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

Abstract

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 .

Electron Density Analysis of SARS-CoV-2 RNA-Dependent RNA Polymerase Complexes

“…This limitation characterizes the boundary of the atom in Bader’s theory. The electron density was calculated in the cubic grid with the distance between nearest junctions 0.1 Å (each junction is the m th point) [ 29 , 33 , 34 ].…”

The Complementarity Principle—One More Step towards Analytical Docking on the Example of Dihydrofolate Reductase Complexes

“…Second, 3D maps of electron density were evaluated in the zones of the maximum enzyme–ligand overlap, namely in the space where the electron densities of the enzyme and the ligand are greater than 0.001 au (namely, at m points of molecular space with au and au) in the same way as it was performed in [ 7 , 8 , 9 ] for other complexes. Let us call these zones the zones of intermolecular contacts.…”

“…Recently, we investigated [ 7 , 8 , 9 ] different enzyme–ligand complexes (namely, complexes of cyclin-dependent protein kinases, mouse acetylcholinesterase, HIV-1 protease, EGFR) taken from the Protein Data Bank [ 10 , 11 ]. Three-dimensional maps of electron density were constructed for the complexes using the AlteQ method [ 12 , 13 , 14 , 15 , 16 ].…”

“…Three-dimensional maps of electron density were constructed for the complexes using the AlteQ method [ 12 , 13 , 14 , 15 , 16 ]. We found the complementarity factor which describes enzyme–ligand complementarity of the complexes without hydrogens very well [ 7 , 8 , 9 ]. It was shown that this method can be used for the search for the most correct binding poses of ligands during docking procedures [ 9 ].…”

“…We found the complementarity factor which describes enzyme–ligand complementarity of the complexes without hydrogens very well [ 7 , 8 , 9 ]. It was shown that this method can be used for the search for the most correct binding poses of ligands during docking procedures [ 9 ]. In the current paper, for the first time, a detailed assessment of the parameters of the electronic structure of enzyme–ligand complexes, taking into account hydrogen atoms, is carried out, the complementarity method was improved for these aims, and new complementarity factors were proposed.…”