Density Functional Theory Study of β-Hairpins in Antiparallel β-Sheets, a New Classification Based upon H-Bond Topology

Abstract

We present a new classification of β-turns specific to antiparallel β-sheets based upon the topology of H-bond formation. This classification results from ONIOM calculations using B3LYP/D95** DFT and AM1 semiempirical calculations as the high and low levels respectively. We chose acetyl(Ala)6NH2 as a model system as it is the simplest all alanine system that can form all the H-bonds required for a β-turn in a sheet. Of the ten different conformation we have found, the most stable structures have C7 cyclic H-bonds in place of the C10 interactions specified in the classic definition. Also, the chiralities specified for the i+1st and i+2nd residues in the classic definition disappear when the structures are optimized using our techniques, as the energetic differences between the four diastereomers of each structure are not substantial for eight of the ten conformations.

The Folding of Acetyl(Ala)28NH2and Acetyl(Ala)40NH2Extended Strand Peptides into Antiparallel β-Sheets. A Density Functional Theory Study of β-Sheets with β-Turns

“…3,6 We have recently proposed a new classification of β-turns and we shall apply that classification here. 36 This classification divides β-turns into two general classes: type A (which contain a C 10 H-bond between the i th and i+3 rd residues) and type B (which lack this C 10 H-bond, but may contain one or more C 7 H-bonds). The C 7 H-bonds that we observed may be more stable than the C 10 (C N H-bonds refer to cyclic H-bonding systems that contain N atoms).…”

Exploring the conformational preferences of 20-residue peptides in isolation: Ac-Ala19-Lys + H+vs. Ac-Lys-Ala19 + H+ and the current reach of DFT

“…Due to its good compromise between efficiency and accuracy, density-functional theory (DFT) is increasingly used in the field of protein research. [30][31][32] While DFT is an exact theory in principle, the exchange-correlation functional has to be approximated though, and different approximations exist. This is critical for the study of peptide structure as conformers may eventually differ by only a few meV per residue or even less, so that small errors of the method can lead to different predictions for the most stable structures.…”

Capping Amyloid β-Sheets of the Tau-Amyloid Structure VQIVYK with Hexapeptides Designed To Arrest Growth. An ONIOM and Density Functional Theory Study

“…The current procedure also gave relative energies that agreed well with complete DFT optimizations for a series of five small 3 10 -helical peptides. 18 We have used this procedure with success for several previous studies of peptide structures, 3 , 4 , 16 , 18 − 24 and have shown it to compare favorably with other functional/basis set combinations for calculations on the gas phase water dimer. 25 …”