An integrated suite of fast docking algorithms

Abstract

The CAPRI experiment (Critical Assessment of Predicted Interactions) simulates realistic and diverse docking challenges, each case having specific properties that may be exploited by docking algorithms. Motivated by the different CAPRI challenges, we developed and implemented a comprehensive suite of docking algorithms. These were incorporated into a dynamic docking protocol, consisting of four main stages: (1) Biological and bioinformatics research aiming to predict the binding site residues, to define distance constraints between interface atoms and to analyze the flexibility of molecules; (2) Rigid or flexible docking, performed by the PatchDock or FlexDock method, which utilizes the information gathered in the previous step. Symmetric complexes are predicted by the SymmDock method; (3) Flexible refinement and re-ranking of the rigid docking solution candidates, performed by FiberDock; and finally, (4) clustering and filtering the results based on energy funnels. We analyzed the performance of our docking protocol on a large benchmark and on recent CAPRI targets. The analysis has demonstrated the importance of biological information gathering prior to docking, which significantly increased the docking success rate, and of the refinement and re-scoring stage that significantly improved the ranking of the rigid docking solutions. Our failures were mostly a result of mishandling backbone flexibility, inaccurate homology modeling, or incorrect biological assumptions. Most of the methods are available at http://bioinfo3d.cs.tau.ac.il/.

Inhibitory Potency of Withania Somnifera Extracts Against DPP-4: An in Vitro Evaluation

“…Electrostatic point charges on the molecules were calculated. The ligands were docked into the active site using the Molecular Docking software PatchDock with default parameters (Mashiach et al, 2010). PatchDock is an algorithm for calculating the docking modes of small molecules into proteinbinding sites based on their shape complementarity.…”

Integrative computational modeling of protein interactions

“…The results of the rigid-body sampling stage are clustered using a structural similarity measure that assesses the differences at the interface of the smaller (ligand) molecule (ligand r.m.s.d., used in CAPRI as an evaluation measure [8]) and then the centroids of the clusters are ranked and provided as final models. Other docking approaches have since implemented clustering algorithms [24,31,61], most using analogous similarity measures, whereas others have developed similarity measures specific for docking (e.g. fraction of common contacts [62]).…”

“…+ Integrated suite of docking tools [24]. Allows user-defined selection of 'blocked' and 'binding' residues that influence the http://zdock.umassmed.edu/ during the FFT search or as filter at the end.…”

“…The coarsegrained ATTRACT docking developed by Zacharias [38] was recently extended to allow docking using cryo-electron microscopy (cryo-EM) density maps [76]. The very efficient docking suite by Wolfson and colleagues [24] is split into different applications that perform specific tasks: PatchDock [42] generates rigidbody models based on geometric hashing techniques, FlexDock [77] introduces flexibility around hinges and FireDock [24] refines the docked models. Other specific tools deal with symmetrical assemblies [42,78].…”

Prediction of Protein Interaction Sites Using Mimotope Analysis

“…The first category consists of methods using protein sequence as the only input (Ofran & Rost, 2007;Res, et al, 2005). Methods in the second category such as molecular docking and simulation solely use structure data as input (Kozakov, et al, 2010;Mashiach, et al, 2010). Methods of the third category make use of a mimotope motif or a set of mimotope sequences together with protein sequence or structure as input .…”