Jupyter Notebook Protein-ligand Docking tutorial (PDBe REST API) using Biobb.

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Protein-ligand Docking tutorials using BioExcel Building Blocks (biobb)

This tutorials aim to illustrate the process of protein-ligand docking , step by step, using the BioExcel Building Blocks library (biobb) . The particular examples used are based on the Mitogen-activated protein kinase 14 (p38-α) protein (PDB code 3HEC ), a well-known Protein Kinase enzyme , in complex with the FDA-approved Imatinib (PDB Ligand code STI , DrugBank Ligand Code DB00619 ) and Dasatinib (PDB Ligand code 1N1 , DrugBank Ligand Code DB01254 ), small kinase inhibitors molecules used to treat certain types of cancer .

The tutorials will guide you through the process of identifying the active site cavity (pocket) without previous knowledge, and the final prediction of the protein-ligand complex .

Code Snippets

import nglview
import ipywidgets

pdb_code = "3HEC"         # P38 + Imatinib

ligand_code = "STI"       # Imatinib

pockets_dir = "pockets"

Jupyter Notebook ipywidgets NGLview Fpocket From line 2 of fpocket/wf_vs_fpocket.ipynb

from biobb_io.api.pdb import pdb

download_pdb = "download.pdb"
prop = {
  "pdb_code": pdb_code,
  "filter": ["ATOM", "HETATM"]
}

pdb(output_pdb_path=download_pdb,
    properties=prop)

Jupyter Notebook biobb-io biobb_io From line 13 of fpocket/wf_vs_fpocket.ipynb

view = nglview.show_structure_file(download_pdb, default=True)
view.center()
view._remote_call('setSize', target='Widget', args=['','600px'])

view

Jupyter Notebook From line 26 of fpocket/wf_vs_fpocket.ipynb

from biobb_structure_utils.utils.extract_molecule import extract_molecule

pdb_protein = "pdb_protein.pdb"

extract_molecule(input_structure_path=download_pdb,
             output_molecule_path = pdb_protein)

Jupyter Notebook biobb_structure_utils biobb-structure-utils From line 34 of fpocket/wf_vs_fpocket.ipynb

view = nglview.show_structure_file(pdb_protein, default=False)
view.add_representation(repr_type='cartoon', 
                        selection='not het',
                       colorScheme = 'atomindex')
view.center()
view._remote_call('setSize', target='Widget', args=['','600px'])

view

Jupyter Notebook From line 43 of fpocket/wf_vs_fpocket.ipynb

from biobb_vs.fpocket.fpocket_run import fpocket_run

fpocket_all_pockets = "fpocket_all_pockets.zip"
fpocket_summary = "fpocket_summary.json"
prop = {
    "min_radius": 3,
    "max_radius": 6,
    "num_spheres": 35
}

fpocket_run(input_pdb_path=pdb_protein,
        output_pockets_zip = fpocket_all_pockets,
        output_summary=fpocket_summary,
        properties=prop)

Jupyter Notebook biobb_vs Fpocket biobb-vs From line 54 of fpocket/wf_vs_fpocket.ipynb

import json

with open(fpocket_summary, 'r') as json_file:
    data = json.load(json_file)
    print(json.dumps(data, indent=4))

Jupyter Notebook JSON From line 71 of fpocket/wf_vs_fpocket.ipynb

from biobb_vs.fpocket.fpocket_filter import fpocket_filter

fpocket_filter_pockets = "fpocket_filter_pockets.zip"
prop = {
    "volume": [800, 2000]
}

fpocket_filter(input_pockets_zip=fpocket_all_pockets,
                input_summary = fpocket_summary,
                output_filter_pockets_zip=fpocket_filter_pockets,
                properties=prop)

Jupyter Notebook biobb_vs Fpocket biobb-vs From line 79 of fpocket/wf_vs_fpocket.ipynb

import os
import shutil

from pathlib import Path, PurePath
import zipfile

if Path(pockets_dir).exists(): shutil.rmtree(pockets_dir) 
os.mkdir(pockets_dir)

with zipfile.ZipFile(fpocket_filter_pockets, 'r') as zip_ref:
    zip_ref.extractall(pockets_dir)

path_pockets = [str(i) for i in Path(pockets_dir).iterdir()]
path_pockets_pdb = [str(i) for i in Path(pockets_dir).iterdir() if PurePath(i).suffix == '.pdb']
path_pockets_pqr = [str(i) for i in Path(pockets_dir).iterdir() if PurePath(i).suffix == '.pqr']

