ProPOSE: Direct Exhaustive Protein–Protein Docking with Side Chain Flexibility

2018 ◽  
Vol 14 (9) ◽  
pp. 4938-4947 ◽  
Author(s):  
Hervé Hogues ◽  
Francis Gaudreault ◽  
Christopher R. Corbeil ◽  
Christophe Deprez ◽  
Traian Sulea ◽  
...  
Keyword(s):  
Protein Docking ◽  
Side Chain ◽  
Chain Flexibility

scholarly journals FlexAID: Revisiting docking on non native-complex structures

2014 ◽  
Author(s):  
Francis Gaudreault ◽  
Rafael Najmanovich
Keyword(s):  
Virtual Screening ◽  
Small Molecule ◽  
A Priori ◽  
Scoring Function ◽  
Protein Docking ◽  
Side Chain ◽  
Complex Structures ◽  
Autodock Vina ◽  
Chain Flexibility ◽  
Better Than

Small-molecule protein docking is an essential tool in drug design and to understand molecular recognition. In the present work we introduce FlexAID, a small-molecule docking algorithm that accounts for target side-chain flexibility and utilizes a soft scoring function, i.e. one that is not highly dependent on specific geometric criteria, based on surface complementarity. The pairwise energy parameters were derived from a large dataset of true positive poses and negative decoys from the PDBbind dataset through an iterative process using Monte Carlo simulations. The prediction of binding poses is tested using the independent Astex dataset while performance in virtual screening is evaluated using a subset of the DUD dataset. We compare FlexAID to AutoDock Vina, FlexX, and rDock in an extensive number of scenarios to understand the strengths and limitations of the different programs as well as to reported results for Glide, GOLD and DOCK6 where applicable. The most relevant among these scenarios is that of docking on flexible non native-complex structures where as is the case in reality, the target conformation in the bound form is not known a priori. We demonstrate that FlexAID, unlike other programs, is robust against increasing structural variability. FlexAID obtains equivalent sampling success as GOLD and performs better than AutoDock Vina or FlexX in all scenarios against non native- complex structures. FlexAID is better than rDock when there is at least one critical side-chain movement required upon ligand binding. In virtual screening, FlexAID rescored results are comparable to those of AutoDock Vina and rDock. The higher accuracy in flexible targets where critical movements are required, intuitive PyMOL-integrated graphical user interface and free source code as well as pre-compiled executables for Windows, Linux and Mac OS make FlexAID a welcome addition to the arsenal of existing small-molecule protein docking methods.

scholarly journals Applying Side-chain Flexibility in Motifs for Protein Docking

2015 ◽  
Vol 8 ◽  
pp. GEI.S29821 ◽  
Author(s):  
Hui Liu ◽  
Feng Lin ◽  
Jian-Li Yang ◽  
Hong-Rui Wang ◽  
Xiu-Ling Liu
Keyword(s):  
Protein Structures ◽  
Region Growing ◽  
Surface Region ◽  
Shape Descriptor ◽  
Protein Docking ◽  
Side Chain ◽  
Protein Surface ◽  
Protein Motif ◽  
Chain Flexibility ◽  
Surface Patches

Conventional rigid docking algorithms have been unsatisfactory in their computational results, largely due to the fact that protein structures are flexible in live environments. In response, we propose to introduce the side-chain flexibility in protein motif into the docking. First, the Morse theory is applied to curvature labeling and surface region growing, for segmentation of the protein surface into smaller patches. Then, the protein is described by an ensemble of conformations that incorporate the flexibility of interface side chains and are sampled using rotamers. Next, a 3D rotation invariant shape descriptor is proposed to deal with the flexible motifs and surface patches; thus, pairwise complementarity matching is needed only between the convex patches of ligand and the concave patches of receptor. The iterative closest point (ICP) algorithm is implemented for geometric alignment of the two 3D protein surface patches. Compared with the fast Fourier transform-based global geometric matching algorithm and other methods, our FlexDock system generates much less false-positive docking results, which benefits identification of the complementary candidates. Our computational experiments show the advantages of the proposed flexible docking algorithm over its counterparts.

scholarly journals Refinement of Protein Docking with Atom-Atom Contact Potentials, Backbone Flexibility and Side-Chain Repacking

2017 ◽  
Vol 112 (3) ◽  
pp. 54a
Author(s):  
Taras Dauzhenka ◽  
Ivan Anishchenko ◽  
Petras J. Kundrotas ◽  
Ilya A. Vakser
Keyword(s):  
Protein Docking ◽  
Side Chain ◽  
Backbone Flexibility

scholarly journals Computational Feasibility of an Exhaustive Search of Side-Chain Conformations in Protein-Protein Docking

2018 ◽  
Vol 39 (24) ◽  
pp. 2012-2021 ◽  
Author(s):  
Taras Dauzhenka ◽  
Petras J. Kundrotas ◽  
Ilya A. Vakser
Keyword(s):  
Protein Docking ◽  
Exhaustive Search ◽  
Side Chain ◽  
Chain Conformations

Protein–Protein Docking with Simultaneous Optimization of Rigid-body Displacement and Side-chain Conformations

2003 ◽  
Vol 331 (1) ◽  
pp. 281-299 ◽  
Author(s):  
Jeffrey J. Gray ◽  
Stewart Moughon ◽  
Chu Wang ◽  
Ora Schueler-Furman ◽  
Brian Kuhlman ◽  
...  
Keyword(s):  
Rigid Body ◽  
Protein Docking ◽  
Simultaneous Optimization ◽  
Side Chain ◽  
Rigid Body Displacement ◽  
Chain Conformations
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