NRGsuite: a PyMOL plugin to perform docking simulations in real time using FlexAID

Ligand protein docking simulations play a fundamental role in understanding molecular recognition. Herein we introduce the NRGsuite, a PyMOL plugin that permits the detection of surface cavities in proteins, their refinements, calculation of volume and use, individually or jointly, as target binding-sites for docking simulations with FlexAID. The NRGsuite offers the users control over a large number of important parameters in docking simulations including the assignment of flexible side-chains and definition of geometric constraints. Furthermore, the NRGsuite permits the visualization of the docking simulation in real time. The NRGsuite give access to powerful docking simulations that can be used in structure-guided drug design as well as an educational tool. The NRGsuite is implemented in Python and C/C++ with an easy to use package installer. The NRGsuite is available for Windows, Linux and MacOS. Availability and implementation: http://bcb.med.usherbrooke.ca/flexaid. Contact: rafael.najmanovich@usherbroke.ca Supplementary information: Supplementary data are available at Bioinformatics online.

[1]  Bert L. de Groot,et al.  Ligand docking and binding site analysis with PyMOL and Autodock/Vina , 2010, J. Comput. Aided Mol. Des..

[2]  J. Thornton,et al.  Shape variation in protein binding pockets and their ligands. , 2007, Journal of molecular biology.

[3]  Maria I. Zavodszky,et al.  Distilling the essential features of a protein surface for improving protein-ligand docking, scoring, and virtual screening , 2002, J. Comput. Aided Mol. Des..

[4]  M. Swindells,et al.  Protein clefts in molecular recognition and function. , 1996, Protein science : a publication of the Protein Society.

[5]  Rafael Najmanovich,et al.  Analysis of subpocket selectivity and identification of potent selective inhibitors for matriptase and matriptase-2. , 2014, Journal of medicinal chemistry.

[6]  W. Delano.  The PyMOL Molecular Graphics System , 2002 .

[7]  Aurélien Grosdidier,et al.  SwissDock, a protein-small molecule docking web service based on EADock DSS , 2011, Nucleic Acids Res..

[8]  Rafael Najmanovich,et al.  FlexAID: Revisiting Docking on Non-Native-Complex Structures , 2015, J. Chem. Inf. Model..

[9]  J. Thornton,et al.  A method for localizing ligand binding pockets in protein structures , 2005, Proteins.

[10]  Kwong-Sak Leung,et al.  istar: A Web Platform for Large-Scale Protein-Ligand Docking , 2014, PloS one.

[11]  José Xavier-Neto,et al.  KVFinder: steered identification of protein cavities as a PyMOL plugin , 2014, BMC Bioinformatics.

[12]  Xavier Barril,et al.  rDock: A Fast, Versatile and Open Source Program for Docking Ligands to Proteins and Nucleic Acids , 2014, PLoS Comput. Biol..

[13]  R. Laskowski.  SURFNET: a program for visualizing molecular surfaces, cavities, and intermolecular interactions. , 1995, Journal of molecular graphics.

[14]  Arthur J. Olson,et al.  AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading , 2009, J. Comput. Chem..

[15]  Xiaoqin Zou,et al.  Scoring functions and their evaluation methods for protein-ligand docking: recent advances and future directions. , 2010, Physical chemistry chemical physics : PCCP.

[16]  Michael M. Mysinger,et al.  Automated Docking Screens: A Feasibility Study , 2009, Journal of medicinal chemistry.

[17]  Matthew L. Danielson,et al.  Computer-aided drug design platform using PyMOL , 2011, J. Comput. Aided Mol. Des..

[18]  Samuel L. DeLuca,et al.  Small-molecule ligand docking into comparative models with Rosetta , 2013, Nature Protocols.