In the present work, we explore three different approaches for the computation of the one-bond spin-spin coupling constants (SSCC) 1JCαH 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 1JCαH 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 1JCαH 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.