LightDock-Rust

Table of Contents

• 1. Introduction
• 2. Rust environment installation
• 3. Compilation
• 4. Usage and examples

1. Introduction

LightDock-Rust is a new implementation of the LightDock software in the Rust programming language. Rust was designed for performance and reliability, and it is amazingly fast and memory-efficient (no runtime or garbage collector).

Not all LightDock has been rewritten in Rust, only the simulation part of the pipeline which is lightdock3.py Python script. Moreoever, this new Rust version only has support for the DFIRE scoring function. However, residue restraints, ANM and membrane beads are fully supported.

2. Rust environment installation

For installing the Rust compiler and cargo we recommend the rustup way (an installer for the Rust programming language):

Go to the rustup main website and follow the instructions or if you are in Linux or macOS, just type in your terminal:

curl --proto '=https' --tlsv1.2 -sSf https://sh.rustup.rs | sh

If you have any question about how to install and setup Rust and cargo it is very recommended to read the first chapter of the Rust Programming Language Book.

3. Compilation

Source code of the LightDock-Rust software is available online in the official GitHub repository. Follow these instructions to compile it from source (this is the only way at the moment):

git clone https://github.com/lightdock/lightdock-rust
cd lightdock-rust
cargo build --release

First, we clone the repository from GitHub, then we move into the new repository and finally we let cargo download and compile the library dependencies for us with the most efficient target, which is release.

You may see an output like this:

    Updating crates.io index
  Downloaded serde v1.0.110
  Downloaded ppv-lite86 v0.2.8
  Downloaded libc v0.2.71
  Downloaded serde_json v1.0.53
  Downloaded serde_derive v1.0.110
  Downloaded quote v1.0.6
  Downloaded proc-macro2 v1.0.17
  Downloaded syn v1.0.27
   Compiling libc v0.2.71
   Compiling proc-macro2 v1.0.17
   Compiling unicode-xid v0.2.0
   Compiling syn v1.0.27
   Compiling getrandom v0.1.14
   Compiling cfg-if v0.1.10
   Compiling byteorder v1.3.4
   Compiling serde v1.0.110
   Compiling ryu v1.0.4
   Compiling ppv-lite86 v0.2.8
   Compiling itoa v0.4.5
   Compiling lazy_static v1.4.0
   Compiling lib3dmol v0.3.2
   Compiling memchr v1.0.2
   Compiling quote v1.0.6
   Compiling nom v3.2.1
   Compiling rand_core v0.5.1
   Compiling npy v0.4.0
   Compiling rand_chacha v0.2.2
   Compiling rand v0.7.3
   Compiling serde_derive v1.0.110
   Compiling serde_json v1.0.53
   Compiling lightdock v0.1.0 (/path/to/lightdock-rust)
    Finished release [optimized] target(s) in 1m 23s

The lightdock-rust binary will be generated at target/release/lightdock-rust. You may move or copy this binary to the path of your choice.

4. Usage and examples

You may test a real docking example:

cd example/1ppe
cp -R ../../data .
time ../../target/release/lightdock-rust setup_1ppe.json initial_positions_0.dat 100 dfire

If you execute the binary, you will get a description of the arguments needed:

./target/release/lightdock-rust 
Wrong command line. Usage: ./target/release/lightdock-rust setup_filename swarm_filename steps method

lightdock-rust is intended to be used per swarm. For example, if lightdock3_setup.py has genearted 10 swarms, you may need to run lightdock-rust for each of the swarms, from swarm_0 to swarm_9.

We will show how to run lightdock-rust in a real example in the next section.

4.1. Running lightdock-rust for 1CZY complex

• Create a new folder and download the necessary data:

 mkdir 1czy
 cd 1czy
 wget https://raw.githubusercontent.com/lightdock/lightdock-rust/master/example/1czy/1czy_protein.pdb
 wget https://raw.githubusercontent.com/lightdock/lightdock-rust/master/example/1czy/1czy_peptide.pdb
 wget https://raw.githubusercontent.com/lightdock/lightdock-rust/master/example/1czy/restraints.list

• Now run lightdock3_setup.py:

 lightdock3_setup.py 1czy_protein.pdb 1czy_peptide.pdb 400 200 --noxt --noh -anm -rst restraints.list

You will get an output like this:

