Current models, for instance, for deriving pharmacophores or for 3D-QSAR or docking are essentially knowledge-based, which is fine as long as we know everything. Recently, for instance, it has become necessary to introduce halogen bonds into our knowledge base. Previously, repulsive interactions were predicted for halogen bonds. We report rational techniques to predict the binding sites and properties of ligands and demonstrate their use in 3D-QSAR (CoMFA-like) techniques. Our work is based on semiempirical molecular-orbital theory, which is now apllicable to either hunders of thousands of ligands or vary large systems of 100,000 atoms or more. Models based on the electron density, local ionization energy, electron affinity and polarizability and their derivatives allow H-bond donor and acceptor potebtials and hydrophobic interactions to be mapped and used for computer-aided drug design without prior knowledge of likely binding sites.

Objective models for ligand binding characteristics from quantum mechanics

246th National Meeting (2013)

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