Prediction of order parameters based on protein NMR structure ensemble and machine learning

The fast motions of proteins at the picosecond to nanosecond timescale, known as fast dynamics, are closely related to protein conformational entropy and rearrangement, which in turn affect catalysis, ligand binding and protein allosteric effects. The most used NMR approach to study fast protein dynamics is the model free method, which uses order parameter S² to describe the amplitude of the internal motion of local group. However, to obtain order parameter through NMR experiments is quite complex and lengthy. In this paper, we present a machine learning approach for predicting backbone ¹H-¹⁵N order parameters based on protein NMR structure ensemble. A random forest model is used to learn the relationship between order parameters and structural features. Our method achieves high accuracy in predicting backbone ¹H-¹⁵N order parameters for a test dataset of 10 proteins, with a Pearson correlation coefficient of 0.817 and a root-mean-square error of 0.131.