Question: Performing a Localized Search about pykvfinder

[jvsguerra]

Hi @egurapha,

Thank you for your positive feedback on pyKVFinder! In response to your question, yes, it is possible to run pyKVFinder on a subset of residues.

Here are two options:

• Option 1: select cavities based on the interface residues (pyKVFinder.constitutional)
  You can use the pyKVFinder.constitutional function to identify residues around the cavities and check for specific residues. Here's an example of how you can do this:

import os
import pyKVFinder

# Detection parameters
step = 0.6
probe_out = 4.0
pdb = os.path.join(os.path.dirname(pyKVFinder.__file__), 'data', 'tests', '1FMO.pdb')

# Read atomic information from PDB file
atomic = pyKVFinder.read_pdb(pdb)

# Get vertices of the 3D grid
vertices = pyKVFinder.get_vertices(atomic, probe_out=probe_out, step=step)

# Run detection
ncav, cavities = pyKVFinder.detect(atomic, vertices, probe_out=probe_out, step=step)

# Run constitutional characterization
residues = pyKVFinder.constitutional(cavities, atomic, vertices, step=step)
print(residues)
{'KAA': [['14', 'E', 'SER'], ['15', 'E', 'VAL'], ['18', 'E', 'PHE'], ['19', 'E', 'LEU'], ['100', 'E', 'PHE'], ['152', 'E', 'LEU'], ['155', 'E', 'GLU'], ['156', 'E', 'TYR'], ['292', 'E', 'LYS'], ['302', 'E', 'TRP'], ['303', 'E', 'ILE'], ['306', 'E', 'TYR']], 'KAB': [['18', 'E', 'PHE'], ['22', 'E', 'ALA'], ['25', 'E', 'ASP'], ['26', 'E', 'PHE'], ['29', 'E', 'LYS'], ['97', 'E', 'ALA'], ['98', 'E', 'VAL'], ['99', 'E', 'ASN'], ['156', 'E', 'TYR']], 'KAC': [['141', 'E', 'PRO'], ['142', 'E', 'HIS'], ['144', 'E', 'ARG'], ['145', 'E', 'PHE'], ['148', 'E', 'ALA'], ['299', 'E', 'THR'], ['300', 'E', 'THR'], ['305', 'E', 'ILE'], ['310', 'E', 'VAL'], ['311', 'E', 'GLU'], ['313', 'E', 'PRO']], 'KAD': [['122', 'E', 'TYR'], ['124', 'E', 'ALA'], ['176', 'E', 'GLN'], ['318', 'E', 'PHE'], ['320', 'E', 'GLY'], ['321', 'E', 'PRO'], ['322', 'E', 'GLY'], ['323', 'E', 'ASP']], 'KAE': [['95', 'E', 'LEU'], ['98', 'E', 'VAL'], ['99', 'E', 'ASN'], ['100', 'E', 'PHE'], ['103', 'E', 'LEU'], ['104', 'E', 'VAL'], ['105', 'E', 'LYS'], ['106', 'E', 'LEU']], 'KAF': [['123', 'E', 'VAL'], ['124', 'E', 'ALA'], ['175', 'E', 'ASP'], ['176', 'E', 'GLN'], ['181', 'E', 'GLN']], 'KAG': [['34', 'E', 'SER'], ['37', 'E', 'THR'], ['96', 'E', 'GLN'], ['106', 'E', 'LEU'], ['107', 'E', 'GLU'], ['108', 'E', 'PHE'], ['109', 'E', 'SER']], 'KAH': [['49', 'E', 'LEU'], ['50', 'E', 'GLY'], ['51', 'E', 'THR'], ['52', 'E', 'GLY'], ['53', 'E', 'SER'], ['54', 'E', 'PHE'], ['55', 'E', 'GLY'], ['56', 'E', 'ARG'], ['57', 'E', 'VAL'], ['70', 'E', 'ALA'], ['72', 'E', 'LYS'], ['74', 'E', 'LEU'], ['84', 'E', 'GLN'], ['87', 'E', 'HIS'], ['88', 'E', 'THR'], ['91', 'E', 'GLU'], ['104', 'E', 'VAL'], ['120', 'E', 'MET'], ['121', 'E', 'GLU'], ['122', 'E', 'TYR'], ['123', 'E', 'VAL'], ['127', 'E', 'GLU'], ['166', 'E', 'ASP'], ['168', 'E', 'LYS'], ['170', 'E', 'GLU'], ['171', 'E', 'ASN'], ['173', 'E', 'LEU'], ['183', 'E', 'THR'], ['184', 'E', 'ASP'], ['186', 'E', 'GLY'], ['187', 'E', 'PHE'], ['201', 'E', 'THR'], ['327', 'E', 'PHE']], 'KAI': [['131', 'E', 'HIS'], ['138', 'E', 'PHE'], ['142', 'E', 'HIS'], ['146', 'E', 'TYR'], ['174', 'E', 'ILE'], ['314', 'E', 'PHE']], 'KAJ': [['33', 'E', 'PRO'], ['89', 'E', 'LEU'], ['92', 'E', 'LYS'], ['93', 'E', 'ARG'], ['96', 'E', 'GLN'], ['349', 'E', 'GLU'], ['350', 'E', 'PHE']], 'KAK': [['157', 'E', 'LEU'], ['162', 'E', 'LEU'], ['163', 'E', 'ILE'], ['164', 'E', 'TYR'], ['185', 'E', 'PHE'], ['188', 'E', 'ALA']], 'KAL': [['49', 'E', 'LEU'], ['127', 'E', 'GLU'], ['129', 'E', 'PHE'], ['130', 'E', 'SER'], ['326', 'E', 'ASN'], ['327', 'E', 'PHE'], ['328', 'E', 'ASP'], ['330', 'E', 'TYR']], 'KAM': [['51', 'E', 'THR'], ['55', 'E', 'GLY'], ['56', 'E', 'ARG'], ['73', 'E', 'ILE'], ['74', 'E', 'LEU'], ['75', 'E', 'ASP'], ['115', 'E', 'ASN'], ['335', 'E', 'ILE'], ['336', 'E', 'ARG']], 'KAN': [['165', 'E', 'ARG'], ['166', 'E', 'ASP'], ['167', 'E', 'LEU'], ['199', 'E', 'CYS'], ['200', 'E', 'GLY'], ['201', 'E', 'THR'], ['204', 'E', 'TYR'], ['205', 'E', 'LEU'], ['206', 'E', 'ALA'], ['209', 'E', 'ILE'], ['219', 'E', 'VAL'], ['220', 'E', 'ASP'], ['223', 'E', 'ALA']], 'KAO': [['48', 'E', 'THR'], ['51', 'E', 'THR'], ['56', 'E', 'ARG'], ['330', 'E', 'TYR'], ['331', 'E', 'GLU']], 'KAP': [['222', 'E', 'TRP'], ['238', 'E', 'PHE'], ['253', 'E', 'GLY'], ['254', 'E', 'LYS'], ['255', 'E', 'VAL'], ['273', 'E', 'LEU']], 'KAQ': [['207', 'E', 'PRO'], ['208', 'E', 'GLU'], ['211', 'E', 'LEU'], ['213', 'E', 'LYS'], ['275', 'E', 'VAL'], ['277', 'E', 'LEU']], 'KAR': [['237', 'E', 'PRO'], ['238', 'E', 'PHE'], ['249', 'E', 'LYS'], ['254', 'E', 'LYS'], ['255', 'E', 'VAL'], ['256', 'E', 'ARG']]}

