Assessing the One-Bond Cα–H Spin–Spin Coupling Constants in Proteins: Pros and Cons of Different Approaches

In the present work, we explore three different approaches for the computation of the one-bond spin–spin coupling constants (SSCC) 1 J CαH in proteins: density functional theory (DFT) calculations, a Karplus-like equation, and Gaussian process regression. The main motivation of this work is to select the best method for fast and accurate computation of the 1 J CαH SSCC, for its use in everyday applications in protein structure validation, refinement, and/or determination. Our initial results showed a poor agreement between the DFT-computed and observed 1 J CαH SSCC values. Further analysis leads us to the understanding that the model chosen for the DFT computations is inappropriate and that more complex models will require a higher, if not prohibitively, computational cost. Finally, we show that the Karplus-like equation and Gaussian Process regression provide faster and more accurate results than DFT-based calculations.