Comparative Study of the Efficiency of Three Protein-Ligand Docking Programs

Abstract

Structure-based lead optimization approaches are increasingly playing a role in the drug-discovery process. Virtual screening by molecular docking has become a largely used approach to lead discovery in the pharmaceutical industry when a high-resolution structure of the biological target of interest is available. The performance of three docking programs (Arguslab, Autodock and FlexX), for virtual database screening, is studied. Autodock and FlexX are well established commercial packages while Arguslab is distributed freely for Windows platforms by Planaria Software. Comparisons of these docking programs and scoring functions using a large and diverse data set of pharmaceutically interesting targets and active compounds are carried out. We focus on the problem of docking and scoring flexible compounds which are sterically capable of docking into a rigid conformation of the receptor. The three dimensional structures of a carefully chosen set of 126 pharmaceutically relevant protein-ligand complexes were used for the comparative study. The Autodock methodology is shown to consistently yield enrichments superior to the two alternative methods, while FlexX outperforms largely Arguslab.

Theoretical Study of the Interactions Involved in the Inhibition of Mycobacterium Tuberculosis Methionine Aminopeptidase by Several Molecules

“…This parameter is not negligible if the software is used to screen large numbers of molecules. It is clear from this graph that the RMSD values are consistent with the results of Chikhi A and Bensegueni A [1] and Gabb et al [14 15], showing that any program the docking is successful when the RMSD is less than 2 Å. This is also consistent with the results obtained by Zaheer-ul-Haq et al [15 16], where six docking programs were used: FRED, GOLD, MOE, AutoDock, FlexX and Surflex-Dock, for a comparative study to determine their ability to reproduce poses via the experimental RMSD.…”

“…The molecular docking in silico aims to predict the structure of a molecular complex from the isolated molecules, which is considerably easier to implement, less expensive and faster than the use of experimental methods (in vitro). Docking software's are therefore very useful tools in biology, pharmacy and medicine, because most of the active site are small molecules (ligand) that interact with a biological target of therapeutic interest, usually protein (receptor), in order to influence the mechanism in which this protein is involved [1].…”

Virtual Screening Approach of Bacterial Peptide Deformylase Inhibitors Results in New Antibiotics

“…The FlexX molecular modeling program was used to conduct virtual structure screening. It is one of the best protein‐ligand docking software, it has proved to be successful in many potential hits identify applications . Several therapeutic agents have been discovered with FlexX and are on the market .…”

Are predefined decoy sets of ligand poses able to quantify scoring function accuracy?

“…Even worse, for some protein-ligand complexes no docking tool produces reliable results [3,4]. The search for the best program has resulted in a large accumulation of comparative studies of docking programs that have been published in the literature during the past few years [3][4][5][6][7][8][9][10][11][12][13][14][15]. These studies report success rates, i.e.…”