Revealing Noncovalent Interactions

TLDR

Noncovalent interactions that govern biology, chemistry, materials, and drug design are not readily apparent from molecular structure alone. The study develops a real‑space approach that uses electron density and its derivatives to detect noncovalent interactions. The method maps these interactions by analyzing electron density derivatives, providing a continuous surface representation. It reveals van der Waals forces, hydrogen bonds, and steric repulsion across small molecules, complexes, and solids, is efficient for large systems like proteins or DNA, and offers new insights for ligand design.

Abstract

Molecular structure does not easily identify the intricate noncovalent interactions that govern many areas of biology and chemistry, including design of new materials and drugs. We develop an approach to detect noncovalent interactions in real space, based on the electron density and its derivatives. Our approach reveals the 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 nonbonded interactions emerges as continuous surfaces rather than close contacts between atom pairs, offering rich insight into the design of new and improved ligands.