Accuracy and tractability of a kriging model of intramolecular polarizable multipolar electrostatics and its application to histidine

We propose a generic method to model polarization in the context of high-rank multipolar electrostatics. This method involves the machine learning technique kriging, here used to capture the response of an atomic multipole moment of a given atom to a change in the positions of the atoms surrounding this atom. The atoms are malleable boxes with sharp boundaries, they do not overlap and exhaust space. The method is applied to histidine where it is able to predict atomic multipole moments (up to hexadecapole) for unseen configurations, after training on 600 geometries distorted using normal modes of each of its 24 local energy minima at B3LYP/apc-1 level. The quality of the predictions is assessed by calculating the Coulomb energy between an atom for which the moments have been predicted and the surrounding atoms (having exact moments). Only interactions between atoms separated by three or more bonds (“1, 4 and higher” interactions) are included in this energy error. This energy is compared with that of a central atom with exact multipole moments interacting with the same environment. The resulting energy discrepancies are summed for 328 atom–atom interactions, for each of the 29 atoms of histidine being a central atom in turn. For 80% of the 539 test configurations (outside the training set), this summed energy deviates by less than 1 kcal mol−1.