An Anchor-Dependent Molecular Docking Process for Docking Small Flexible Molecules into Rigid Protein Receptors

Abstract

A molecular docking method designated as ADDock, anchor-dependent molecular docking process for docking small flexible molecules into rigid protein receptors, is presented in this article. ADDock makes the bond connection lists for atoms based on anchors chosen for building molecular structures for docking small flexible molecules or ligands into rigid active sites of protein receptors. ADDock employs an extended version of piecewise linear potential for scoring the docked structures. Since no translational motion for small molecules is implemented during the docking process, ADDock searches the best docking result by systematically changing the anchors chosen, which are usually the single-edge connected nodes or terminal hydrogen atoms of ligands. ADDock takes intact ligand structures generated during the docking process for computing the docked scores; therefore, no energy minimization is required in the evaluation phase of docking. The docking accuracy by ADDock for 92 receptor-ligand complexes docked is 91.3%. All these complexes have been docked by other groups using other docking methods. The receptor-ligand steric interaction energies computed by ADDock for some sets of active and inactive compounds selected and docked into the same receptor active sites are apparently separated. These results show that based on the steric interaction energies computed between the docked structures and receptor active sites, ADDock is able to separate active from inactive compounds for both being docked into the same receptor.

Design of New Second‐Generation TRK Inhibitors Targeting Tropomyosin Receptor Kinases by Using Molecular Docking, Molecular Dynamics Simulations and ADMET Properties

“…Molecular docking is the preferred method for predicting the orientation of a molecule (ligand) when it binds to another molecule (receptor) such as a protein or enzyme [29] . In this study, a semi‐flexible docking approach was used to form stable complexes.…”

“…Molecular docking is the preferred method for predicting the orientation of a molecule (ligand) when it binds to another molecule (receptor) such as a protein or enzyme. [29] In this study, a semi-flexible docking approach was used to form stable complexes. This process is critical for explaining the mechanism of action or for screening lead compounds, and it is a fundamental method for structure-based drug design.…”

Virtual Screening of Some Active Human Macrophage Migration Inhibitory Factor Antagonists

“…Moreover, we employ Lipinski’s criteria 15 to screen out compounds that are unlikely to be a drug before proceeding with the molecular similarity screening process. The molecular docking program ADDock 16 is used for ranking the selected compounds from the database. Based on the docked energies computed by ADDock, we select out some 17 top-ranked compounds for testing their abilities to inhibit the MIF tautomerase experimentally.…”