#
# calculation of natural product-likeness as described in:
#
# Natural Product-likeness Score and Its Application for Prioritization of Compound Libraries
# Peter Ertl, Silvio Roggo, and Ansgar Schuffenhauer
# Journal of Chemical Information and Modeling, 48, 68-74 (2008)
# http://pubs.acs.org/doi/abs/10.1021/ci700286x
#
# for the training of this model only openly available data have been used
# ~50,000 natural products collected from various open databases
# ~1 million drug-like molecules from ZINC as a "non-NP background"
#
# peter ertl, august 2015
#


from rdkit import Chem
from rdkit.Chem import rdMolDescriptors
import sys, math, gzip, pickle
import os.path
from collections import namedtuple


def readNPModel(filename=os.path.join(os.path.dirname(__file__), 'publicnp.model.gz')):
  """Reads and returns the scoring model,
  which has to be passed to the scoring functions."""
  print("reading NP model ...", file=sys.stderr)
  fscore = pickle.load(gzip.open(filename))
  print("model in", file=sys.stderr)
  return fscore


def scoreMolWConfidence(mol, fscore):
  """Next to the NP Likeness Score, this function outputs a confidence value
  between 0..1 that descibes how many fragments of the tested molecule
  were found in the model data set (1: all fragments were found).

  Returns namedtuple NPLikeness(nplikeness, confidence)"""

  if mol is None:
    raise ValueError('invalid molecule')
  fp = rdMolDescriptors.GetMorganFingerprint(mol, 2)
  bits = fp.GetNonzeroElements()

  # calculating the score
  score = 0.0
  bits_found = 0
  for bit in bits:
    if bit in fscore:
      bits_found += 1
      score += fscore[bit]

  score /= float(mol.GetNumAtoms())
  confidence = float(bits_found / len(bits))

  # preventing score explosion for exotic molecules
  if score > 4:
    score = 4. + math.log10(score - 4. + 1.)
  elif score < -4:
    score = -4. - math.log10(-4. - score + 1.)
  NPLikeness = namedtuple("NPLikeness", "nplikeness,confidence")
  return NPLikeness(score, confidence)


def scoreMol(mol, fscore):
  """Calculates the Natural Product Likeness of a molecule.

  Returns the score as float in the range -5..5."""
  return scoreMolWConfidence(mol, fscore).nplikeness


def processMols(fscore, suppl):
  print("calculating ...", file=sys.stderr)
  count = {}
  n = 0
  for i, m in enumerate(suppl):
    if m is None:
      continue

    n += 1
    score = "%.3f" % scoreMol(m, fscore)

    smiles = Chem.MolToSmiles(m, True)
    name = m.GetProp('_Name')
    print(smiles + "\t" + name + "\t" + score)

  print("finished, " + str(n) + " molecules processed", file=sys.stderr)


if __name__ == '__main__':

  fscore = readNPModel()  # fills fscore

  suppl = Chem.SmilesMolSupplier(sys.argv[1], smilesColumn=0, nameColumn=1, titleLine=False)
  processMols(fscore, suppl)

#
# Copyright (c) 2015, Novartis Institutes for BioMedical Research Inc.
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