Assessing the one-bond Cα−H spin-spin coupling constants in proteins: pros and cons of different approaches

Abstract

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: DFT calculation, Karplus-like equation and Gaussian Process regression. The main motivation of this work is to select the best method for a fast and accurate computation of the 1J CαH SSCC, for its use on 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 lead us to the understanding that the model chosen for the DFT computations is inappropriate, and that more complex models will requiere a higher if not prohibitively computational cost. Finally, we show that Karplus-like equation and Gaussian Process regression provide faster and more accurate results than DFT-based calculations.