Tutorial: re-docking a cyclic peptide
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These pages describe version 1.0, distributed with ADFRsuite 1.0. For new work use ADCP 1.1.
This tutorial re-docks a cyclic peptide with a disulfide bond into its native receptor: a 10-mer peptide from EBV into HLA-A*11:01 (PDB 5GRD).
You will learn to:
- generate a target file for docking in a box defined by the known peptide
- run ADCP to re-dock a cyclic peptide
- understand the output of an ADCP docking run
Prerequisites: ADFRsuite 1.0 installed with ADFRsuite-1.0/bin on your PATH, and the tutorial data downloaded (see Tutorials).
1. Generate the target file
Go to the directory for this tutorial:
cd ADCP_tutorial_data/5GRDThis tutorial starts from PDBQT files. See the first tutorial for converting PDB files to PDBQT.
agfr -r 5GRD_recH.pdbqt -l 5GRD_pepH.pdbqt -o 5GRD
NoteConsole output
MSMSLIB 1.4.4 started on ambae
Copyright 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 computer
Date Mon Jun 3 16:54:32 2019
loading receptor: 5GRD_recH.pdbqt
loading ligand: 5GRD_pepH.pdbqt
set 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 : 0.375
identifying pockets using AutoSite ....
Scanning at: -0.36 -0.792 -0.6
clust.| 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 -0.525
clust.| 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 -0.45
clust.| 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 -0.375
clust.| 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)2. Dock the cyclic peptide
adcp -t 5GRD.trg -s sscsscplsk -N 20 -n 5000000 -cys -o 5GRD_redocking -ref 5GRD_pepH.pdbqt -nc 0.8Two options are added compared with the linear peptide:
| Option | Meaning |
|---|---|
-cys |
enables the potential for disulfide bonds |
-nc 0.8 |
clusters by native contacts; recommended for larger peptides |
The run writes:
| File | Content |
|---|---|
5GRD_redocking_ranked_*.pdb |
final solutions, ranked after clustering |
5GRD_redocking_*.pdb |
the Monte Carlo trajectory of each replica |
5GRD_redocking_*.out |
detailed output of each replica |
Example output (abridged; the full run lists 100 modes):
Detected 8 cores, using 8 cores
using ramaprob.data in current folder
Performing search (20 ADCP runs with 5000000 steps each) ...
0% 10 20 30 40 50 60 70 80 90 100%
|----|----|----|----|----|----|----|----|----|----|
Docking performed in 687.79 seconds, i.e. 0 hours 11 minutes 27.785609 seconds
finish calculating neighbors for 2908 poses with 4.2 seconds
mode | affinity | ref. | clust. | rmsd | energy | best |
| (kcal/mol) | fnc | size | stdv | stdv | run |
-----+------------+------+--------+------+--------+------+
1 -27.1 0.975 12 NA NA 493
2 -25.6 1.000 8 NA NA 484
3 -24.2 0.975 3 NA NA 476
4 -23.9 0.875 22 NA NA 1967
5 -23.4 0.925 3 NA NA 472
6 -22.6 0.825 30 NA NA 468
7 -22.3 0.775 4 NA NA 1975
8 -21.5 0.800 1 NA NA 498
9 -21.4 0.600 46 NA NA 2540
10 -21.3 0.825 4 NA NA 1944
11 -21.1 0.775 1 NA NA 500
12 -20.6 0.675 17 NA NA 1940
13 -20.4 0.675 1 NA NA 1977
14 -20.4 0.700 10 NA NA 436
15 -20.4 0.075 30 NA NA 1562
16 -20.3 0.725 12 NA NA 1968
17 -20.2 0.725 1 NA NA 494
18 -19.9 0.725 1 NA NA 502
...
Important
Docking cyclic peptides is very hard. This tutorial only shows how to use ADCP; for production runs, use more replicas with more Monte Carlo steps.