Molecular structure does not easily identify the intricate non-covalent interactions that govern many areas of biology and chemistry, including design of new materials and drugs. We develop an approach to detect non-covalent interactions in real space, based on the electron density and its derivatives. Our approach reveals underlying chemistry that compliments the covalent structure. It provides a rich representation of van der Waals interactions, hydrogen bonds, and steric repulsion in small molecules, molecular complexes, and solids. Most importantly, the method, requiring only knowledge of the atomic coordinates, is efficient and applicable to large systems, such as proteins or DNA. Across these applications, a view of non-bonded interactions emerges as continuous surfaces rather than close contacts between atom pairs, offering rich insight into the design of new and improved ligands.

Density functional theory of electronic structure is widely and successfully applied in simulations throughout engineering and sciences. However, for many predicted properties, there are spectacular failures that can be traced to the delocalization error and static correlation error of commonly used approximations. These errors can be characterized and understood through the perspective of fractional charges and fractional spins introduced recently. Reducing these errors will open new frontiers for applications of density functional theory.

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