DockingPie: a consensus docking plugin for PyMOL

Abstract

Motivation The primary strategy for predicting the binding mode of small molecules to their receptors and for performing receptor-based virtual screening studies is protein-ligand docking, which is undoubtedly the most popular and successful approach in computer-aided drug discovery. The increased popularity of docking has resulted in the development of different docking algorithms and scoring functions. Nonetheless, it is unlikely that a single approach outperforms the others in terms of reproducibility and precision. In this ground, consensus docking techniques are taking hold. Results We have developed DockingPie, an open source PyMOL plugin for individual, as well as consensus docking analyses. Smina, AutoDock Vina, ADFR, and RxDock are the four docking engines that DockingPie currently supports in an easy and extremely intuitive way, thanks to its integrated docking environment and its GUI, fully integrated within PyMOL. Availability https://github.com/paiardin/DockingPie Supplementary information Supplementary data are available at Bioinformatics online.

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] .…”

Evolutionary-docking targeting bacterial FtsZ

“…However, to predict experimental binding is challenging due to the limitations of present in silico docking algorithms, such as DW and ADV. Known limitations include fixing of the docking-cavity amino acid side-chains, eliminating water molecules, unreliable calculation of docking-scores, molecular geometry changes by force-field energy minimizations [53][54][55][56] , and unreachable chemotype/chemical spaces 38,39 . Specially the force-field failures to correctly recognize different atom types, would greatly affect the conservation of molecular geometries after minimization [47][48][49][50] .…”

“…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 . Those strategies employed different algorithms one-by-one and their results were then pooled into different calculation methods to quantify a consensus parameter.…”

“…To explore for new chemotypes derived from the PC190723 reference idc ligand, this work combined Data Warrior (DW) evolutionary library generation with ligand efficiency parameters and AutoDockVina. Rather than screening extrabig libraries of molecules, evolutionary and sequential consensus docking strategies may allow for deeper penetration into the vast chemical space 38,39 .…”

Boosting the Full Potential of PyMOL with Structural Biology Plugins

“…Although many tools are available for accomplishing each individual task, a lack of integration slows down and hampers the process. A newly developed PyMOL plugin, DockingPie [ 81 ], addresses such limitations by providing an interoperable implementation of the many tools that are needed to carry out each step of a MDo process, from the preparation of input files to the analyses of the results. Currently, the docking engines supported by DockingPie are Smina [ 82 ], Vina [ 83 ], RxDock [ 84 , 85 ] and ADFR [ 86 ] ( Figure 3 a), as well as their peculiar protocols such as the assignment of side chain flexibility or the setup of pharmacophoric restraints.…”