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.