidence: 99%

Biological and conformational study of β‐substituted prolines in MT‐II template: steric effects leading to human MC5 receptor selectivity*

Cai

Mayorov

et al. 2004

The Journal of Peptide Research

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“…It was found that simulations are quite sensitive to the inclusion of long-range electrostatic interactions [18] [19]. Christianson et al also studied the folding process of b-peptides made of trans-2-aminocyclopentanecarboxylic acid and trans-2-aminocyclohexane carboxylic acid derivatives by using a modified AMBER force field [20].…”

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confidence: 99%

Theoretical Study of -Peptide Models: Intrinsic Preferences of Helical Structures

Lin

Zhao

2002

HCA

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Dedicated to Professor Dieter Seebach on the occasion of his 65th birthday b-Peptides form various secondary structures, such as 14-helix, 12-helix, 10/12-helix, 10-helix, 2 8 -ribbon, C6-ribbon, and pleated-sheet. Thus, it is useful to understand the intrinsic backbone conformational preferences of these basic structures. By using a simple repeating-unit method, we have calculated the preferences of C6-ribbon, b-strand, 10/12-helix, 14-helix, 12-helix, 10-helix, and 2 8 -ribbon of a series of poly-b-alanine models, Ac-(b-Ala) n -NH 2 , with n 1 ± 9. Interactions among single amino acids result in cooperative residue energies. This is not found for the formations of b-strands, 2 8 -ribbons, and C6-ribbons, which possess constant residue energies. In contrast, the 12-helix, 10-helix, and 14-helix are characterized by increasing residue energies as the peptide elongates. Therefore, there is a considerable positive cooperative impetus in the gas phase for their formation. The residue energy of the 10/12-helix increases significantly for n 2 and 3, and then displays a zigzag pattern. Meanwhile, there is a good correlation between calculated residue energies and residue dipole moments, indicating the importance of long-range electrostatic interactions to the cooperative residue energy. Efforts have been made to separate the electrostatic and torsional interactions between residues. Thereby, the 12-, 10-, and 10/12-helices all benefit from electrostatic interactions, while the 14-helix has the most intrinsic preference in terms of torsional interaction. The effect of MeOH on the secondary structures has also been evaluated by SCIPCM solvent model calculations.

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“…are possible. Qualitative comparison of the amide A region of the IR spectra in CH 2 Cl 2 of the N ‐isobutyryl methylamide derivatives of trans ‐Achc and trans ‐Acpc indicated that the trans ‐Acpc derivative is more prone to C 8 IHB formation than the trans ‐Achc derivative21. The NH stretching contribution to the amide A band of the C 8 H‐bonded derivatives of trans ‐Achc and trans ‐Acpc appears at 3357 and 3306 cm −1 , respectively, suggesting that the CO and HN in the trans ‐Achc model are not oriented as favorable for a strong hydrogen bond as in the trans ‐Acpc derivative.…”

Section: Introductionmentioning

confidence: 99%

VCD studies on cyclic peptides assembled from L‐α‐amino acids and a trans‐2‐aminocyclopentane‐ or trans‐2‐aminocyclohexane carboxylic acid

Vass

Strijowski

Wollschläger

et al. 2010

Journal of Peptide Science

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The increasing interest in peptidomimetics of biological relevance prompted us to synthesize a series of cyclic peptides comprising trans‐2‐aminocyclohexane carboxylic acid (Achc) or trans‐2‐aminocyclopentane carboxylic acid (Acpc). NMR experiments in combination with MD calculations were performed to investigate the three‐dimensional structure of the cyclic peptides. These data were compared to the conformational information obtained by electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectroscopy. Experimental VCD spectra were compared to theoretical VCD spectra computed quantum chemically at B3LYP/6‐31G(d) density functional theory (DFT) level. The good agreement between the structural features derived from the VCD spectra and the NMR‐based structures underlines the applicability of VCD in studying the conformation of small cyclic peptides. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.

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Improved treatment of cyclic ?-amino acids and successful prediction of ?-peptide secondary structure using a modified force field: AMBER*C

Cited by 32 publications

References 66 publications

Biological and conformational study of β‐substituted prolines in MT‐II template: steric effects leading to human MC5 receptor selectivity*

Biological and conformational study of β‐substituted prolines in MT‐II template: steric effects leading to human MC5 receptor selectivity*

Theoretical Study of -Peptide Models: Intrinsic Preferences of Helical Structures

VCD studies on cyclic peptides assembled from L‐α‐amino acids and a trans‐2‐aminocyclopentane‐ or trans‐2‐aminocyclohexane carboxylic acid

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