Curie-Web/app/views.py

"""
Flask Documentation:     http://flask.pocoo.org/docs/
Jinja2 Documentation:    http://jinja.pocoo.org/2/documentation/
Werkzeug Documentation:  http://werkzeug.pocoo.org/documentation/
"""
import os
from app import app
from flask import render_template, request, flash, send_file
from werkzeug.utils import secure_filename
from random import choice, shuffle
from string import digits, ascii_lowercase
from pymed import PubMed
from datetime import datetime,date
import json
import subprocess

import mysql.connector as con
from mysql.connector.errors import InterfaceError,DatabaseError



import requests

import logging
import logzero
from logzero import logger
logzero.loglevel(logging.DEBUG)
if app.config['SAVE_LOGS']:
    logFile = app.config['LOG_FOLDER'] + date.today().strftime("%m-%d-%y") + ".log"
    logzero.logfile(logFile, maxBytes=1e6, backupCount=3)

import configparser
misc = configparser.ConfigParser()
misc.read('app/misc.ini')
errors = misc['ERRORS']
AlertSMARTS = misc['ALERT_SMARTS']
AlertDescription = misc['ALERT_DESCRIPTION']

base = os.getcwd()

# Note: that when using Flask-WTF we need to import the Form Class that we created
# in forms.py
from .forms import MyForm, curieForm, statusForm, generateSMILES, PyMedSearch, dockSingleForm, generatePDBQTS

def log(message,logType="INFO"):
    if app.config['LOG']:
        if logType == "INFO":
            logger.info(message)
        elif logType == "DEBUG":
            logger.debug(message)
        elif logType == "EXCEPTION":
            logger.exception(message)
        elif logType == "DANGER":
            logger.error(message)
    return None

def gen_word(N, min_N_dig, min_N_low):
    choose_from = [digits]*min_N_dig + [ascii_lowercase]*min_N_low
    choose_from.extend([digits + ascii_lowercase] * (N-min_N_low-min_N_dig))
    chars = [choice(bet) for bet in choose_from]
    shuffle(chars)
    return ''.join(chars)

def convertToBinaryData(filename):
    # Convert digital data to binary format
    with open(filename, 'rb') as file:
        binaryData = file.read()
    return binaryData

###
# Routing for your application.
###

@app.route('/')
def home():
    """Render website's home page."""
    return render_template('home.html')

@app.route('/About')
def about():
    """Render about page."""
    return render_template('about.html')

@app.route('/Editor')
def editor():
    """Render Molecular Editor"""
    return render_template('molecule_editor.html')

@app.route('/Visualise')
def visualise():
    """Render visualisation page."""
    return render_template('visualise.html')    

@app.route('/Search',methods=['GET','POST'])
def pubmed():
    """Query PubMed"""
    form = PyMedSearch()
    pubmed = PubMed(tool="Curie", email="navanchauhan@gmail.com")

    if request.method == 'POST' and form.validate_on_submit():
        q = form.query.data
        log(form,"DEBUG")
        log(pubmed,"DEBUG")
        results = pubmed.query(q,max_results=100) 
        search = []
        for x in results:
            search.append(x.toDict())

        return render_template('search.html',result=search,form=form)
    
    flash_errors(form)
    return render_template('search.html',form=form)

@app.route('/Compound-Search',methods=['GET','POST'])
def pubchem():
    form = PyMedSearch()
    
    if request.method == 'POST' and form.validate_on_submit():
        q = form.query.data
        response = requests.get('https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/name/%s/property/Fingerprint2D,CanonicalSMILES,IsomericSMILES/JSON' % q.strip())
        if response.status_code == 404:
            return render_template('error.html',code="PC00",description=errors["PC00"])
        search = response.json()["PropertyTable"]["Properties"]
        print(search)
        return render_template('search-pubchem.html',result=search,form=form)
    return render_template('search-pubchem.html',form=form)

@app.route('/Properties',methods=['GET','POST'])
def propalert():
    form = PyMedSearch()

    if request.method == 'POST' and form.validate_on_submit():
        q = form.query.data
        result = []
        perfect = False
        complete = False

        try:
            from rdkit import Chem
        except ImportError:
            return render_template('error.html',code="RD00",description=errors["RD00"])

        if Chem.MolFromSmiles(q.strip()) is None:
            print("invalid smiles")
            return render_template('error.html',code="RD01",description=errors["RD01"])

        for alert in AlertSMARTS:
            print("Checking",alert,AlertSMARTS[alert])
            records = {}
            records['Name'] = alert
            try:
                records['SVG'] = get_svg(q,AlertSMARTS[alert])
            except:
                continue
            records['Description'] = AlertDescription[alert]
            result.append(records)

        prop = get_prop(q)
        print(prop)

        complete = True

        if len(result) == 0:
            perfect = True

        return render_template('mol-characteristics.html',complete=complete,result=result,form=form,perfect=perfect,prop=prop)
    return render_template('mol-characteristics.html',form=form)

