How reliable could economic Hartree-Fock computations be in studying large, folded peptides? A comparative HF and DFT case study on N- and C-protected aspartic acid

Joseph C P Koo, Janice S W Lam, Salvatore J. Salpietro, Gregory A. Chass, R. D. Enriz, Ladislaus L. Torday, A. Varró, J. Papp

Research output: Contribution to journalArticle

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Abstract

In this study, potential energy hypersurfaces have been generated and analyzed for each of the nine possible backbone (BB) conformations for both the endo and exo forms of N-acetyl-L-aspartic acid N′-methylamide. Ab initio calculations were carried out at RHF/3-21G, RHF/6-31G(d), and B3LYP/6-31G(d) levels for all backbone conformations. The relative energies, as well as stabilization energies exerted by the sidechain (SC) on the backbone, were calculated for all stable conformers. All sidechain-sidechain (HO···O=C), backbone-backbone (N-H⋯O=C), and sidechain-backbone (N-H···O=C; N-H···OH) hydrogen bond interactions were analyzed. The appearance of the traditionally absent αL and εL conformers may be recognized as special geometric orientation which the aspartyl residue manifests during peptide folding or ligand docking in a receptor that contains aspartic acids in its ligand recognition sites. At all three levels of theory, there exists a trend between the hydrogen bond distance and ring size. In addition, strikingly high correlations between the torsional angles (R2 = 0.9937 for RHF/6-31G(d) versus RHF/3-21G; R2 = 0.9967 for B3LYP/6-31G(d) versus RHF/6-31G(d); R2 = 0.9914 for B3LYP/6-31G(d) versus RHF/3-21G) and between the ΔE values in kcal/mol (R2 = 0.9424 for RHF/6-31G(d) versus RHF/3-21G; R2 = 0.9108 for B3LYP/6-31G(d) versus RHF/6-31G(d); R2 = 0.9434 B3LYP/6-31G(d) versus RHF/3-21G) found at the different ab initio levels suggest that calculations carried out at the lower levels (i.e. at RHF/3-21G) are still significant.

Original languageEnglish
Pages (from-to)143-194
Number of pages52
JournalJournal of Molecular Structure: THEOCHEM
Volume619
DOIs
Publication statusPublished - Dec 9 2002

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aspartic acid
Aspartic Acid
Discrete Fourier transforms
Peptides
peptides
Conformations
economics
Hydrogen
Hydrogen bonds
Ligands
Economics
Acids
Potential energy
Stabilization
hydrogen bonds
ligands
folding
stabilization
potential energy
trends

Keywords

  • α
  • ε Helical structure
  • Aspartic acid residue
  • Density functional theory conformations
  • External hydrogen bonding
  • Helical structure
  • Internal hydrogen bonding

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Computational Theory and Mathematics
  • Atomic and Molecular Physics, and Optics

Cite this

How reliable could economic Hartree-Fock computations be in studying large, folded peptides? A comparative HF and DFT case study on N- and C-protected aspartic acid. / Koo, Joseph C P; Lam, Janice S W; Salpietro, Salvatore J.; Chass, Gregory A.; Enriz, R. D.; Torday, Ladislaus L.; Varró, A.; Papp, J.

In: Journal of Molecular Structure: THEOCHEM, Vol. 619, 09.12.2002, p. 143-194.

Research output: Contribution to journalArticle

Koo, Joseph C P ; Lam, Janice S W ; Salpietro, Salvatore J. ; Chass, Gregory A. ; Enriz, R. D. ; Torday, Ladislaus L. ; Varró, A. ; Papp, J. / How reliable could economic Hartree-Fock computations be in studying large, folded peptides? A comparative HF and DFT case study on N- and C-protected aspartic acid. In: Journal of Molecular Structure: THEOCHEM. 2002 ; Vol. 619. pp. 143-194.
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abstract = "In this study, potential energy hypersurfaces have been generated and analyzed for each of the nine possible backbone (BB) conformations for both the endo and exo forms of N-acetyl-L-aspartic acid N′-methylamide. Ab initio calculations were carried out at RHF/3-21G, RHF/6-31G(d), and B3LYP/6-31G(d) levels for all backbone conformations. The relative energies, as well as stabilization energies exerted by the sidechain (SC) on the backbone, were calculated for all stable conformers. All sidechain-sidechain (HO···O=C), backbone-backbone (N-H⋯O=C), and sidechain-backbone (N-H···O=C; N-H···OH) hydrogen bond interactions were analyzed. The appearance of the traditionally absent αL and εL conformers may be recognized as special geometric orientation which the aspartyl residue manifests during peptide folding or ligand docking in a receptor that contains aspartic acids in its ligand recognition sites. At all three levels of theory, there exists a trend between the hydrogen bond distance and ring size. In addition, strikingly high correlations between the torsional angles (R2 = 0.9937 for RHF/6-31G(d) versus RHF/3-21G; R2 = 0.9967 for B3LYP/6-31G(d) versus RHF/6-31G(d); R2 = 0.9914 for B3LYP/6-31G(d) versus RHF/3-21G) and between the ΔE values in kcal/mol (R2 = 0.9424 for RHF/6-31G(d) versus RHF/3-21G; R2 = 0.9108 for B3LYP/6-31G(d) versus RHF/6-31G(d); R2 = 0.9434 B3LYP/6-31G(d) versus RHF/3-21G) found at the different ab initio levels suggest that calculations carried out at the lower levels (i.e. at RHF/3-21G) are still significant.",
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AU - Koo, Joseph C P

