Abstract
Pauling and Corey proposed a pleated-sheet configuration, now called alpha-sheet, as one of the protein secondary structures in addition to alpha-helix and beta-sheet. Recently, it has been suggested that alpha-sheet is a common feature of amyloidogenic intermediates. We have investigated the stability of antiparallel beta-sheet and two conformations of alpha-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 beta-sheet is the most stable conformation, while the alpha-sheet proposed by Pauling and Corey has 13.6 kcal/mol higher free energy than the beta-sheet. The alpha-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 alpha-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 alpha-sheet and beta-sheet. The predicted amide I IR spectra of alpha-sheet shows the main band at higher frequency than beta-sheet.
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