B 3RcvPM@sDddlmZddlmZddlmZddlmZmZddlZddl Z ddl m Z Gdd d e Zded d Zed ddddddddddddddddddd d!d"d#d$d%d&d'd(d)d*d+d,d-d.d/d0d1d2d3d4d5d6d7d8d9d:d;dd?d@dAdBdCdDdEdFdGdHdIdJdKdLdMdNdOdPdQdRdSdTdUdVdWdXgLZdfdYdZZdgd[d\Zd]d^Zdhd_d`ZdadbZdcddZdS)i)Chem)AllChem) rdqueries) defaultdictCounterN)utilsc@sbeZdZdddddddgZdd Zd d ZdddZddZddZddZ ddZ dddZ dS)MoleculeDetailsdetailFP scaffoldFPbitInfoDetailFPbitInfoScaffoldFP reactivityZ bitReactivitymoleculecCs|d|}t||}dg|}xt|D]\}}g}|||| || || | d|| | d|| ||tt|d@||<qt|D].\}}g}||tt|d@||<q W|S)Nrl)rrrrrrr)rrrrr r!r"r#r#r$_atomScaffoldInvariantEs z&MoleculeDetails._atomScaffoldInvariantTrcCstj|||||dS)N)rradiusr useBondTypesZbitInfo)rZGetMorganFingerprint)rrZ invariantZbitinfor(r'r#r#r$ _createFPNszMoleculeDetails._createFPcCs |dkS)N)rr)r)rr!r#r#r$ _isHeteroAtomQszMoleculeDetails._isHeteroAtomcCsB|dkrdS|rdSx |D]}|dkr&dSq&WdS)NrFTg?)rrGetBondsGetBondTypeAsDouble)rr!br#r#r$_isSp3OrAromaticCarbonTs  z&MoleculeDetails._isSp3OrAromaticCarboncCs||s&t|dkr*|dkr*dSd}|}||sL|dkrT|d7}|rn|rv|d7}n|d7}|r|d7}x|D]~}| |}| dkr|d7}|dkr|d7}||r|d7}| dkr| dkr|d7}q| dkr|d7}qW|S)Nrrg?g?)) .2) r.lenZ GetNeighborsZGetFormalCharger+r*rrrZ GetOtherAtomr,r)rr!rr-ZboZnir#r#r$_calcReactivityAtom^s2&         z#MoleculeDetails._calcReactivityAtomcsfdd|D}|S)Ncsg|]}|qSr#)r8).0r!)rr#r$ sz;MoleculeDetails._calcReactivityMolecule..)r)rrreactivityAtomsr#)rr$_calcReactivityMoleculesz'MoleculeDetails._calcReactivityMoleculercCsx||_i|_|||||j|_i|_|j||||jdd|_||}t |}t |t krn|d9}||_ dS)NF)r(g?)rr r)r%r r r&r r<sumrZ MolToSmilesfrequentReagentsr)rrverboser;rr#r#r$__init__s zMoleculeDetails.__init__N)Tr)r) __name__ __module__ __qualname__ __slots__r%r&r)r*r.r8r<r@r#r#r#r$r /s  (r Fc Cs"|r tdd}||}tt|}|dkr8td|tt|}|dkrXtd|tt|}|dkrxtd|tt|} |dkrtd| d} d} |dk rt||\} } |dkrtd | d ||} | |} t| | | d}|d krtd |d | d | | d | d ||| | gS)Nz--- _calcScore ---rr/z num RBits: z num PBits: znum UnmappedPBits: znum UnmappedRBits: znum UnmappedPAtoms: rzscore: (,))printfloatrZgetNumPositiveCountsZgetNumNegativeCounts getNumPositiveBitCountsOfRadius0max)Z reactantFPZ productFP bitInfoProdoutputscoreZdFPZnumRBitsZnumPBitsZnumUnmappedPBitsZnumUnmappedRBitsnumUnmappedPAtomsbitsUnmappedPAtomsZratioMappedPBitsZratioUnmappedRBitsr#r#r$ _calcScores8       rRz CCN(CC)CCz[Li+]z[Na+]zO=C(O)CC(O)(CC(=O)O)C(=O)Oz O=S(=O)(O)Oz CN1CCCC1=OzCCN(C(C)C)C(C)CZc1ccncc1z[K]z CC(C)(C)OZCCOzCc1ccc(S(=O)(=O)O)cc1z ClC(Cl)(Cl)Clz[Na]z CC(C)(C)[O-]z O=C([O-])OZCOCCOCz[NH4+]z