Assessing the One-Bond C_α-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) ¹J_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 ¹J_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 ¹J_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.