This page was last updated on June 11th, 2019 at 09:04 pm
A redocking tutorial for docking peptides with disulfide bond
In this tutorial we illustrate how to re-dock a cyclic peptide into its native receptor. We will redock a 10-mer peptide from EBV into HLA-A1101 (PDB: 5GRD).
In this tutorial you will learn:
- to generate a target file for a docking in a box defined by the known peptide.
- to run ADCP to re-dock the cyclic peptides
- to understand the output of an ADCP docking run
Prerequisites:
- You have downloaded and installed the ADFRsuite 1.0
- ADFRsuite-1.0/bin in in your path (if you use a command shell in Max OS, or Linux)
- you have downloaded and unzipped the data file associated with this tutorial.
Go back to ADCP Homepage.
Generate the target file containing the affinity maps.
First lets go to the directory for this tutorial.
cd ADCP_tutorial_data/5GRDFor this tutorial, we will start directly from the PDBQT files. Please refer to the first tutorial on how to converting PDB files to PDBQT files.
agfr -r 5GRD_recH.pdbqt -l 5GRD_pepH.pdbqt -o 5GRDThe command produces the following output:
MSMSLIB 1.4.4 started on ambaeCopyright M.F. Sanner (March 2000)Compilation flags ################################################################## If you used AGFR in your work, please cite: ## ## P.A. Ravindranath S. Forli, D.S. Goodsell, A.J. Olson and ## M.F. Sanner ## AutoDockFR: Advances in Protein-Ligand Docking with ## Explicitly Specified Binding Site Flexibility ## PLoS Comput Biol 11(12): e1004586 ## DOI:10.1371/journal.pcbi.1004586 ## ## P. Ananad Ravindranath and M.F. Sanner ## AutoSite: an automated approach for pseudoligands prediction ## - From ligand binding sites identification to predicting key ## ligand atoms ## Bioinformatics (2016) ## DOI:10.1093/bioinformatics/btw367 ## ## Please see http://adfr.scripps.edu for more information. ##################################################################Computing grids on ambae a Linux-4.15.0-47-generic-x86_64-with-debian-buster-sid computerDate Mon Jun 3 16:54:32 2019loading receptor: 5GRD_recH.pdbqtloading ligand: 5GRD_pepH.pdbqtset box using ligand Box center: 29.694 -16.993 -4.930 Box length: 24.750 33.750 19.500 Box size : 66 90 52 padding : 4.000 spacing : 0.375identifying pockets using AutoSite ....Scanning at: -0.36 -0.792 -0.6clust.| Energy| # of |Rad. of | energy | bns |score |number| |points|gyration|per vol.|buriedness|v*b^2/rg|------+-------+------+--------+--------+----------+--------| 1 -39.92 73 3.10 -0.55 0.885 18.48 Scanning at: -0.315 -0.693 -0.525clust.| Energy| # of |Rad. of | energy | bns |score |number| |points|gyration|per vol.|buriedness|v*b^2/rg|------+-------+------+--------+--------+----------+--------| 1 -53.04 82 2.87 -0.65 0.907 23.49 2 -50.19 90 3.24 -0.56 0.890 22.01 Scanning at: -0.27 -0.594 -0.45clust.| Energy| # of |Rad. of | energy | bns |score |number| |points|gyration|per vol.|buriedness|v*b^2/rg|------+-------+------+--------+--------+----------+--------| 1 -170.26 313 6.04 -0.54 0.801 33.26 2 -95.79 169 4.19 -0.57 0.815 26.77 3 -47.08 85 3.15 -0.55 0.684 12.61 Scanning at: -0.225 -0.495 -0.375clust.| Energy| # of |Rad. of | energy | bns |score |number| |points|gyration|per vol.|buriedness|v*b^2/rg|------+-------+------+--------+--------+----------+--------| 1 -489.13 973 10.33 -0.50 0.739 51.37 2 -32.07 54 2.10 -0.59 0.720 13.35 found 4 pocket(s) pocket| energy | # of |Rad. of | energy | bns | score number| |points|gyration|per vol.|buriedness|v*b^2/rg ------+---------+------+--------+--------+----------+--------- 1 -208.12 447 6.30 -0.47 0.84 49.87 2 -118.34 237 4.75 -0.50 0.88 38.23 3 -45.77 97 2.82 -0.47 0.83 23.59 4 -59.14 122 3.62 -0.48 0.82 22.42 merging clusters ...done. got 119 fill Points, in 5.96 (sec)setting map types using: all to ['HS', 'Mg', 'HD', 'NA', 'Fe', 'Br', 'NS', 'A', 'C', 'Mn', 'G', 'F', 'I', 'H', 'J', 'N', 'Q', 'P', 'S', 'GA', 'Z', 'Zn', 'Cl', 'Ca', 'OA', 'SA', 'OS']computing maps for center=(29.694 -16.993 -4.930) size=(24.750 33.750 19.500) dims=(66 90 52) ... 113 points inside the box maps computed in 4.07 (sec)making target file 5GRD.trg ...done. done. 9.11 (sec)Perform the docking
Note we added two options compared with redocking the linear peptide.
-cys enables the potential for disulfide bond.
-nc 0.8 use native contacts as clustering criteria. We recommend using native contacts for larger peptides.
This calculation generates the following files:
- 5GRD_redocking_ranked_{num}.pdb # the final solutions with ranking after clustering
- 5GRD_redocking_{num}.pdb # the MC trajectory for each replica
- 5GRD_redocking_{num}.out # detailed output file for each replica
An example output is listed below:
Please note that docking cyclic peptide is extremely challenging, and the purpose of this tutorial is only to show the usage of ADCP. We suggest using more replicas with more Monte Carlo steps for real production runs.