Jupyter Notebook From line 93 of fpocket/wf_vs_fpocket.ipynb

import re
import random

# random colors for cavities
r = lambda: random.randint(0,255)

# load structure
view = nglview.NGLWidget()
c = view.add_component(nglview.FileStructure(pdb_protein))

# load cavities (d) and pockets (p) and create pocketNames list
c = {}
p = {}
pocketNames = []
for pock in path_pockets:
    g = re.findall('(?:pocket)(\d+)(?:_\w+)\.(\w+)', pock)
    i = g[0][0]
    suff = g[0][1]
    if not [item for item in pocketNames if ('pocket' + i) in item]: pocketNames.append(('pocket' + i, int(i)))

    if suff == 'pdb':
        c[i] = view.add_component(filename=nglview.FileStructure(pock), **{'name': 'pocket' + i})
        c[i].clear()
    else:
        p[i] = view.add_component(filename=nglview.FileStructure(pock), **{'name': 'pocket' + i})
        p[i].clear()

# sort pocket names
pocketNames.sort(key=lambda tup: tup[1])

# representation for cavities
for pock in path_pockets_pdb:
    g = re.findall('(?:pocket)(\d+)(?:_\w+)\.(\w+)', pock)
    i = g[0][0]
    c[i].add_surface(color='#cc0000',
                     radius='1.5',
                     lowResolution= True,
                     # 0: low resolution 
                     smooth=1,
                     #useWorker= True,
                     wrap= True
                    )

# representation for pockets
for pock in path_pockets_pqr:
    g = re.findall('(?:pocket)(\d+)(?:_\w+)\.(\w+)', pock)
    i = g[0][0]
    p[i].add_surface( component=i, color='skyblue', surfaceType= 'av', contour=True )

view.center()
view._remote_call('setSize', target='Widget', args=['','600px'])
view

# show pocket labels
code = """
var stage = this.stage;
var view = this.stage.viewer;
var clist_len = stage.compList.length;
var i = 0;
for(i = 0; i <= clist_len; i++){
    if(stage.compList[i] != undefined && stage.compList[i].structure != undefined && stage.compList[i].parameters.ext === 'pqr') {        

        var elm = document.createElement("div");
        elm.innerText = 'pocket' + stage.compList[i].object.name.match(/\d+/g)
        elm.style.color = "black";
        elm.style.background = "rgba(201, 149, 6, .8)";
        elm.style.padding = "8px";

        stage.compList[i].addAnnotation(stage.compList[i].structure.center, elm)
    }
}
"""

view._execute_js_code(code)

view

Jupyter Notebook NGLview Fpocket From line 111 of fpocket/wf_vs_fpocket.ipynb

mdsel = ipywidgets.Dropdown(
    options=pocketNames,
    description='Sel. pocket:',
    disabled=False,
)
display(mdsel)

Jupyter Notebook From line 190 of fpocket/wf_vs_fpocket.ipynb

from biobb_vs.fpocket.fpocket_select import fpocket_select

fpocket_cavity = "fpocket_cavity.pdb"
fpocket_pocket = "fpocket_pocket.pqr"
prop = {
    "pocket": mdsel.value
}

fpocket_select(input_pockets_zip=fpocket_filter_pockets,
                output_pocket_pdb = fpocket_cavity,
                output_pocket_pqr=fpocket_pocket,
                properties=prop)

Jupyter Notebook biobb_vs Fpocket biobb-vs From line 199 of fpocket/wf_vs_fpocket.ipynb

from biobb_vs.utils.box import box

output_box = "box.pdb"
prop = {
    "offset": 12,
    "box_coordinates": True
}

box(input_pdb_path = fpocket_pocket,
            output_pdb_path = output_box,
            properties=prop)

