Molecular Docking with GNINA 1.0
David Ryan Koes
Royal Society of Chemistry Chemical Information & Computer Applications Group
David Ryan Koes
Royal Society of Chemistry Chemical Information & Computer Applications Group
May 27, 2021
Get Started: https://colab.research.google.com/drive/1GXmk1v8C-c4UtyKFqIm9HnsrVYH0pI-c
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Acknowledgements¶
Andrew McNutt, Paul Francoeur, Rishal Aggarwal, Tomohide Masuda, Rocco Meli, Matthew Ragoza, Jocelyn Sunseri
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What is molecular docking?¶
Predict the most likely conformation and pose of a ligand in a protein binding site.
- Sample conformational space
- Score poses
- Ideally score equals affinity or can be used to productively rank compounds
- Score $\ne$ Free Energy
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Inherent limitations of docking¶
Docking is intended to be high-throughput and fundamentally limiting approximations are made to achieve this.
- Receptor usually kept rigid or mostly rigid (limited side-chain flexibility)
- Ligand flexibility usually limited to torsions
- No explicit solvent model
Software Lineage¶
AutoDock Vina¶
Designed and implemented by Dr. Oleg Trott at the Scripps Research Institute.
Shared no code with AutoDock.
Focus on performance. Created new scoring function optimized for pose prediction.
Open Source Apache License
Published 2009, last update (version 1.1.2) 2011
Software Lineage¶
smina
Scoring and minimization with AutoDock Vina
We forked Vina to make it easier to use, especially for custom scoring function development and ligand minimization.
(Almost) identical behavior as Autodock Vina (just easier to use).
Apache/GPL2 Open Source License
Very stable source code. In maintence mode. Features are a subset of GNINA.
!wget https://downloads.sourceforge.net/project/smina/smina.static
!wget https://github.com/gnina/gnina/releases/download/v1.0.1/gnina
!du -sh smina.static gnina
I wasn't kidding about the extra dependencies!
However, if you are going to use gnina frequently you should build it from source so it uses the versions of libraries installed on your system (especially CUDA) which will result in a much smaller executable.
!du -sh /usr/local/bin/gnina
Running GNINA¶
!chmod +x ./gnina #make executable
!./gnina
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How does it work?¶
Setup Example¶
!wget http://files.rcsb.org/download/3ERK.pdb
!grep ATOM 3ERK.pdb > rec.pdb
!obabel rec.pdb -Orec.pdb # "sanitizing" receptor for openbabel
!grep SB4 3ERK.pdb > lig.pdb
import py3Dmol
v = py3Dmol.view(height=400)
v.addModel(open('rec.pdb').read())
v.setStyle({'cartoon':{},'stick':{'radius':0.15}})
v.addModel(open('lig.pdb').read())
v.setStyle({'model':1},{'stick':{'colorscheme':'greenCarbon'}})
v.zoomTo({'model':1})