Comparison of Forcefields in the Prediction of Intrinsic Residue-Specific Backbone Dihedral Angle Distributions of Blocked Amino Acids

The intrinsic conformational preferences of amino acids in water are governed by the distributions of backbone dihedral angles, ？ and ψ. These intrinsic preferences can be gleaned from simulations of or measurements on blocked amino acids of the form N-acetyl-Xaa-N′-methylamide, where Xaa denotes the amino acid residue of interest. In these constructs, the backbone dihedral angle preferences are not influenced by local and non-local interactions that prevail in longer peptide and protein sequences. Accordingly, comparative assessments of conformational distributions extracted from simulations of blocked amino acids provide a direct route for comparing molecular mechanics forcefields. Recently Choi and Pappu developed a refined description of blocked amino acid conformational distributions that are based on a combination of coil library statistics and spectroscopic data. The refined library renders conformational distributions in terms of conformational basins that are defined by basin centers, basin envelopes, and basin weights