Atomic Property Fields: Generalized 3D Pharmacophoric Potential for Automated Ligand Superposition, Pharmacophore Elucidation and 3D QSAR

The atomic property fields (APF) concept is introduced as a continuous, multi‐component 3D potential that reflects preferences for various atomic properties at each point in space. Atomic property field‐based approaches to several key problems in the field of ligand structure‐based rational drug discovery and design are investigated. The superposition of ligands on one or multiple molecular templates is performed by Monte‐Carlo minimization in the atomic property fields potentials combined with standard force‐field energy. The approach is extended to multiple flexible ligand alignments using an iterative procedure, Self‐Consistent atomic Property Fields by Optimization (SCAPFOld). The application of atomic property fields and SCAPFOld for virtual ligand screening and 3D Quantitive Structure‐Activity Relationship (QSAR) is tested on published benchmarks. The new methods are shown to perform competitively in comparison to current state‐of‐the‐art methods.