# Export cavities to PDB file
# NOTE: Assuming you want cavities that have residue 14 of chain E, i.e., KAA
pyKVFinder.export('cavity.pdb', cavities, None, vertices, step=step, selection=['KAA'])

• Option 2: use the ligand adjustment mode with the subset of residues as your ligand with a large ligand cutoff.

import numpy

# Detection parameters
step = 0.6
probe_out = 4.0
ligand_cutoff=10.0
pdb = os.path.join(os.path.dirname(pyKVFinder.__file__), 'data', 'tests', '1FMO.pdb')

# Read atomic information from PDB file
atomic = pyKVFinder.read_pdb(pdb)

# Get vertices of the 3D grid
vertices = pyKVFinder.get_vertices(atomic, probe_out=probe_out, step=step)

# Before detection we need to define a ligand. 
#
# We read the information in two ways, that are:
# 1. Read the ligand from a PDB file
# ligand = os.path.join(os.path.dirname(pyKVFinder.__file__), 'data', 'tests', 'ADN.pdb')
# latomic = pyKVFinder.read_pdb(ligand)
#
# 2. Define the ligand by hand: select the ligand in atomic
mask = numpy.where((atomic[:, 0] == '14') & (atomic[:, 1] == 'E') )
latomic = atomic[mask[0], ]
# Run detection with ligand adjustment
# NOTE: Use a large distance cutoff
# Adjust this cutoff according to the size of the cavity you want to detect.
ncav, cavities = pyKVFinder.detect(atomic, vertices, probe_out=probe_out, step=step, latomic=latomic, ligand_cutoff=ligand_cutoff)

# Export cavity to PDB file
pyKVFinder.export('cavity.pdb', cavities, None, vertices, step=step)

Please note that for Option 2, you may want to consider selecting patches of residues instead of single core residues in the region of interest to ensure the entire cavity is detected.

Here is a tutorial for the ligand adjustment mode: https://lbc-lnbio.github.io/pyKVFinder/_tutorial/index.html#detecting-biomolecular-cavities-with-ligand-adjustment.

I hope this helps! If you have any further questions, please feel free to ask.

[egurapha]

Hi @jvsguerra, thanks very much for the detailed explanation. The pyKVFinder.constitutional function works for me!