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Added documentation for restraints, new full 4G6M example
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‎docs/4G6M.md

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![LightDock](media/lightdock_banner.png "LightDock")
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<hr>
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# LightDock 4G6M example
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This is a complete example of the LightDock protocol whwn residue restraints are specified using the [4G6M](https://www.rcsb.org/structure/4g6m) complex as an example.
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All the files used in this example can be found in the path [examples/4G6M](../examples/4G6M).
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**IMPORTANT: We recommend you to create a new folder and to copy the starting files `4G6M_rec.pdb`, `4G6M_lig.pdb` and `restraints.list` to that folder in case you would like to run this example.**
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## 1. Setup
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First, run the setup:
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```
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lightdock_setup 4G6M_rec.pdb 4G6M_lig.pdb 400 200 -anm --noxt -rst restraints.list
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```
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The output should be something like this:
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```
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@> ProDy is configured: verbosity='info'
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[lightdock_setup] INFO: Reading structure from 4G6M_rec.pdb PDB file...
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[lightdock_setup] INFO: 1782 atoms, 230 residues read.
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[lightdock_setup] INFO: Reading structure from 4G6M_lig.pdb PDB file...
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[lightdock_setup] INFO: 1194 atoms, 149 residues read.
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[lightdock_setup] INFO: Calculating reference points for receptor 4G6M_rec.pdb...
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[lightdock_setup] INFO: Done.
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[lightdock_setup] INFO: Calculating reference points for ligand 4G6M_lig.pdb...
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[lightdock_setup] INFO: Done.
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[lightdock_setup] INFO: Saving processed structure to PDB file...
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[lightdock_setup] INFO: Done.
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[lightdock_setup] INFO: Saving processed structure to PDB file...
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[lightdock_setup] INFO: Done.
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[lightdock_setup] INFO: 10 normal modes calculated
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[lightdock_setup] INFO: 10 normal modes calculated
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[lightdock_setup] INFO: Reading restraints from restraints.list
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[lightdock_setup] INFO: Number of receptor restraints is: 20 (active), 0 (passive)
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[lightdock_setup] INFO: Number of ligand restraints is: 21 (active), 0 (passive)
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[lightdock_setup] INFO: Calculating starting positions...
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[lightdock_setup] INFO: Generated 84 positions files
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[lightdock_setup] INFO: Done.
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[lightdock_setup] INFO: Number of swarms is 84 after applying restraints
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[lightdock_setup] INFO: Preparing environment
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[lightdock_setup] INFO: Done.
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[lightdock_setup] INFO: LightDock setup OK
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```
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## 2. Simulation
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We can run our simulation in a local machine or in a HPC cluster. For the first option, simply run the following command:
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```
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lightdock setup.json 100 -s fastdfire -c 8
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```
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Where the flag `-c 8` indicates LightDock to use 8 available cores. For this example we will run `100` steps of the protocol and the C implementation of the DFIRE function `-s fastdfire`.
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To run a LightDock job on a HPC cluster, a Portable Batch System (PBS) file can be generated. This PBS file defines the commands and cluster resources used for the job. A PBS file is a plain-text file that can be easily edited with any UNIX editor. For example, create a `submit_job.sh` file containing:
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```
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#PBS -N LightDock-4G6M
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#PBS -q medium
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#PBS -l nodes=1:ppn=16
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#PBS -S /bin/bash
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#PBS -d ./
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#PBS -e ./lightdock.err
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#PBS -o ./lightdock.out
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lightdock setup.json 100 -s fastdfire -c 16
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```
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This script tells the PBS queue manager to use 16 cores of a single node in a queue with name `medium`, with job name `LigthDock-4G6M` and with standard output to `lightdock.out` and error output redirected to `lightdock.err`.
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To run this script you can do it so:
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```
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qsub < submit_job.sh
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```
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## 3. Analysis
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Once the simulation has finished (it takes around 1-2 min per 10 steps per swarm), you should:
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1. Generate structures per swarm (200 glowworms per swarm in this example)
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2. Cluster predictions per swarm
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3. Generate the ranking files
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4. Filter by a percentage of satisfied restraints (>40% in this example)
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Here there is a PBS script to do so:
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```
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#PBS -N 4G6M-anal
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#PBS -q medium
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#PBS -l nodes=1:ppn=8
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#PBS -S /bin/bash
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#PBS -d ./
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#PBS -e ./analysis.err
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#PBS -o ./analysis.out
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### Calculate the number of swarms ###
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s=`ls -d ./swarm_* | wc -l`
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swarms=$((s-1))
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### Create files for Ant-Thony ###
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for i in $(seq 0 $swarms)
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do
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echo "cd swarm_${i}; lgd_generate_conformations.py ../4G6M_rec.pdb ../4G6M_lig.pdb gso_100.out 200 > /dev/null 2> /dev/null;" >> generate_lightdock.list;
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done
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for i in $(seq 0 $swarms)
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do
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echo "cd swarm_${i}; lgd_cluster_bsas.py gso_100.out > /dev/null 2> /dev/null;" >> cluster_lightdock.list;
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done
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### Generate LightDock models ###
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ant_thony.py -c 8 generate_lightdock.list;
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### Clustering BSAS (rmsd) within swarm ###
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ant_thony.py -c 8 cluster_lightdock.list;
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### Generate ranking files for filtering ###
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lgd_rank.py $s 100;
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### Filtering models by >40% of satisfied restraints ###
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lgd_filter_restraints.py --cutoff 5.0 --fnat 0.4 rank_by_scoring.list restraints.list A B > /dev/null 2> /dev/null;
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```
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When the analysis is finished, a new folder called `filtered` has been created, which contains any predicted structure which satisfies our 40% filter and a file with the ranking of these structures by LightDock DFIRE (fastdfire) energy (more positive better) `rank_filtered.list`.
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We provide for this example a compressed filtered folder [filtered.tgz](../examples/4G6M/filtered.tgz) which contains (when decompressed) a ranking `lgd_filtered_rank.list` file. For all the filtered structures, interface RMSD (i-RMSD), ligand RMSD (l-RMSD) and fraction of native contacts (fnc) according to CAPRI criteria has been calculated:
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```
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$ head lgd_filtered_rank.list
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# structure i-RMSD l-RMSD fnc Score
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swarm_83_154.pdb 2.091 2.012 0.603448 56.869
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swarm_50_151.pdb 3.082 4.001 0.327586 50.536
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swarm_7_192.pdb 1.553 1.461 0.586207 48.936
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swarm_36_168.pdb 1.132 1.385 0.827586 48.870
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swarm_48_19.pdb 3.687 4.205 0.258621 48.739
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swarm_11_136.pdb 2.231 2.390 0.448276 48.662
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swarm_52_171.pdb 3.933 4.052 0.155172 47.808
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swarm_49_183.pdb 3.589 3.775 0.258621 47.659
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swarm_48_49.pdb 1.562 2.100 0.793103 47.234
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swarm_65_93.pdb 1.282 1.130 0.844828 45.372
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```
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As you may observe, for this example our protocol seems to perform extremely well when restraints close to the true interface are specified.

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