Assessing the Performance of Popular Quantum Mechanics and Molecular Mechanics Methods and Revealing the Sequence-Dependent Energetic Features Using 100 Tetrapeptide Models

Abstract

A reasonable description of the conformation energies of each of the amino acids is crucial for modeling protein structures and dynamics. We here used 20 tetrapeptides (ACE-ALA-X-ALA-NME, X = one of 20 amino acids) in 5 conformations (right-handed helix (αR), left-handed helix (αL), β-sheet (β), antiparallel β-sheet (βa), and polyproline II (PPII)) as structural models to investigate the relative conformation energies at the MP2/cc-pVTZ//B3LYP/6-31G** level. The results indicate that the energetic pattern (the order and the energy gap) of the five conformations bears certain resemblances among the amino acids in the same class but is quite different among the amino acids in the different classes (e.g., hydrophobic, aromatic, polar and charged classes). The MP2 energies are then used to statistically evaluate the overall performance of various methods including density functional methods (M05-2X, PBE, and B3LYP), semiempirical methods (AM1, PM3, and PM3MM), empirical polarizable force fields (AMOEBA and AM...