Jupyter Notebook biobb_vs biobb-vs From line 214 of fpocket/wf_vs_fpocket.ipynb

view = nglview.NGLWidget()
s = view.add_component(nglview.FileStructure(download_pdb))
b = view.add_component(nglview.FileStructure(output_box))
p = view.add_component(nglview.FileStructure(fpocket_pocket))
p.clear()

atomPair = [
    [ "9999:Z.ZN1", "9999:Z.ZN2" ],
    [ "9999:Z.ZN2", "9999:Z.ZN4" ],
    [ "9999:Z.ZN4", "9999:Z.ZN3" ],
    [ "9999:Z.ZN3", "9999:Z.ZN1" ],

    [ "9999:Z.ZN5", "9999:Z.ZN6" ],
    [ "9999:Z.ZN6", "9999:Z.ZN8" ],
    [ "9999:Z.ZN8", "9999:Z.ZN7" ],
    [ "9999:Z.ZN7", "9999:Z.ZN5" ],

    [ "9999:Z.ZN1", "9999:Z.ZN5" ],
    [ "9999:Z.ZN2", "9999:Z.ZN6" ],
    [ "9999:Z.ZN3", "9999:Z.ZN7" ],
    [ "9999:Z.ZN4", "9999:Z.ZN8" ]
]

# structure
s.add_representation(repr_type='cartoon', 
                        selection='not het',
                        color='#cccccc',
                       opacity=.2)
# ligands box
b.add_representation(repr_type='ball+stick',
                     selection='9999',
                     color='pink', 
                     aspectRatio = 8)
# lines box
b.add_representation(repr_type='distance', 
                     atomPair= atomPair,
                     labelVisible=False,
                     color= 'black')

# pocket
p.add_surface(component=mdsel.value, 
              color='skyblue', 
              surfaceType= 'av', 
              lowResolution= True,
              # 0: low resolution 
              smooth=1,
              contour=True,
              opacity=0.4,
              #useWorker= True,
              wrap= True )


view.center()
view._remote_call('setSize', target='Widget', args=['','600px'])

view

Jupyter Notebook NGLview From line 228 of fpocket/wf_vs_fpocket.ipynb

from biobb_io.api.ideal_sdf import ideal_sdf

sdf_ideal = "ideal.sdf"
prop = {
  "ligand_code": ligand_code
}

ideal_sdf(output_sdf_path=sdf_ideal,
    properties=prop)

Jupyter Notebook biobb-io From line 287 of fpocket/wf_vs_fpocket.ipynb

from biobb_chemistry.babelm.babel_convert import babel_convert

ligand = "ligand.pdb"
prop = {
    "input_format": "sdf",
    "output_format": "pdb",
    "binary_path": "obabel"
}

babel_convert(input_path = sdf_ideal,
            output_path = ligand,
            properties=prop)

Jupyter Notebook biobb_chemistry biobb-chemistry Open Babel From line 299 of fpocket/wf_vs_fpocket.ipynb

from biobb_chemistry.babelm.babel_convert import babel_convert

prep_ligand = "prep_ligand.pdbqt"
prop = {
    "input_format": "pdb",
    "output_format": "pdbqt",
    "binary_path": "obabel"
}

babel_convert(input_path = ligand,
            output_path = prep_ligand,
            properties=prop)

Jupyter Notebook biobb_chemistry biobb-chemistry Open Babel From line 314 of fpocket/wf_vs_fpocket.ipynb

from ipywidgets import HBox

v0 = nglview.show_structure_file(ligand)
v1 = nglview.show_structure_file(prep_ligand)

v0._set_size('500px', '')
v1._set_size('500px', '')

def on_change(change):
    v1._set_camera_orientation(change['new'])

v0.observe(on_change, ['_camera_orientation'])

HBox([v0, v1])

Jupyter Notebook ipywidgets From line 329 of fpocket/wf_vs_fpocket.ipynb

from biobb_structure_utils.utils.str_check_add_hydrogens import str_check_add_hydrogens

prep_receptor = "prep_receptor.pdbqt"
prop = {
    "charges": True,
    "mode": "auto"
}

str_check_add_hydrogens(input_structure_path = pdb_protein,
            output_structure_path = prep_receptor,
            properties=prop)