[lightdock_setup] INFO: Ignoring OXT atoms
[lightdock_setup] INFO: Ignoring Hydrogen atoms
[lightdock_setup] INFO: Reading structure from 1czy_protein.pdb PDB file...
[pdb] WARNING: Possible problem: [SideChainError] Incomplete sidechain for residue MET.335
[pdb] WARNING: Possible problem: [SideChainError] Incomplete sidechain for residue ASP.337
[pdb] WARNING: Possible problem: [SideChainError] Incomplete sidechain for residue GLU.339
[pdb] WARNING: Possible problem: [SideChainError] Incomplete sidechain for residue GLN.340
[pdb] WARNING: Possible problem: [SideChainError] Incomplete sidechain for residue LYS.341
[pdb] WARNING: Possible problem: [SideChainError] Incomplete sidechain for residue GLU.344
[pdb] WARNING: Possible problem: [SideChainError] Incomplete sidechain for residue PRO.362
[pdb] WARNING: Possible problem: [SideChainError] Incomplete sidechain for residue ARG.403
[pdb] WARNING: Possible problem: [SideChainError] Incomplete sidechain for residue ARG.423
[pdb] WARNING: Possible problem: [SideChainError] Incomplete sidechain for residue ARG.440
[pdb] WARNING: Possible problem: [SideChainError] Incomplete sidechain for residue GLU.441
[pdb] WARNING: Possible problem: [SideChainError] Incomplete sidechain for residue GLU.479
[pdb] WARNING: Possible problem: [SideChainError] Incomplete sidechain for residue LYS.481
[lightdock_setup] INFO: 1281 atoms, 168 residues read.
[lightdock_setup] INFO: Ignoring OXT atoms
[lightdock_setup] INFO: Ignoring Hydrogen atoms
[lightdock_setup] INFO: Reading structure from 1czy_peptide.pdb PDB file...
[lightdock_setup] INFO: 53 atoms, 7 residues read.
[lightdock_setup] INFO: Calculating reference points for receptor 1czy_protein.pdb...
[lightdock_setup] INFO: Done.
[lightdock_setup] INFO: Calculating reference points for ligand 1czy_peptide.pdb...
[lightdock_setup] INFO: Done.
[lightdock_setup] INFO: Saving processed structure to PDB file...
[lightdock_setup] INFO: Done.
[lightdock_setup] INFO: Saving processed structure to PDB file...
[lightdock_setup] INFO: Done.
[lightdock_setup] INFO: Calculating ANM for receptor molecule...
[lightdock_setup] INFO: 10 normal modes calculated
[lightdock_setup] INFO: Calculating ANM for ligand molecule...
[lightdock_setup] INFO: 10 normal modes calculated
[lightdock_setup] INFO: Reading restraints from restraints.list
[lightdock_setup] INFO: Number of receptor restraints is: 1 (active), 0 (passive)
[lightdock_setup] INFO: Number of ligand restraints is: 0 (active), 0 (passive)
[lightdock_setup] INFO: Calculating starting positions...
[lightdock_setup] INFO: Generated 10 positions files
[lightdock_setup] INFO: Done.
[lightdock_setup] INFO: Number of swarms is 10 after applying restraints
[lightdock_setup] INFO: Preparing environment
[lightdock_setup] INFO: Done.
[lightdock_setup] INFO: LightDock setup OK

• If ANM is enabled (it is in this example), we should convert the ANM NumPy information from 3D to 1D data using the lgd_flatten.py script:

lgd_flatten.py lightdock_rec.nm.npy rec_nm.npy
lgd_flatten.py lightdock_lig.nm.npy lig_nm.npy

• Now we can test lightdock-rust simulating the first swarm:

cd swarm_0
cp ../lightdock_1czy_protein.pdb ../lightdock_1czy_peptide.pdb .
cp ../rec_nm.npy ../lig_nm.npy .
cp -R ../../../data .
time ../../../target/release/lightdock-rust ../setup.json ../init/initial_positions_0.dat 100 dfire

Output should be similar to this:

Reading starting positions from "../init/initial_positions_0.dat"
Reading receptor input structure: lightdock_1czy_protein.pdb
Reading ligand input structure: lightdock_1czy_peptide.pdb
Loading DFIRE scoring function
Creating GSO with 200 glowworms
Starting optimization (100 steps)
Step 1
Step 2
Step 3
Step 4
Step 5
Step 6
Step 7
Step 8
Step 9
...
Step 98
Step 99
Step 100
real    0m5.152s
user    0m3.975s
sys     0m1.117s

We recommend to use ant_thony.py for parallelizing this execution. Copy the lightdock-rust binary to the current 1czy folder:

cd 1czy
cp ../target/release/lightdock-rust .

Create a new execution.sh file with the following content:

#!/bin/bash

# Edit only the number of cores to use for this simulation
NUM_CORES=4

# LightDock setup
lightdock3_setup.py 1czy_protein.pdb 1czy_peptide.pdb 400 200 --noxt --noh -anm -rst restraints.list

# Convert ANM data
lgd_flatten.py lightdock_rec.nm.npy rec_nm.npy
lgd_flatten.py lightdock_lig.nm.npy lig_nm.npy

# Calculate number of swarms
s=`ls -d swarm_* | wc -l`
swarms=$((s-1))

# Copy binary
cp ../../target/release/lightdock-rust .

# Create a task.list file for ant_thony
for i in `seq 0 $swarms`;do echo "cd swarm_${i}; cp ../lightdock_1czy_protein.pdb .; cp ../lightdock_1czy_peptide.pdb .;cp ../rec_nm.npy .;cp ../lig_nm.npy .;cp -R ../../../data .;../lightdock-rust ../setup.json ../init/initial_positions_${i}.dat 10 dfire; rm -rf lightdock_*.pdb *.npy data;" >> task.list; done

# Let ant_thony run
ant_thony.py --cores ${NUM_CORES} task.list

# Clean task.list
rm -rf task.list

Save it and then execute it (make sure you change the NUM_CORES variable according to your number of CPU cores available in your machine:

chmod u+x execution.sh
./execution.sh

After this, the docking simulation of the 1CZY protein-peptide complex using the A.PHE.377 as residue restraint should finish successfully.

$ find . -name gso_10.out | wc -l
10