eFindSite

eFindSite is a tool that predicts binding pockets, residues and ligands from a given protein structure by threading methods.

This README file is written by Snigdha Thumma.

If you find this tool useful, please cite these following papers:

1. Brylinski M, Feinstein WP. (2013) eFindSite: Improved prediction of ligand binding sites in protein models using meta-threading, machine learning and auxiliary ligands. J Comput Aided Mol Des 27 (6): 551-67.

2. Feinstein WP, Brylinski M. (2014) eFindSite: Enhanced fingerprint-based virtual screening against predicted ligand binding sites in protein models. Mol Inf 33 (2): 135-50.

Prerequisites:

• GCC compiler version 4.8.5+
• Perl version 5.16.3+

---

Example:

1. First you have to download eFindSite from here https://github.com/michal-brylinski/efindsite and unzip:

   • [local]$ unzip efindsite-master.zip
   • [local]$ cd efindsite-master/
   • [efindsite-master]$ make
   • [efindsite-master]$ ls bin/
   • [bin]$ ./efindsite

2. Then install the eFindSite template libraries from here https://osf.io/mp343/( download the latest available library ) and unpack the tarball:

   • [local]$ mkdir libraries
   • [local]$ tar xzf efindsite-lib-2018-04.tar.gz -C /usr/local/libraries/
   • [local]$ tar xzf efindsite-mod-2016-06.tar.gz -C /usr/local/libraries/

3. Before running eFindSite, you need to set several environmental variables.

   • eFindSite
     • [home]$ export EF_LIB=/usr/local/libraries/efindsite-lib-2018-04
     • [home]$ export EF_MOD=/usr/local/libraries/efindsite-mod-2016-06

4. After the environmental variables are set, it’s time to run the eFindSite and efindsite_screen

   • [library]$ /usr/local/efindsite-master/bin/efindsite -s 13gsA.pdb -t 13gsA-efindsite.lst -e 13gsA.profile -o 13gsA-efindsite_test
   • [library]$ /usr/local/efindsite-master/bin/efindsite_screen -p 13gsA-efindsite.pockets.dat -s escreen-keggcomp-mar2012.gz -o 13gsA-escreen-keggcomptest
   • [library]$ /usr/local/efindsite-master/bin/efindsite_screen -p 13gsA-efindsite.pockets.dat -s escreen-zinc12_nr-mar2012.gz -o 13gsA-escreen-zinc12_nrtest

---

Mandatory arguments for eFindSite

Parameter	Optional	Name	Description
-s	N	input_file	Is the target protein structure in PDB format; you can use either experimental structure or protein model
-t	N	template-fun	Is a text file that contains information on protein templated identified for your target e.g. by eThread
-e	N	seq.profile	Is a sequence profile of the target; it can be generated by PROFILPRO
-o	N	output_name	Is used to save five output files with different extensions that store dinging site prediction results

Mandatory arguments for efindsite_scr

Parameter	Optional	Name	Description
-p	N	pocket.dat	pocket.dat is a file containing the predicted binding pockets by eFindSite
-s	N	cmp_lib	cmp_lib is a compound library used for virtual screening
-o	N	output_file	output_file will contain ranked library compounds assigned with a Tanimoto score and Z-score

---

• If eFindSite runs successfully, it should yield 5 output files with user defined input name. ** For example: the user defined input file, 13gsA-efindsite_test, has 5 outputs as seen below*

  • 13gsA-efindsite_test.pockets.dat (detailed info on predicted pockets)
  • 13gsA-efindsite_test.pockets.pdb (predicted pockets in PDB format)
  • 13gsA-efindsite_test.alignments.dat (structure alignments of templates into the target in FASTA format)
  • 13gsA-efindsite_test.templates.pdb (template structures aligned onto the target in PDB format)
  • 13gsA-efindsite_test.ligands.sdf (extracted binding ligands in SDF format)

• Open the output files and check to make sure the files contain data.

• If the output files are empty, go back and check the script.