Local Geometry Trends and Torsional Sensitivity in N-Formyl-l-alanyl-l-alanine Amide and the Limitations of the Dipeptide Approximation

Based on a database of 11 664 RHF/4-21G ab initio gradient-optimized structures of N-formyl-l-alanyl-l-alanine amide (ALA-ALA), the local geometries and torsional sensitivity of this compound were analyzed to test the dipeptide approximation frequently used in peptide conformational analyses. This database was generated by optimizing the geometries of this compound at grid points in its four-dimensional (φ1,ψ1,φ2,ψ2) conformational space defined by 40° increments along the outer torsions φ1 and ψ2, and by 30° increments along the inner torsions ψ1 and φ2. Using cubic spline functions, the grid structures were then used to construct analytical representations of complete surfaces of the structural parameters of ALA-ALA, and of their gradients, in (φ1,ψ1,φ2,ψ2) space. Analysis of the structural surfaces shows not only that the structure of a given residue in a peptide chain depends acutely on the conformational state of a neighboring residue but also that the interresidue effects differ, depending on whethe...