@app.route('/Status',methods=['GET','POST'])
def status():
    taskStatusForm = statusForm()

    if request.method == 'POST':
        if taskStatusForm.validate_on_submit():
            jobID = taskStatusForm.jobID.data
            
            try:
                mycon = con.connect(host=app.config['DB_HOST'],user=app.config['DB_USER'],password=app.config['DB_PASSWORD'],port=app.config['DB_PORT'],database=app.config['DB_NAME'])
                mycursor = mycon.cursor()
            except InterfaceError:
                return render_template('error.html',code="DB00",description=errors['DB00'])
            except DatabaseError:
                return render_template('error.html',code="DB02",description=errors['DB02'])
            sqlQuery = 'select id, protein_name, ligand_name, date, description, done, pdb from curieweb where id="%s"' % (jobID)
            mycursor.execute(sqlQuery)
            records = mycursor.fetchall()
            if records == []:
                return render_template('error.html',code="DB01",description=errors['DB01'])
            r = records[0]
            protein_name = r[1]
            ligand_name = r[2]
            date = r[3]
            description = r[4]
            done = r[5]
            if done==1:
                done="Completed"
            elif done==0:
                done="Queued"
            if protein_name == None:
                protein_name = r[6]

            PDFReport = "/static/uploads/reports/" + str(jobID) + ".pdf"
            AndroidModel = "/static/uploads/3DModels/" + str(jobID) + ".gltf"
            iOSModel = "/static/uploads/3DModels/" + str(jobID) + ".usdz"

            uploadsFolder = os.path.join(base,"app/static/uploads/")
            if os.path.exists(os.path.join(uploadsFolder,"reports",str(jobID)+".pdf")):
                reportDone = 'exists'
            else:
                reportDone = False
            if os.path.exists(os.path.join(uploadsFolder,"3DModels",str(jobID)+".gltf")):
                ModelDone = 'exists'
            else:
                ModelDone = False

            return render_template('job_status.html',ID=jobID,pn=protein_name,ln=ligand_name,subDate=date,desc=description,status=done,model=ModelDone,report=reportDone,PDFReport=PDFReport,AndroidModel=AndroidModel,iOSModel=iOSModel)
        flash_errors(taskStatusForm)
    return render_template('job_status_form.html',form=taskStatusForm)
        

@app.route('/PDBQTs',methods=['GET','POST'])
def generate_pdbqts():
    myform = generatePDBQTS()

    if request.method == 'POST':
        if myform.validate_on_submit():
            pdbId = myform.pdb.data
            smiles = myform.smiles.data
            name = myform.name.data
            if (len(pdbId)==0) and (len(smiles)==0):
                log("Nothing Submitted!","WARNING")
                flash("Invalid Submission!",'danger')
            if len(smiles) != 0:
                try:
                    import oddt
                except ImportError:
                    return render_template('error.html',code="OD00",description=errors['OD00'])
                try:
                    mol = oddt.toolkit.readstring('smi', smiles)
                except:
                    return render_template('error.html',code="OD01",description=errors['OD01'])
                try:
                    mol.make3D()
                    mol.calccharges()
                except:
                    return render_template('error.html',code="OD02",description=errors['OD02'])
                from oddt.docking.AutodockVina import write_vina_pdbqt
                
                try:
                    write_vina_pdbqt(mol,'app',flexible=False)
                except:
                    return render_template('error.html',code="OD03",description=errors['OD03'])
                path = ".pdbqt"
                if ".pdbqt" in name:
                    fname = name
                else:
                    fname = name + ".pdbqt"
                return send_file(path,attachment_filename=fname,as_attachment=True)
            if len(pdbId) != 0:
                try:
                    from plip.basic import config
                except ImportError:
                    return render_template('error.html',code="PL00",description=errors['PL00'])
                from plip.exchange.webservices import fetch_pdb
                from plip.structure.preparation import create_folder_if_not_exists, extract_pdbid
                from plip.structure.preparation import tilde_expansion, PDBComplex

                try:
                    pdbfile, pdbid = fetch_pdb(pdbId.lower())
                except:
                    return render_template('error.html',code="PL01",description=errors['PL01'])
                pdbpath = tilde_expansion('%s/%s.pdb' % (config.BASEPATH.rstrip('/'), pdbid))
                create_folder_if_not_exists(config.BASEPATH)
                with open(pdbpath, 'w') as g:
                    g.write(pdbfile)
                try:
                    import oddt
                except:
                    return render_template('error.html',code="OD00",description=errors['OD00'])
                from oddt.docking.AutodockVina import write_vina_pdbqt
                try:
                    receptor = next(oddt.toolkit.readfile("pdb",pdbpath.split("./")[1]))
                    receptor.calccharges()
                except Exception:
                    receptor = next(oddt.toolkits.rdk.readfile("pdb",pdbpath.split("./")[1]))
                    receptor.calccharges()

