Consensus Docking: Improving the Reliability of Docking in a Virtual Screening Context

Abstract

Structure-based virtual screening relies on scoring the predicted binding modes of compounds docked into the target. Because the accuracy of this scoring relies on the accuracy of the docking, methods that increase docking accuracy are valuable. Here, we present a relatively straightforward method for improving the probability of identifying accurately docked poses. The method is similar in concept to consensus scoring schemes, which have been shown to increase ranking power and thus hit rates, but combines information about predicted binding modes rather than predicted binding affinities. The pose prediction success rate of each docking program alone was found in this trial to be 55% for Autodock, 58% for DOCK, and 64% for Vina. By using more than one docking program to predict the binding pose, correct poses were identified in 82% or more of cases, a significant improvement. In a virtual screen, these more reliably posed compounds can be preferentially advanced to subsequent scoring stages to improve hit rates. Consensus docking can be easily introduced into established structure-based virtual screening methodologies.

Reliability analysis and optimization of the consensus docking approach for the development of virtual screening studies

“…A very recent approach concerns the introduction of a ligand-based component within the docking protocol that consists in exploiting the ligand information relative to crystallographic ligand-protein complexes for guiding pose selection and ranking, in a sort of combined ligand/receptor-based approach 12,[39][40][41] . Surprisingly, only very few studies evaluated the possibility of combining the results of different docking methods (consensus docking) to obtain reliable ligand binding poses and to improve the success rate in VS studies, as recently reported by Houston and Walkinshaw 42 . Inspired by their analysis, we very recently assessed the reliability of a consensus docking (CD) protocol employing ten different docking procedures at the same time to improve the performance of docking from both a qualitative and a quantitative point of view 43 .…”

Dibenzosuberyl substituted polyamines and analogs of clomipramine as effective inhibitors of trypanothione reductase; molecular docking, and assessment of trypanocidal activities

“…However, docking programs (including AutoDock Vina) have more success at predicting the experimentally observed binding modes (poses) of compounds within active sites. 91,100 Our results showed a notable uniformity in the binding locations of the DBS/DBA groups of the 33 ligand structures docked, with the DBS/DBA rings clustered into four distinct binding regions (BR 1 to 4) in the active site of TR (see Fig. 1).…”

Role of computer-aided drug design in modern drug discovery

“…Combining the results from two or more scoring functions and forming a consensus has proved to be more beneficial in scoring and ranking compounds. Consensus scoring has superior accuracy, thereby improving the probability of discovering true potential hits (Cheng et al 2009;Houston and Walkinshaw 2013).…”