Comprehensive Survey of Consensus Docking for High-Throughput Virtual Screening

Abstract

The rapid advances of 3D techniques for the structural determination of proteins and the development of numerous computational methods and strategies have led to identifying highly active compounds in computer drug design. Molecular docking is a method widely used in high-throughput virtual screening campaigns to filter potential ligands targeted to proteins. A great variety of docking programs are currently available, which differ in the algorithms and approaches used to predict the binding mode and the affinity of the ligand. All programs heavily rely on scoring functions to accurately predict ligand binding affinity, and despite differences in performance, none of these docking programs is preferable to the others. To overcome this problem, consensus scoring methods improve the outcome of virtual screening by averaging the rank or score of individual molecules obtained from different docking programs. The successful application of consensus docking in high-throughput virtual screening highlights the need to optimize the predictive power of molecular docking methods.

New star-shaped ligands generated by evolutionary fitting the Omicron spike inner-cavity

“…For instance, seeSAR leads from our previous work 20,21 were selected to start our previously described sequential rather than previous independent consensus strategy, similar to the one applied in our most recent work 53 . Comparisons using ranks rather than absolute docking-scores, were used as recommended by many other authors for higher prediction accuracies [54][55][56][57][58] ; 59,60 . Finally, lead tendencies to apparent and most probably erroneous high affinities such as those only due to unspecific increase in molecular weights and hydrophobicities 61,62 , were corrected with a unique LELP parameter for ligand efficiency normalization, selected among other methods [63][64][65][66] .…”

Exploring the therapeutic mechanisms of Gleditsiae Spina acting on pancreatic cancervianetwork pharmacology, molecular docking and molecular dynamics simulation

“… 47 The AutoDock Vina program features an iterated local search global optimizer, while the determination of binding energy combines both knowledge-based and empirical scoring functions. 20 In this study, the complex structures predicted by AutoDock vina were re-scored by MMPB(GB)SA to evaluate the binding mode between the active components from Gleditsiae Spina and the target protein. Compared with traditional universal scoring functions (AutoDock vina), the inadequate consideration of solvent effects can adversely affect the performance of the scoring function.…”

“…Molecular docking is a widely employed approach in drug discovery and development, utilized to evaluate the binding of potential ligands with proteins. 20 However, the docking codes, which are the backbone of virtual screening techniques, are founded on a series of simplifications that hinder a direct extrapolation to biological contexts. There exist additional physical–chemical properties, such as solubility, p K a , and log P , that could influence the path that a ligand needs to traverse before reaching its target.…”

Evolutionary-docking targeting bacterial FtsZ

“…Alternative methods using ranks rather than scores outperform the averaged results 33 . Consensus combining conformational pose and ranking approaches from several programs (i.e., AutoDockVina, rDock, AutoDock4, PLANTS) improved their isolated performances [34][35][36][37] . Similar consensus have been proposed using exponential consensus and RMSD ranks like DockECR (https://github.com/rochoa85/dockECR) 38 , or DockingPie (https://github.com/paiardin/DockingPie) 39 .…”

“…The generated children libraries can then be ranked not only by docking-scores but also by ligand efficiency parameters. Additionally, to computationally increase the probabilities of bacterial cell wall penetration, some of the bacterial eNTRY rules for drugs [36][37][38] were finally applied (i.e., primary amines and globularity).…”