Jupyter Notebook biobb_structure_utils biobb-structure-utils From line 346 of fpocket/wf_vs_fpocket.ipynb

from biobb_vs.vina.autodock_vina_run import autodock_vina_run

output_vina_pdbqt = "output_vina.pdbqt"
output_vina_log = "output_vina.log"
prop = { }

autodock_vina_run(input_ligand_pdbqt_path = prep_ligand,
             input_receptor_pdbqt_path = prep_receptor,
             input_box_path = output_box,
             output_pdbqt_path = output_vina_pdbqt,
             output_log_path = output_vina_log,
             properties = prop)

Jupyter Notebook biobb_vs biobb-vs AutoDock Vina From line 360 of fpocket/wf_vs_fpocket.ipynb

from ipywidgets import HBox

models = 'all'

v0 = nglview.show_structure_file(output_vina_pdbqt, default=False)
v0.add_representation(repr_type='licorice', 
                        selection=models,
                       colorScheme= 'partialCharge')
v0.center()
v1 = nglview.show_structure_file(output_vina_pdbqt, default=False)
v1.add_representation(repr_type='ball+stick', 
                        selection=models)
v1.center()

v0._set_size('500px', '')
v1._set_size('500px', '')

def on_change(change):
    v1._set_camera_orientation(change['new'])

v0.observe(on_change, ['_camera_orientation'])

HBox([v0, v1])

Jupyter Notebook ipywidgets From line 375 of fpocket/wf_vs_fpocket.ipynb

from Bio.PDB import PDBParser
parser = PDBParser(QUIET = True)
structure = parser.get_structure("protein", output_vina_pdbqt)
models = []
for i, m in enumerate(structure):
    models.append(('model' + str(i), i))

mdsel = ipywidgets.Dropdown(
    options=models,
    description='Sel. model:',
    disabled=False,
)
display(mdsel)

Jupyter Notebook Biopython pdbparser From line 401 of fpocket/wf_vs_fpocket.ipynb

from biobb_vs.utils.extract_model_pdbqt import extract_model_pdbqt

output_pdbqt_model = "output_model.pdbqt"
prop = {
    "model": mdsel.value + 1
}

extract_model_pdbqt(input_pdbqt_path = output_vina_pdbqt,
             output_pdbqt_path = output_pdbqt_model,
            properties=prop)

Jupyter Notebook biobb_vs biobb-vs From line 417 of fpocket/wf_vs_fpocket.ipynb

from biobb_chemistry.babelm.babel_convert import babel_convert

output_pdb_model = "output_model.pdb"
prop = {
    "input_format": "pdbqt",
    "output_format": "pdb",
    "binary_path": "obabel"
}

babel_convert(input_path = output_pdbqt_model,
             output_path = output_pdb_model,
            properties=prop)

Jupyter Notebook biobb_chemistry biobb-chemistry Open Babel From line 430 of fpocket/wf_vs_fpocket.ipynb

from biobb_structure_utils.utils.cat_pdb import cat_pdb

output_structure = "output_structure.pdb"

cat_pdb(input_structure1 = pdb_protein,
             input_structure2 = output_pdb_model,
             output_structure_path = output_structure)

Jupyter Notebook biobb_structure_utils biobb-structure-utils From line 445 of fpocket/wf_vs_fpocket.ipynb

view = nglview.NGLWidget()

# v1 = Experimental Structure
#v1 = view.add_component(download_pdb)
v1 = view.add_component(nglview.FileStructure(download_pdb))

v1.clear()
v1.add_representation(repr_type='licorice', 
                     selection='STI',
                     radius=0.5)

# v2 = Docking result
#v2 = view.add_component(output_structure)
v2 = view.add_component(nglview.FileStructure(output_structure))
v2.clear()
v2.add_representation(repr_type='cartoon', colorScheme = 'sstruc')
v2.add_representation(repr_type='licorice', radius=0.5, color= 'green', selection='UNL')

view._remote_call('setSize', target='Widget', args=['','600px'])
view

# align reference and output
code = """
var stage = this.stage;
var clist_len = stage.compList.length;
var i = 0;
var s = [];
for(i = 0; i <= clist_len; i++){
    if(stage.compList[i] != undefined && stage.compList[i].structure != undefined) {        
       s.push(stage.compList[i])
    }
}
NGL.superpose(s[0].structure, s[1].structure, true, ".CA")
s[ 0 ].updateRepresentations({ position: true })
s[ 0 ].autoView()
"""

view._execute_js_code(code)

view