PTools: an opensource molecular docking library (original) (raw)

ATTRACT and PTOOLS: Open Source Programs for Protein–Protein Docking

Computational Drug Discovery and Design, 2012

The prediction of the structure of protein-protein complexes based on structures or structural models of 8 isolated partners is of increasing importance for structural biology and bioinformatics. The ATTRACT 9 program can be used to perform systematic docking searches based on docking energy minimization. It is 10 part of the object-oriented PTools library written in Python and C++. The library contains various 11 routines to manipulate protein structures, to prepare and perform docking searches as well as analyzing 12 docking results. It also intended to facilitate further methodological developments in the area of macro-13 molecular docking that can be easily integrated. Here, we describe the application of PTools to perform 14 systematic docking searches and to analyze the results. In addition, the possibility to perform multi-15 component docking will also be presented. 16 face prediction, Normal mode analysis 18 24 (1-7) employs energy minimization in rotational and translational 25 degrees of freedom (+ potential conformational variables) of one 26 protein partner (ligand) with respect to the second protein (receptor). 27 It can be used as a stand alone program but has also been integrated 28 into the PTools molecular docking library. Flexibility of the partner 29 structures can be taken into account by representing flexible surface 30 side chains (and also loops) as multiple conformational copies. 31 The ATTRACT docking minimization employs a reduced or 32 coarse-grained protein model which is intermediated between a to account for global and local flexibility. Pro-412 teins 69, 774-780.

ClusPro: a fully automated algorithm for protein-protein docking

Nucleic Acids Research, 2004

ClusPro (http://nrc.bu.edu/cluster) represents the first fully automated, web-based program for the computational docking of protein structures. Users may upload the coordinate files of two protein structures through ClusPro's web interface, or enter the PDB codes of the respective structures, which ClusPro will then download from the PDB server (http:// www.rcsb.org/pdb/). The docking algorithms evaluate billions of putative complexes, retaining a preset number with favorable surface complementarities. A filtering method is then applied to this set of structures, selecting those with good electrostatic and desolvation free energies for further clustering. The program output is a short list of putative complexes ranked according to their clustering properties, which is automatically sent back to the user via email.

DockingShop: A Tool for Interactive Molecular Docking

2005

Given two independently determined molecular structures, the molecular docking problem predicts the bound association, or best fit between them, while allowing for conformational changes of the individual molecules during construction of a molecular complex. DockingShop is an integrated environment that permits interactive molecular docking by navigating a ligand or protein to an estimated binding site of a receptor with real-time graphical feedback of scoring factors as visual guides. Our program can be used to create initial configurations for a protein docking prediction process. Its output -the structure of a protein-ligand or protein-protein complex -may serve as an input for a protein docking algorithm, or an optimization process. This tool provides molecular graphics interfaces for structure modeling, interactive manipulation, navigation, optimization, and dynamic visualization to aid users steer the prediction process using their biological knowledge.

FireDock: a web server for fast interaction refinement in molecular docking

Nucleic Acids Research, 2008

Structural details of protein-protein interactions are invaluable for understanding and deciphering biological mechanisms. Computational docking methods aim to predict the structure of a protein-protein complex given the structures of its single components. Protein flexibility and the absence of robust scoring functions pose a great challenge in the docking field. Due to these difficulties most of the docking methods involve a two-tier approach: coarse global search for feasible orientations that treats proteins as rigid bodies, followed by an accurate refinement stage that aims to introduce flexibility into the process. The FireDock web server, presented here, is the first web server for flexible refinement and scoring of protein-protein docking solutions. It includes optimization of side-chain conformations and rigid-body orientation and allows a high-throughput refinement. The server provides a user-friendly interface and a 3D visualization of the results. A docking protocol consisting of a global search by PatchDock and a refinement by FireDock was extensively tested. The protocol was successful in refining and scoring docking solution candidates for cases taken from docking benchmarks. We provide an option for using this protocol by automatic redirection of PatchDock candidate solutions to the FireDock web server for refinement. The FireDock web server is available at

PRUNE and PROBE--two modular web services for protein-protein docking

Nucleic Acids Research, 2011

The protein-protein docking programs typically perform four major tasks: (i) generation of docking poses, (ii) selecting a subset of poses, (iii) their structural refinement and (iv) scoring, ranking for the final assessment of the true quaternary structure. Although the tasks can be integrated or performed in a serial order, they are by nature modular, allowing an opportunity to substitute one algorithm with another. We have implemented two modular web services, (i) PRUNE: to select a subset of docking poses generated during sampling search () and (ii) PROBE: to refine, score and rank them ( .ernet.in/probe). The former uses a new interface area based edge-scoring function to eliminate >95% of the poses generated during docking search. In contrast to other multi-parameter-based screening functions, this single parameter based elimination reduces the computational time significantly, in addition to increasing the chances of selecting nativelike models in the top rank list. The PROBE server performs ranking of pruned poses, after structure refinement and scoring using a regression model for geometric compatibility, and normalized interaction energy. While web-service similar to PROBE is infrequent, no web-service akin to PRUNE has been described before. Both the servers are publicly accessible and free for use.

