inference_app.py

# Runs the full strong baseline, including smina/vina docking,
# gnina rescoring, and an input conformational ensemble.
import argparse
import os
import shutil
import subprocess

import pandas as pd
from rdkit import Chem
from rdkit.Chem import AllChem, PandasTools, rdMolTransforms

import numpy as np
from moleculekit.molecule import Molecule

import time

import gradio as gr

from gradio_molecule3d import Molecule3D

def protonate_receptor_and_ligand(protein,ligand):
    protein_out = protein.replace(".pdb","_H.pdb")
    with open(protein_out, "w") as f:
        subprocess.run(
            ["reduce", "-BUILD", protein],
            stdout=f,
            stderr=subprocess.DEVNULL,
        )
    ligand_out = ligand.replace(".pdb","_H.pdb")
    subprocess.run(["obabel", ligand, "-O", ligand_out, "-p", "7.4"])


def generate_conformers(ligand, num_confs=8):
    mol = Chem.MolFromMolFile(
         ligand.replace(".pdb","_H.pdb")
    )
    mol.RemoveAllConformers()
    mol = Chem.AddHs(mol)
    AllChem.EmbedMultipleConfs(mol, numConfs=num_confs, randomSeed=1)
    AllChem.UFFOptimizeMoleculeConfs(mol)
    with Chem.SDWriter(
         ligand.replace(".pdb","_multiple_confs.pdb")
    ) as writer:
        for cid in range(mol.GetNumConformers()):
            writer.write(mol, confId=cid)

def get_bb(points):
    """Return bounding box from a set of points (N,3)

    Parameters
    ----------
    points : numpy.ndarray
        Set of points (N,3)

    Returns
    -------
    boundingBox : list
        List of the form [xmin, xmax, ymin, ymax, zmin, zmax]

    """
    minx = np.min(points[:, 0])
    maxx = np.max(points[:, 0])

    miny = np.min(points[:, 1])
    maxy = np.max(points[:, 1])

    minz = np.min(points[:, 2])
    maxz = np.max(points[:, 2])
    bb = [[minx, miny, minz], [maxx, maxy, maxz]]
    return bb

def run_docking(protein, ligand):
    
    mol = Molecule(protein)
    mol.center()
    bb = get_bb(mol.coords)
    size_x = bb[1][0] - bb[0][0]
    size_y = bb[1][1] - bb[0][1]
    size_z = bb[1][2] - bb[0][2]

    subprocess.run(
        [
            "gnina",
            "-r",
            protein.replace(".pdb","_H.pdb"),
            "-l",
            ligand.replace(".sdf","_ligand_multiple_confs.sdf"),
            "-o",
            ligand.replace(".sdf","_multiple_confs_poses.sdf"),
            "--center_x",  # bounding box matching PoseBusters methodology
            str(0),
            "--center_y",
            str(0),
            "--center_z",
            str(0),
            "--size_x",
            str(size_x),
            "--size_y",
            str(size_y),
            "--size_z",
            str(size_z),
            "--scoring",
            "vina",
            "--exhaustiveness",
            "4",
            "--num_modes",
            "1",
            "--seed",
            "1",
        ]
    )
    # sort the poses from the multiple conformation runs, so overall best is first
    poses = PandasTools.LoadSDF(
         ligand.replace(".sdf","_multiple_confs_poses.sdf")
    )
    poses["CNNscore"] = poses["CNNscore"].astype(float)
    gnina_order = poses.sort_values("CNNscore", ascending=False).reset_index(drop=True)
    PandasTools.WriteSDF(
        gnina_order,
        ligand.replace(".sdf","_multiple_confs_poses.sdf"),
        properties=list(poses.columns),
    )
    return poses["CNNscore"]


def predict (input_sequence, input_ligand,input_msa, input_protein):
    start_time = time.time()

    protonate_receptor_and_ligand(input_protein, input_ligand)
    generate_conformers(input_protein, input_ligand)
    cnn_score = run_docking(input_protein, input_ligand)
    metrics = {"cnn_score": cnn_score}
    end_time = time.time()
    run_time = end_time - start_time
    return ["test_out.pdb", "test_docking_pose.sdf"], metrics, run_time

with gr.Blocks() as app:

    gr.Markdown("# Template for inference")

    gr.Markdown("Title, description, and other information about the model")   
    with gr.Row():
        input_sequence = gr.Textbox(lines=3, label="Input Protein sequence (FASTA)")
        input_ligand = gr.Textbox(lines=3, label="Input ligand SMILES")
    with gr.Row():
        input_msa = gr.File(label="Input Protein MSA (A3M)")
        input_protein = gr.File(label="Input protein monomer")
        
    
    # define any options here

    # for automated inference the default options are used
    # slider_option = gr.Slider(0,10, label="Slider Option")
    # checkbox_option = gr.Checkbox(label="Checkbox Option")
    # dropdown_option = gr.Dropdown(["Option 1", "Option 2", "Option 3"], label="Radio Option")

    btn = gr.Button("Run Inference")

    gr.Examples(
        [
            [
                "SVKSEYAEAAAVGQEAVAVFNTMKAAFQNGDKEAVAQYLARLASLYTRHEELLNRILEKARREGNKEAVTLMNEFTATFQTGKSIFNAMVAAFKNGDDDSFESYLQALEKVTAKGETLADQIAKAL:SVKSEYAEAAAVGQEAVAVFNTMKAAFQNGDKEAVAQYLARLASLYTRHEELLNRILEKARREGNKEAVTLMNEFTATFQTGKSIFNAMVAAFKNGDDDSFESYLQALEKVTAKGETLADQIAKAL",
                "COc1ccc(cc1)n2c3c(c(n2)C(=O)N)CCN(C3=O)c4ccc(cc4)N5CCCCC5=O",
                "test_out.pdb"
            ],
        ],
        [input_sequence, input_ligand, input_protein],
    )
    reps =    [
    {
      "model": 0,
      "style": "cartoon",
      "color": "whiteCarbon",
    },
        {
      "model": 1,
      "style": "stick",
      "color": "greenCarbon",
    }
        
  ]
    
    out = Molecule3D(reps=reps)
    metrics = gr.JSON(label="Metrics")
    run_time = gr.Textbox(label="Runtime")

    btn.click(predict, inputs=[input_sequence, input_ligand, input_msa, input_protein], outputs=[out,metrics, run_time])

app.launch()