                try:
                    path = write_vina_pdbqt(receptor,'app',flexible=False)
                except:
                    return render_template('error.html',code="OD03",description=errors['OD03'])
                os.rename(path,"app/.pdbqt")
                path = ".pdbqt"
                fname = pdbId.upper() + ".pdbqt"
                return send_file(path,attachment_filename=fname,as_attachment=True) 
        flash_errors(myform)
    return render_template('pdbqt_form.html',form=myform)
            

tfWorking = 0
if app.config['LSTM']:
    try:
        import tensorflow as tf
        tfWorking = 1
    except Exception as e:
        log(e,"EXCEPTION")
        tfWorking = 0

if tfWorking == 1:
    from lstm_chem.utils.config import process_config
    from lstm_chem.model import LSTMChem
    from lstm_chem.generator import LSTMChemGenerator
    config = process_config("app/prod/config.json")
    modeler = LSTMChem(config, session="generate")
    gen = LSTMChemGenerator(modeler)
    log("Heating up model","INFO")
    gen.sample(1)

@app.route('/Generate', methods=['GET','POST'])
def generate():
    """Generate novel drugs"""
    form = generateSMILES()

    with open("./app/prod/config.json") as config:
        import json
        j = json.loads(config.read())
        log(("Model Name:", j["exp_name"]),"INFO")
    

    if request.method == 'POST' and form.validate_on_submit():
        log(tfWorking,"DEBUG")
        if tfWorking == 0:
            log("Failed to initialise model","DANGER")   
            flash("Failed to initialise the model!","danger")
        else:
            result = gen.sample(form.n.data)
            return render_template('generate.html',expName=j["exp_name"],epochs=j["num_epochs"],optimizer=j["optimizer"].capitalize(), form=form,result=result)

    return render_template('generate.html',expName=j["exp_name"],epochs=j["num_epochs"],optimizer=j["optimizer"].capitalize(), form=form)

@app.route('/Dock-Manual', methods=['GET', 'POST'])
def dock_manual():
    form = curieForm()

    if request.method == 'POST' and form.validate_on_submit():
        log(("Recieved task: ",form.description.data),"DEBUG")
        description = form.description.data
        target = form.target.data
        ligand = form.ligand.data
        cx,cy,cz = str(form.center_x.data), str(form.center_y.data), str(form.center_z.data)
        sx,sy,sz = str(form.size_x.data), str(form.size_y.data), str(form.size_z.data)
        email = form.email.data

        try:
            mycon = con.connect(host=app.config['DB_HOST'],user=app.config['DB_USER'],password=app.config['DB_PASSWORD'],port=app.config['DB_PORT'],database=app.config['DB_NAME'])
            mycursor = mycon.cursor()
        except InterfaceError:
            return render_template("error.html",code="DB00",description=errors['DB00'])
        except DatabaseError:
            return render_template("error.html",code="DB02",description=errors['DB02'])

        import tempfile
        with tempfile.TemporaryDirectory() as directory:
            os.chdir(directory)
            target.save(secure_filename(target.filename))
            ligand.save(secure_filename(ligand.filename))
            buffer = "center_x="+cx+"\ncenter_y="+cy+"\ncenter_z="+cz+"\nsize_x="+sx+"\nsize_y="+sy+"\nsize_z="+sz
            with open("config.txt","w") as f:
                f.write(buffer)
            ligandB = convertToBinaryData(secure_filename(ligand.filename))
            receptor = convertToBinaryData(secure_filename(target.filename))
            config = convertToBinaryData("config.txt")
            ligandName = secure_filename(ligand.filename)
            receptorName = secure_filename(target.filename)
            sqlQuery = "insert into curieweb (id, email, protein, protein_name, ligand_pdbqt, ligand_name,date, description, config) values (%s,%s,%s,%s,%s,%s,CURDATE(),%s,%s) "
            jobID = gen_word(16, 1, 1)
            log(("Submitted JobID: ",jobID),"DEBUG")
            insert_tuple = (jobID,email,receptor,receptorName,ligandB,ligandName,description,config)
            mycursor.execute(sqlQuery,insert_tuple)
            mycon.commit()

        log(("Description",description),"DEBUG")
        print(base)
        cwd = os.path.join(base,"app")

        if app.config['INSTANT_EXEC']:
            subprocess.Popen(['python3', 'dock-manual.py'],cwd=cwd)
        return render_template('display_result.html', filename="OwO", description=description,job=jobID)

    flash_errors(form)
    return render_template('dock_manual.html', form=form)

