Comparative evaluation of several docking tools for docking small molecule ligands to DC-SIGN

Abstract

Five docking tools, namely AutoDock, FRED, CDOCKER, FlexX and GOLD, have been critically examined, with the aim of selecting those most appropriate for use as docking tools for docking molecules to the lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN). This lectin has been selected for its rather non-druggable binding site, which enables complex interactions that guide the binding of the core monosaccharide. Since optimal orientation is crucial for forming coordination bonds, it was important to assess whether the selected docking tools could reproduce the optimal binding conformation for several oligosaccharides that are known to bind DC-SIGN. Our results show that even widely used docking programs have certain limitations when faced with a rather shallow and featureless binding site, as is the case of DC-SIGN. The FRED docking software (OpenEye Scientific Software, Inc.) was found to score as the best tool for docking ligands to DC-SIGN. The performance of FRED was further assessed on another lectin, Langerin. We have demonstrated that this validated docking protocol could be used for docking to other lectins similar to DC-SIGN.

The discovery of a novel compound with potent antitumor activity: virtual screening, synthesis, biological evaluation and preliminary mechanism study

“…Molecular docking technology which has been increasingly used in the course of drug research and development is the representative of receptor-based virtual screening [16,17]. In this paper, molecular docking experiments were carried out using Discovery Studio 2.5 software (Accelrys Inc., San Diego, CA, USA) with fully automated docking tool using "CDOCKER" protocol [18][19][20][21][22] employing CHARMm force field to investigate the possible inhibitors for farnesyltransferase. The CDOCKER energy (-(protein-ligand interaction energies)) of best poses docked into the receptor of all the 900 compounds was calculated and compared with that of Compound 4 which is a new potent farnesyltransferase inhibitor based on the ethylenediamine scaffold.…”

An Efficient ABC_DE_Based Hybrid Algorithm for Protein–Ligand Docking

“…A scoring function [11,12,13,14,15,16] and a search algorithm [17,18,19] are the necessary tools of a docking method for solving the two goals above. The scoring function is used to evaluate the affinity between the receptor and the ligand for each conformation [20].…”

Genetic algorithm with a crossover elitist preservation mechanism for protein–ligand docking

“…Protein–ligand docking is one of the most important methods in structure-based pharmaceutical development (Brooijmans and Kuntz 2003 ; Huang and Zou 2010 ; Jug et al 2015 ; Moitessier et al 2008 ; Zhao et al 2014 , 2016 ), and it is also an important approach for large-scale virtual screening. With the development of X-ray technology, the three-dimensional structure of docked conformations has been obtained so that protein–ligand docking has more practical significance.…”