Quantum chemical roots of machine-learning molecular similarity descriptors

Abstract: In this work, we explore the quantum chemical foundations of descriptors for molecular similarity. Such descriptors are key for traversing chemical compound space with machine learning. Our focus is on the Coulomb matrix and on the smooth overlap of atomic positions (SOAP). We adopt a basic framework that allows us to connect both descriptors to electronic structure theory. This framework enables us then to define two new descriptors that are more closely related to electronic structure theory, which we call Coulomb lists and smooth overlap of electron densities (SOED). By investigating their usefulness as molecular similarity descriptors, we gain new insights in how and why Coulomb matrix and SOAP work. Moreover, Coulomb lists avoid the somewhat mysterious diagonalization step of the Coulomb matrix and might provide a direct means to extract subsystem information that can be compared across Born-Oppenheimer surfaces of varying dimension. For the electron density we derive the necessary formalism to create the SOED measure in close analogy to SOAP. Since this formalism is more involved than that of SOAP, we review the essential theory, but also introduce a set of approximations that eventually allow us to work with SOED in terms of the same implementation available for the evaluation of SOAP. We focus our analysis on elementary reaction steps, where transition state structures are more similar to either reactant or product structures than the latter two are with respect to one another. The prediction of electronic energies of transition state structures can, however, be more difficult than that of stable intermediates due to multi-configurational effects. The question arises to what extent molecular similarity descriptors rooted in electronic structure theory can resolve these intricate effects.