Quantum mechanical studies on model α-pleated sheets

Pauling and Corey proposed a pleated-sheet configuration, now called α-sheet, as one of the protein secondary structures in addition to α-helix and β-sheet. Recently, it has been suggested that α-sheet is a common feature of amyloidogenic intermediates. We have investigated the stability of antipara...

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Bibliographic Details
Published in:Journal of computational chemistry 2010-04, Vol.31 (6), p.1216-1223
Main Authors: Wu, Hao, Canfield, Alana, Adhikari, Jhashanath, Huo, Shuanghong
Format: Article
Language:English
Subjects:
Amyloid - chemistry
amyloidogenic protein
density functional theory
energy
free energy
Models, Molecular
Molecular Dynamics Simulation
Protein Structure, Secondary
Quantum Theory
self-consistent reaction field method
Spectrophotometry, Infrared
Thermodynamics
α-sheet
β-sheet
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Summary:Pauling and Corey proposed a pleated-sheet configuration, now called α-sheet, as one of the protein secondary structures in addition to α-helix and β-sheet. Recently, it has been suggested that α-sheet is a common feature of amyloidogenic intermediates. We have investigated the stability of antiparallel β-sheet and two conformations of α-sheet in solution phase using the density functional theoretical method. The peptides are modeled as two-strand acetyl-(Ala)₂-N-methylamine. Using stages of geometry optimization and single point energy calculation at B3LYP/cc-pVTZ//B3LYP/6-31G* level and including zero-point energies, thermal, and entropic contribution, we have found that β-sheet is the most stable conformation, while the α-sheet proposed by Pauling and Corey has 13.6 kcal/mol higher free energy than the β-sheet. The α-sheet that resembles the structure observed in molecular dynamics simulations of amyloidogenic proteins at low pH becomes distorted after stages of geometry optimization in solution. Whether the α-sheets with longer chains would be increasingly favorable in water relative to the increase in internal energy of the chain needs further investigation. Different from the quantum mechanics results, AMBER parm94 force field gives small difference in solution phase energy between α-sheet and β-sheet. The predicted amide I IR spectra of α-sheet shows the main band at higher frequency than β-sheet.
ISSN:0192-8651
1096-987X
DOI:10.1002/jcc.21408