CC(C)OC(C)Cz O=C([O-])[O-]z CC(=O)OC(C)=OzO=C=Oz[Cl-]zc1ccc(P(c2ccccc2)c2ccccc2)cc1z[H-]zN#NZ CN1CCOCC1ZC1COCCO1Zc1ccccc1z[Cs+]z[K+]z[OH-]ZCCCCCCZCCCCCzCN(C)C=OzC[O-]Z Cc1ccccc1zC1CCC2=NCCCN2CC1ZCOZCCCCOzO=C(O)C(F)(F)FzO=P([O-])([O-])[O-]z CCOC(C)=Oz[Mg+2]ZC1CCCCC1ONZIIzO=COz CC(=O)N(C)CzCC(=O)OZCCOCCzCC(C)Oz C[Si](C)(C)ClZ Cc1ccccc1CzCC(C)=Oz CS(=O)(=O)Oz CN(C)c1ccncc1ZClZClCCClz O=S(Cl)Clz ClC(Cl)Clz[Li]CCCCz[Pd]z[H][H]z[Br-]zCS(C)=Oz COC(C)(C)CzO=S(=O)([O-])[O-]zCC(Cl)Clz CC(=O)[O-]zCCCC[N+](CCCC)(CCCC)CCCCZClCClzCC#NZC1CCOC1ZCCCCCCCcs|r tdg}t}xtd|dD]}xtt||D]~}g}xb|D]Z}|ds|dj} | dkr||dj|fqL|dkrLtd|qLW||kr>||q>Wq(Wd} d} gg} t dd|D} t dd|D}d}x|D]}||j7}qWi}i}x&|D]}| |j | |j q*Wt ||\}}t| t|||gg}xr|D]h}t|dkrqt|dddf}|d |ks||d krԐq|dkrtd |t fd d|D}t fd d|D}t|| ||d}t||||d}|d|d}|dkrtd|td|d|dtd|d|d|d|d|| kr||} |d} | dd=|dd=| dd|D||d|d|d|dg|dkrtd| td| |ddkr2|dd kr2| |fSt|dkrt|dkr|dddkr|dddkr| |fSnnt|| dkr|dkr| dd|D||d|d|d|dg|dkrtdtd| qW| |fS)Nz--- _getBestCombination ---rrzFrequent reagent found: cSsg|] }|jqSr#)r )r9r r#r#r$r:sz'_getBestCombination..cSsg|] }|jqSr#)r )r9r r#r#r$r:srg?z Combination: csg|]}|ddjqS)rr)r )r9r )rfpsr#r$r:scsg|]}|ddjqS)rr)r )r9r )rVr#r$r:s)rMrNz >>>> score: z >>>> scores (detail, scaffold): z">>>> num unmapped productFP bits: r/cSsg|] }|dqS)rr#)r9r r#r#r$r:srEz >> maxScore: z >> Final reactants: gH.?gHz>gcSsg|] }|dqS)rr#)r9r r#r#r$r:"sz >> Added alternative result)rIr7range itertools combinationsrrrrZ getSumFpsupdater r rKZGetNonzeroElementsnparrayr=rRabs)rVpfpsrNZtests numReactantsr xtempjZnumAtmsZmaxScoreZmaxDetailScoreZ finalReactsZproductsDetailFPZproductsScaffoldFPZnumProductAtomsZproductsDetailFPBitInfoZproductsScaffoldFPBitInforPrQZfinalNumUnmappedProdAtomsZtestZnumReactantAtomsZreactantsDetailFPZreactantsScaffoldFPZ detailFPScoreZscaffoldFPScorerOr#)rVr$_getBestCombinations              "   $ " rcc st|r tdt|s|Sg}t}x4t||D]$\}}|||ddkr2tt|t|} t| fdddd} g} xn|dD]b\} } xXtt|D]H} | || jkr|| j| d}| || j |d g| qWqWt | } |dkr t| d d | D}d}d}g}x | D]}|dkrbtd ||jt|j d}x8|D]0\}}t|j || |krl|d7}qlW|dkrtd |td |||kr|}|jt|j }|g}n@|r0||kr0|jt|j |kr0|}|||dkr.td|q.W|d |q2W|dkrptd||S)Nz%--- _findMissingReactiveReactants ---rrcs|jt|jS)N)rrJrr)r`)rVr#r$:z/_findMissingReactiveReactants..T)keyreverserEcSsg|]}t||fqSr#)rZAtomNumEqualsQueryAtom)r9r!r#r#r$r:Gsz1_findMissingReactiveReactants..z >> Reactantz Max reactivityz Max fulfilled queriesz Added reactantsz >> Final 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