Use of the Complementarity Principle in Docking Procedures: A New Approach for Evaluating the Correctness of Binding Poses

Even though the first docking procedures were developed almost 40 years ago, they are still under intense development, alongside with their validation. In this article, we are proposing the use of the quantum free-orbital AlteQ method in evaluating the correctness of ligand binding poses and their ranking. The AlteQ method calculates the electron density in the interspace between the ligand and the receptor, and since their interactions follow the maximum complementarity principle, an equation can be obtained, which describes these interactions. In this way, the AlteQ method evaluates the quality of contacts between the ligand and the receptor, bypasses the drawbacks of using ligand RMSD as a measure of docking quality, and can be considered as an improvement of the “fraction of recovered ligand–receptor contacts” method. Free Windows and Linux versions of the AlteQ program for assessing complementarity between the ligand and the receptor are available for download at www.chemosophia.com.