Chemical shift prediction for protein structure calculation and quality assessment using an optimally parameterized force field.

The exquisite sensitivity of chemical shifts as reporters of structural information, and the ability to measure them routinely and accurately, gives great import to formulations that elucidate the structure-chemical-shift relationship. Here we present a new and highly accurate, precise, and robust formulation for the prediction of NMR chemical shifts from protein structures. Our approach, shAIC (shift prediction guided by Akaikes Information Criterion), capitalizes on mathematical ideas and an information-theoretic principle, to represent the functional form of the relationship between structure and chemical shift as a parsimonious sum of smooth analytical potentials which optimally takes into account short-, medium-, and long-range parameters in a nuclei-specific manner to capture potential chemical shift perturbations caused by distant nuclei. shAIC outperforms the state-of-the-art methods that use analytical formulations. Moreover, for structures derived by NMR or structures with novel folds, shAIC delivers better overall results; even when it is compared to sophisticated machine learning approaches. shAIC provides for a computationally lightweight implementation that is unimpeded by molecular size, making it an ideal for use as a force field.