#!/usr/bin/env python3
# (C) 2017 OpenEye Scientific Software Inc. All rights reserved.
#
# TERMS FOR USE OF SAMPLE CODE The software below ("Sample Code") is
# provided to current licensees or subscribers of OpenEye products or
# SaaS offerings (each a "Customer").
# Customer is hereby permitted to use, copy, and modify the Sample Code,
# subject to these terms. OpenEye claims no rights to Customer's
# modifications. Modification of Sample Code is at Customer's sole and
# exclusive risk. Sample Code may require Customer to have a then
# current license or subscription to the applicable OpenEye offering.
# THE SAMPLE CODE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
# EXPRESS OR IMPLIED.  OPENEYE DISCLAIMS ALL WARRANTIES, INCLUDING, BUT
# NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A
# PARTICULAR PURPOSE AND NONINFRINGEMENT. In no event shall OpenEye be
# liable for any damages or liability in connection with the Sample Code
# or its use.

#############################################################################
# Enumerates connected fragment combinations
#############################################################################

import sys
from itertools import combinations
from openeye import oechem
from openeye import oemedchem


def main(argv=[__name__]):

    itf = oechem.OEInterface(InterfaceData)

    if not oechem.OEParseCommandLine(itf, argv):
        return 1

    iname = itf.GetString("-in")
    oname = itf.GetString("-out")

    # check input/output files

    ifs = oechem.oemolistream()
    if not ifs.open(iname):
        oechem.OEThrow.Fatal("Cannot open input file!")

    ofs = oechem.oemolostream()
    if not ofs.open(oname):
        oechem.OEThrow.Fatal("Cannot open output file!")

    # read a molecule

    mol = oechem.OEGraphMol()
    if not oechem.OEReadMolecule(ifs, mol):
        oechem.OEThrow.Fatal("Cannot read input file!")

    # initialize fragmentation function

    fragfunc = GetFragmentationFunction(itf)

    frags = [f for f in fragfunc(mol)]
    oechem.OEThrow.Info("%d number of fragments generated" % len(frags))

    # generate fragment combinations

    fragcombs = GetFragmentCombinations(mol, frags)
    oechem.OEThrow.Info("%d number of fragment combinations generated" % len(fragcombs))

    for frag in fragcombs:
        oechem.OEWriteMolecule(ofs, frag)

    return 0


def IsAdjacentAtomBondSets(fragA, fragB):

    for atomA in fragA.GetAtoms():
        for atomB in fragB.GetAtoms():
            if atomA.GetBond(atomB) is not None:
                return True
    return False


def IsAdjacentAtomBondSetCombination(fraglist):

    parts = [0] * len(fraglist)
    nrparts = 0

    for idx, frag in enumerate(fraglist):
        if parts[idx] != 0:
            continue

        nrparts += 1
        parts[idx] = nrparts
        TraverseFragments(frag, fraglist, parts, nrparts)

    return (nrparts == 1)


def TraverseFragments(actfrag, fraglist, parts, nrparts):

    for idx, frag in enumerate(fraglist):
        if parts[idx] != 0:
            continue

        if not IsAdjacentAtomBondSets(actfrag, frag):
            continue

        parts[idx] = nrparts
        TraverseFragments(frag, fraglist, parts, nrparts)


def CombineAndConnectAtomBondSets(fraglist):

    # combine atom and bond sets

    combined = oechem.OEAtomBondSet()
    for frag in fraglist:
        for atom in frag.GetAtoms():
            combined.AddAtom(atom)
        for bond in frag.GetBonds():
            combined.AddBond(bond)

    # add connecting bonds

    for atomA in combined.GetAtoms():
        for atomB in combined.GetAtoms():
            if atomA.GetIdx() < atomB.GetIdx():
                continue

            bond = atomA.GetBond(atomB)
            if bond is None:
                continue
            if combined.HasBond(bond):
                continue

            combined.AddBond(bond)

    return combined


def GetFragmentAtomBondSetCombinations(mol, fraglist):

    fragcombs = []

    nrfrags = len(fraglist)
    for n in range(2, nrfrags):

        for fragcomb in combinations(fraglist, n):

            if IsAdjacentAtomBondSetCombination(fragcomb):

                frag = CombineAndConnectAtomBondSets(fragcomb)
                fragcombs.append(frag)

    return fragcombs


def GetFragmentCombinations(mol, fraglist):

    fragments = []
    fragcombs = GetFragmentAtomBondSetCombinations(mol, fraglist)

    for f in fragcombs:

        fragatompred = oechem.OEIsAtomMember(f.GetAtoms())
        fragbondpred = oechem.OEIsBondMember(f.GetBonds())

        fragment = oechem.OEGraphMol()
        adjustHCount = True
        oechem.OESubsetMol(fragment, mol, fragatompred, fragbondpred, adjustHCount)
        fragments.append(fragment)

    return fragments


def GetFragmentationFunction(itf):

    fstring = itf.GetString("-fragtype")
    if fstring == "funcgroup":
        return oemedchem.OEGetFuncGroupFragments
    if fstring == "ring-chain":
        return oemedchem.OEGetRingChainFragments
    return oemedchem.OEGetRingLinkerSideChainFragments


#############################################################################
# INTERFACE
#############################################################################

InterfaceData = '''
!CATEGORY "input/output options"
    !PARAMETER -in
      !ALIAS -i
      !TYPE string
      !REQUIRED true
      !KEYLESS 1
      !VISIBILITY simple
      !BRIEF Input filename
    !END

    !PARAMETER -out
      !ALIAS -o
      !TYPE string
      !REQUIRED true
      !KEYLESS 2
      !VISIBILITY simple
      !BRIEF Output filename
    !END
!END

!CATEGORY "fragmentation options"
    !PARAMETER -fragtype
      !ALIAS -ftype
      !TYPE string
      !REQUIRED false
      !KEYLESS 3
      !DEFAULT funcgroup
      !LEGAL_VALUE funcgroup
      !LEGAL_VALUE ring-chain
      !LEGAL_VALUE ring-linker-sidechain
      !VISIBILITY simple
      !BRIEF Fragmentation type
    !END
!END
'''


if __name__ == "__main__":
    sys.exit(main(sys.argv))