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.