A genetic algorithm for the ligand-protein docking problem

Abstract

We analyzed the performance of a real coded "steady-state" genetic algorithm (SSGA) using a grid-based methodology in docking five HIV-1 protease-ligand complexes having known three-dimensional structures. All ligands tested are highly flexible, having more than 10 conformational degrees of freedom. The SSGA was tested for the rigid and flexible ligand docking cases. The implemented genetic algorithm was able to dock successfully rigid and flexible ligand molecules, but with a decreasing performance when the number of ligand conformational degrees of freedom increased. The docked lowest-energy structures have root mean square deviation (RMSD) with respect to the corresponding experimental crystallographic structure ranging from 0.037 Å to 0.090 Å in the rigid docking, and 0.420 Å to 1.943 Å in the flexible docking. We found that not only the number of ligand conformational degrees of freedom is an important aspect to the algorithm performance, but also that the more internal dihedral angles are critical. Furthermore, our results showed that the initial population distribution can be relevant for the algorithm performance.

Epoxy-α-Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite

“…In order to investigate the binding mode of epoxy-␣-lapachone, this compound was docked into L. (L.) amazonensis oligopeptidase B (OPBa) using the DockThor program (27). First, the three-dimensional structures of ligand molecules were built and minimized with the Avogadro 1.1 program.…”

Computational Methods to Study G-Quadruplex–Ligand Complexes

“…Automated molecular docking (AMD) is a computational method that is used to predict ligand binding to a target receptor 55 . It is a widely used approach to screen chemical libraries to identify potential selective ligands that bind to quadruplexes.…”

Exploration of the binding pocket of histone deacetylases: the design of potent and isoform-selective inhibitors

“…Gasteiger partial charges were assigned to each atom to generate a grid parameter file (gpf) and a docking parameter file (dpf). The program uses an Amber-based semiempirical force field with a molecular mechanics model for enthalpic contributions (van der Waals and hydrogen bonding) and an empirical force field model for changes in entropy on binding (Weiner et al, 1984;MacKerell and Banavali, 2000;de Magalhães et al, 2004). For validation purposes, and to assess the quality of the prepared protein structures, a series of known HDAC inhibitors were docked into the catalytic channels of the HDAC enzymes under study.…”