rDock: A Fast, Versatile and Open Source Program for Docking Ligands to Proteins and Nucleic Acids

PLoS Computational Biology, 2014

Identification of chemical compounds with specific biological activities is an important step in both chemical biology and drug discovery. When the structure of the intended target is available, one approach is to use molecular docking programs to assess the chemical complementarity of small molecules with the target; such calculations provide a qualitative measure of affinity that can be used in virtual screening (VS) to rank order a list of compounds according to their potential to be active. rDock is a molecular docking program developed at Vernalis for high-throughput VS (HTVS) applications. Evolved from RiboDock, the program can be used against proteins and nucleic acids, is designed to be computationally very efficient and allows the user to incorporate additional constraints and information as a bias to guide docking. This article provides an overview of the program structure and features and compares rDock to two reference programs, AutoDock Vina (open source) and Schrö dinger's Glide (commercial). In terms of computational speed for VS, rDock is faster than Vina and comparable to Glide. For binding mode prediction, rDock and Vina are superior to Glide. The VS performance of rDock is significantly better than Vina, but inferior to Glide for most systems unless pharmacophore constraints are used; in that case rDock and Glide are of equal performance. The program is released under the Lesser General Public License and is freely available for download, together with the manuals, example files and the complete test sets, at http://rdock. sourceforge.net/ Citation: Ruiz-Carmona S, Alvarez-Garcia D, Foloppe N, Garmendia-Doval AB, Juhos S, et al. (2014) rDock: A Fast, Versatile and Open Source Program for Docking Ligands to Proteins and Nucleic Acids. PLoS Comput Biol 10(4): e1003571.

FiberDock: a web server for flexible induced-fit backbone refinement in molecular docking

2010

Protein-protein docking algorithms aim to predict the structure of a complex given the atomic structures of the proteins that assemble it. The docking procedure usually consists of two main steps: docking candidate generation and their refinement. The refinement stage aims to improve the accuracy of the candidate solutions and to identify nearnative solutions among them. During proteinprotein interaction, both side chains and backbone change their conformation. Refinement methods should model these conformational changes in order to obtain a more accurate model of the complex. Handling protein backbone flexibility is a major challenge for docking methodologies, since backbone flexibility adds a huge number of degrees of freedom to the search space. FiberDock is the first docking refinement web server, which accounts for both backbone and side-chain flexibility. Given a set of up to 100 potential docking candidates, FiberDock models the backbone and side-chain movements that occur during the interaction, refines the structures and scores them according to an energy function. The FiberDock web server is free and available with no login requirement at http://bioinfo3d.cs.tau.ac.il/FiberDock/.

The ClusPro web server for protein–protein docking

Nature Protocols, 2017

The ClusPro server (https://cluspro.org) is a widely used tool for protein-protein docking. The server provides a simple home page for basic use, requiring only two files in Protein Data Bank format. However, ClusPro also offers a number of advanced options to modify the search that include the removal of unstructured protein regions, applying attraction or repulsion, accounting for pairwise distance restraints, constructing homo-multimers, considering small angle X-ray scattering (SAXS) data, and finding heparin binding sites. Six different energy functions can be used depending on the type of proteins. Docking with each energy parameter set results in ten models defined by centers of highly populated clusters of low energy docked structures. This protocol describes the use of the various options, the construction of auxiliary restraints files, the selection of the energy parameters, and the analysis of the results. Although the server is heavily used, runs are generally completed in < 4 hours.

LightDock: a new multi-scale approach to protein–protein docking

Bioinformatics, 2017

Motivation: Computational prediction of protein-protein complex structure by docking can provide structural and mechanistic insights for protein interactions of biomedical interest. However, current methods struggle with difficult cases, such as those involving flexible proteins, low-affinity complexes or transient interactions. A major challenge is how to efficiently sample the structural and energetic landscape of the association at different resolution levels, given that each scoring function is often highly coupled to a specific type of search method. Thus, new methodologies capable of accommodating multi-scale conformational flexibility and scoring are strongly needed. Results: We describe here a new multi-scale protein-protein docking methodology, LightDock, capable of accommodating conformational flexibility and a variety of scoring functions at different resolution levels. Implicit use of normal modes during the search and atomic/coarse-grained combined scoring functions yielded improved predictive results with respect to state-of-the-art rigidbody docking, especially in flexible cases. Availability and implementation: The source code of the software and installation instructions are available for download at https://life.bsc.es/pid/lightdock/.