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Getting started with EADock DSS

Introduction Performance Parameters Output Availability and examples

Introduction

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A lot of things have changed since the previous release. Our aim with EADock DSS is to be much faster than EADock2. As a consequence, the algorithm has been completely redesigned and reimplemented. This new docking software can be used in two different ways:

  • as a fast single-step docking software
  • as a seed generator for EADock2, which is launched afterward

EADock DSS is a 3-steps process:

  • many binding modes are generated either in a box (local docking) or in the vicinity of the target cavities (blind docking). Their CHARMM energies are estimated on a grid.
  • binding modes with the most favorable energy are evaluated with FACTS and clustered.
  • the most favorable clusters are dumped in a file.



Performance

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The sampling engine of EADock DSS is several orders of magnitude faster than that of EADock2, and the docking of highly flexible ligands should be significantly better. The following table presents some preliminary success rates obtained on the 260 complexes of the LDPB using the accurate docking type:


docking type success rate @ rank 0 success rate @ rank < 5
native local 52 % 64 %
native blind 52 % 61 %
cross local 26 % 44 %

For simple dockings (low number of dihedral angles or small search space), the very fast and fast modes of SwissDock are likely to be sufficient. Here are the success rates observed on the 260 complexes of the LPDB for native blind docking:


docking type success rate @ rank 0 success rate @ rank < 5 average CPU time
very fast 36 % 43 % 4 min 29 s
fast 48 % 54 % 11 min 44 s
accurate 52 % 61 % 23 min 58 s

In other words, while the performance is slightly lower than that of EADock2, it is so much faster that you may like it a lot.


Parameters

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The usual EADock input file has disappeared. You now have a reduced set of parameters, that are defined by environment variables. Here is a short description for each of them, grouped by type.


IO, files and system definition


Environment variable name Default value Description
CHARMMBINARY <string> undefined Path to the CHARMM executable.
CHARMMPARAMETER <string> undefined Path to the CHARMM parameter file (par_all22_prot.inp).
CHARMMTOPOLOGY <string> undefined Path to the CHARMM parameter file (top_all22_prot.inp).
OUTPUTFILE <string> clusters.zip Name of the output file, which is a ZIP file containing clusters of minimized binding modes (CRD format).
DUMPTEMPFILES <true|false> false Whether temporary files should be dumped or not.
LIGANDSELECTION <string> SEGID LIG CHARMM Selection for the ligand.

About the system:

  • All CRDs, RTF and PAR files that are in the current working directory will be loaded.
  • A single PSF is allowed.


Sampling


Environment variable name Default value Description
XMIN <float>
XMAX <float>
YMIN <float>
YMAX <float>
ZMIN <float>
ZMAX <float>
 undefined Definition of the search space. If these variables are not defined, a blind docking is performed.
WANTEDCONFS <integer> 5000 Number of binding modes that should be sampled
NBFACTSEVAL <integer> 350 Number of most favorable sampled binding modes that will be evaluated with FACTS before being clustered
NBSEEDS <integer> 250 Number of binding modes that should be dumped in OUTPUTFILE (see above)
IGNOREPOCKETBIAS <boolean> false Controls whether the sampling should be biased toward binding pockets.
USETRANSLATIONS <boolean> true Controls whether translations are used during the docking or if an in situ optimization is preferred.

Minimization scheme


Environment variable name Default value Description
SDSTEPS <integer> 200 Number of steps of SD minimization
ABNRSTEPS <integer> 500 Number of steps of ABNR minimization
PASSIVEFLEXIBILITYDISTANCE <float> 0 The PASSIVEFLEXIBILITYDISTANCE allows side chains that are closer than the distance from any atom of the ligand in its reference binding mode to be co-minimized with the ligand. This is roughly equivalent to the passive induced fit implemented in EADock2 and is currently being assessed.
PASSIVEFLEXIBILITYSELECTION <CHARMM selection> none The PASSIVEFLEXIBILITYSELECTION allows the defined selection to be optimized during the mimization steps following the DSS search. This is roughly equivalent to the passive induced fit implemented in EADock2 and is currently being assessed.

Clustering parameters


Environment variable name Default value Description
CLUSTERINGRADIUS <float> 2.0 Clustering radius
MAXCLUSTERSIZE <integer> 8 Maximum number of elements in a cluster.
FORCECLUSTERSIZE <boolean> false Force the size of the clusters. If needed, new elements are generated starting from its members (randomly selected), using EADock2's smart operators, namely SoftLigand, VdwOptimizer and ElectrostaticOptimizer. In the end, exactly NBSEEDS are produced. This flag should be activated if EADock2 is to be used afterwards.


Output

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File name Content
full_grid.pdb temporary file #1 (full grid)
filtered_list.pdb temporary file #2 (reduced grid)
generated.zip temporary file #3 (all generated binding modes)
seeds.zip temporary file #4 (minimized binding modes)
clusters.zip main output file, zip file containing clusters of minimized binding modes
summary.csv summary of sampled binding modes

Availability and examples

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Online use



Offline use


  • EADock DSS is available in /usr/local/bioinfo/eadock3.
  • Sample system files can be downloaded here.
  • Here is a sample shell script to launch EADock DSS. You probably do not want to export environment variables outside of your launcher script, but add a trailing \ to each line so that they are all interpreted as a single one.

#!/bin/bash
WANTEDCONFS=5000 \
NBFACTSEVAL=250 \
NBSEEDS=250 \
SDSTEPS=100 \
ABNRSTEPS=250 \
CLUSTERINGRADIUS=2 \
MAXCLUSTERSIZE=8 \
FORCECLUSTERSIZE=true \
DUMPTEMPFILES=true \
OUTPUTFILE=clusters.zip \
CHARMMBINARY=/usr/local/bioinfo/c35b1r1/exec/gnu/c35b1r1-xxlarge-32bits-gfortran \
CHARMMPARAMETER=/usr/local/bioinfo/c35b1r1/toppar/par_all22_prot.inp \
CHARMMTOPOLOGY=/usr/local/bioinfo/c35b1r1/toppar/top_all22_prot.inp \
java -jar -Xmx2048m eadock3.jar >eadock3.out 2>eadock3.err
 

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