A versatile component-coupling model to account for substituent effects: Application to polypeptide ϕ and χ1 torsion related 3J data

A model is proposed for collating fundamental and incremental component couplings to account for substituent effects on 3J arising from, for example, amino-acid type variation. The unique topology patterns encountered in each of the common amino acids were modeled by assigning substituents on a 3J coupling path to four simple categories comprising only relative positions: central (inner) vs. terminal (outer) and first-sphere vs. second-sphere. Associated increment values then reflect the influences on each 3J coupling accessible for torsion-angle determination. Facility of use of this model, in comparison with previous ones, owes to its strict limitation to no more than three Karplus coefficients for each specific torsion-angle dependency derived. The model was integrated in the concept of self-consistent 3J analysis and applied to polypeptide fragments X-N-Cα-Y and X-Cα-Cβ-Y related to torsions ϕ and χ1, respectively, yielding quantitative effects of both first- and second-sphere substituents. Regarding the polypeptide backbone, the model predicts first-sphere substituent effects on ϕ-related 3J couplings to be within experimental uncertainty because main-chain topologies are identical in most amino-acid types, except for marginal effects in glycine and proline. However, effects in excess of standard errors in 3J(ϕ) measurements are anticipated from second-sphere substituent variation. Regarding amino-acid side chains, first-sphere substituent effects on χ1-related 3J couplings were previously found pivotal to accurate torsion-angle interpretation. Taking additional second-sphere effects on 3J(χ1) into account is here demonstrated further to improve biomolecular structure analysis.