@app.route('/Dock-Automatic', methods=['GET', 'POST'])
def dock_automatic():
    form = dockSingleForm()

    if request.method == 'POST' and form.validate_on_submit():
        log(("Recieved task: ",form.description.data),"DEBUG")
        description = form.description.data
        pdb = form.pdbID.data
        smile = form.smiles.data
        name = form.name.data
        email = form.email.data

        if len(pdb) != 4:
            return render_template("error.html",code="CW01",description=errors['CW01'])

        try:
            mycon = con.connect(host=app.config['DB_HOST'],user=app.config['DB_USER'],password=app.config['DB_PASSWORD'],port=app.config['DB_PORT'],database=app.config['DB_NAME'])
            mycursor = mycon.cursor()
        except InterfaceError:
            return render_template('error.html',code="DB00",description=errors['DB00'])
        except DatabaseError:
            return render_template("error.html",code="DB02",description=errors['DB02'])

        sqlQuery = "insert into curieweb (id, email, pdb, ligand_smile, ligand_name, date, description) values (%s,%s,%s,%s,%s,CURDATE(),%s) "
        jobID = gen_word(16, 1, 1)

        insert_tuple = (jobID,email,pdb,smile,name,description)
        mycursor.execute(sqlQuery,insert_tuple)
        mycon.commit()

        log(("Description",description),"DEBUG")

        #cwd = os.path.join(os.getcwd(),"app")
        cwd = os.path.join(base,"app")

        if app.config['INSTANT_EXEC']:
            subprocess.Popen(['python3', 'dock-single.py'],cwd=cwd)
        
        return render_template('display_result.html', filename="OwO", description=description,job=jobID)

    flash_errors(form)
    return render_template('dock_automatic.html', form=form)

###
# The functions below should be applicable to all Flask apps.
###

# Flash errors from the form if validation fails
def flash_errors(form):
    for field, errors in form.errors.items():
        for error in errors:
            flash(u"Error in the %s field - %s" % (
                getattr(form, field).label.text,
                error
            ), 'danger')

@app.route('/<file_name>.txt')
def send_text_file(file_name):
    """Send your static text file."""
    file_dot_text = file_name + '.txt'
    return app.send_static_file(file_dot_text)


@app.after_request
def add_header(response):
    """
    Add headers to both force latest IE rendering engine or Chrome Frame,
    and also to cache the rendered page for 10 minutes.
    """
    response.headers['X-UA-Compatible'] = 'IE=Edge,chrome=1'
    response.headers['Cache-Control'] = 'public, max-age=0'
    return response


@app.errorhandler(404)
def page_not_found(error):
    """Custom 404 page."""
    return render_template('404.html'), 404


if __name__ == '__main__':
    app.run(debug=True, host="0.0.0.0", port="8080")

def get_svg(base,pattern):
    try:
        from rdkit.Chem.Draw import rdMolDraw2D
        from rdkit import Chem
    except:
        return None # Need to add logic

    mol = Chem.MolFromSmiles(base)
    patt = Chem.MolFromSmarts(pattern)
    hit_ats = list(mol.GetSubstructMatch(patt))
    hit_bonds = []
    for bond in patt.GetBonds():
        aid1 = hit_ats[bond.GetBeginAtomIdx()]
        aid2 = hit_ats[bond.GetEndAtomIdx()]
        hit_bonds.append(mol.GetBondBetweenAtoms(aid1,aid2).GetIdx())
    d = rdMolDraw2D.MolDraw2DSVG(500, 500)
    rdMolDraw2D.PrepareAndDrawMolecule(d, mol, highlightAtoms=hit_ats, highlightBonds=hit_bonds)
    return d.GetDrawingText().replace("width='500' height='500'","").replace("width='500px' height='500px'","")

def get_prop(base):
    try:
        from rdkit import Chem
        from rdkit.Chem import Crippen
        from rdkit.Chem import Descriptors
        from rdkit.Chem import rdMolDescriptors
        from rdkit.Chem import Lipinski
    except:
        return None # Need to add logic
    result = {}

    mol = Chem.MolFromSmiles(base)
    result["cLogP"] = Crippen.MolLogP(mol)
    result["Molecular Weight"] = Descriptors.MolWt(mol)
    result["TPSA"] = rdMolDescriptors.CalcTPSA(mol)
    result["Hydrogen Bond Acceptors"] = Lipinski.NumHAcceptors(mol)
    result["Hydrogen Bond Donors"] = Lipinski.NumHDonors(mol)
    result["Rotable Bonds"] = Lipinski.NumRotatableBonds(mol)
    result["Fraction SP3"]  = Lipinski.FractionCSP3(mol)


    return result