AU - Lam, Janice S W

AU - Salpietro, Salvatore J.

AU - Chass, Gregory A.

AU - Enriz, R. D.

AU - Torday, Ladislaus L.

AU - Varró, A.

AU - Papp, J.

PY - 2002/12/9

Y1 - 2002/12/9

N2 - In this study, potential energy hypersurfaces have been generated and analyzed for each of the nine possible backbone (BB) conformations for both the endo and exo forms of N-acetyl-L-aspartic acid N′-methylamide. Ab initio calculations were carried out at RHF/3-21G, RHF/6-31G(d), and B3LYP/6-31G(d) levels for all backbone conformations. The relative energies, as well as stabilization energies exerted by the sidechain (SC) on the backbone, were calculated for all stable conformers. All sidechain-sidechain (HO···O=C), backbone-backbone (N-H⋯O=C), and sidechain-backbone (N-H···O=C; N-H···OH) hydrogen bond interactions were analyzed. The appearance of the traditionally absent αL and εL conformers may be recognized as special geometric orientation which the aspartyl residue manifests during peptide folding or ligand docking in a receptor that contains aspartic acids in its ligand recognition sites. At all three levels of theory, there exists a trend between the hydrogen bond distance and ring size. In addition, strikingly high correlations between the torsional angles (R2 = 0.9937 for RHF/6-31G(d) versus RHF/3-21G; R2 = 0.9967 for B3LYP/6-31G(d) versus RHF/6-31G(d); R2 = 0.9914 for B3LYP/6-31G(d) versus RHF/3-21G) and between the ΔE values in kcal/mol (R2 = 0.9424 for RHF/6-31G(d) versus RHF/3-21G; R2 = 0.9108 for B3LYP/6-31G(d) versus RHF/6-31G(d); R2 = 0.9434 B3LYP/6-31G(d) versus RHF/3-21G) found at the different ab initio levels suggest that calculations carried out at the lower levels (i.e. at RHF/3-21G) are still significant.

AB - In this study, potential energy hypersurfaces have been generated and analyzed for each of the nine possible backbone (BB) conformations for both the endo and exo forms of N-acetyl-L-aspartic acid N′-methylamide. Ab initio calculations were carried out at RHF/3-21G, RHF/6-31G(d), and B3LYP/6-31G(d) levels for all backbone conformations. The relative energies, as well as stabilization energies exerted by the sidechain (SC) on the backbone, were calculated for all stable conformers. All sidechain-sidechain (HO···O=C), backbone-backbone (N-H⋯O=C), and sidechain-backbone (N-H···O=C; N-H···OH) hydrogen bond interactions were analyzed. The appearance of the traditionally absent αL and εL conformers may be recognized as special geometric orientation which the aspartyl residue manifests during peptide folding or ligand docking in a receptor that contains aspartic acids in its ligand recognition sites. At all three levels of theory, there exists a trend between the hydrogen bond distance and ring size. In addition, strikingly high correlations between the torsional angles (R2 = 0.9937 for RHF/6-31G(d) versus RHF/3-21G; R2 = 0.9967 for B3LYP/6-31G(d) versus RHF/6-31G(d); R2 = 0.9914 for B3LYP/6-31G(d) versus RHF/3-21G) and between the ΔE values in kcal/mol (R2 = 0.9424 for RHF/6-31G(d) versus RHF/3-21G; R2 = 0.9108 for B3LYP/6-31G(d) versus RHF/6-31G(d); R2 = 0.9434 B3LYP/6-31G(d) versus RHF/3-21G) found at the different ab initio levels suggest that calculations carried out at the lower levels (i.e. at RHF/3-21G) are still significant.

KW - α

KW - ε Helical structure

KW - Aspartic acid residue

KW - Density functional theory conformations

KW - External hydrogen bonding

KW - Helical structure

KW - Internal hydrogen bonding

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U2 - 10.1016/S0166-1280(02)00579-1

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EP - 194

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