B 3RcvF@sdZddlZddlZddlZddlZddlmZGdddZGdddZGdd d Z Gd d d Z Gd d d Z ddZ ddZ ddZedkredS)a Glare Algorithm Some nomenclature: GLARE: A New Approach for Filtering Large Reagent Lists in Combinatorial Library Design Using Product Properties Jean-Francois Truchon* and Christopher I. Bayly http://pubs.acs.org/doi/pdf/10.1021/ci0504871 A Libary is made of RGroups RGroups are a collection of sidechains (the paper uses Fragments) that can populate the rgroup position. We desire to optimize the Library so that we have a good chance of making the products in the desired property range. Example From the testing code, using Fake data: r1 = RGroups(makeFakeSidechains("aldehydes", num=1000)) r2 = RGroups(makeFakeSidechains("boronic_acids", num=1500)) lib = Library([r1,r2]) props = [ Property("mw", propIdx=0, minValue=0, maxValue=500), Property("alogp", propIdx=1, minValue=-2.4, maxValue=5), Property("tpsa", propIdx=2, minValue=0, maxValue=90) ] glare = Glare() # optimize the library... glare.optimize(lib, props) for reactant_idx, rgroup in enumerate(lib.rgroups): print(f"Reactants for reactant {reactant_idx}") for reactant in rgroup.sidechhains: print(reactant.name) N)reducec@seZdZdddZddZdS)PropertycCs"||_||_||_||_||_dS)aname, propIdx, minValue, maxValue, scaffoldoffset -> initial a Property name is the name of the property. propIdx: the index of the property in the property vector minValue: the minimum acceptable value for the property maxValue: the maximum acceptable value for the property scaffoldoffset: any offset from the reaction scaffold (defaults to 0) N)namepropIdxminValuemaxValueoffset)selfrrrrZscaffoldoffsetr "share/RDKit/Contrib/Glare/glare.py__init__,s zProperty.__init__cCsD|j}|j}x|D]}||j|7}qW|j|ko>|jkSS)asidechains -> Evaluate a list of sidechains to see if they pass the property values. Each sidechain must have a property vector e.g. (s.props for s in sidechains) which is a vector of values where s.props[propIdx] is the property being inspected )r rpropsrr)r sidechainsproductrsr r r evaluate;s  zProperty.evaluateN)r)__name__ __module__ __qualname__r rr r r r r+s rc@s2eZdZdZd ddZddZddZd d Zd S) SidechainzHolds the name (identifier) and property list for the given sidechain/fragment. Properties are assumed to be numerical valuesrcKs"||_||_||_d|_||_dS)awname, props, goodCount=0 -> initialize a Sidechain initialize a sidechain. name: the unique name for the sidechain props: the property vector (see Properties class for details) goodCount: the number of times this reagent belongs to a good product, where good is a product that is in the desired property space. FN)rr good_countZdropped extra_data)r rrZ goodCountrr r r r Ms zSidechain.__init__cCs|jS)N)r)r r r r data\szSidechain.datacCsd|j|j|j|jfS)Nz$Sidechain %s(%s, goodCount=%s, **%r))rrrr)r r r r __str___szSidechain.__str__cCsd|j|j|j|jfS)NzSidechain(%r, %r, %s, **%r))rrrr)r r r r __repr__bszSidechain.__repr__N)r)rrr__doc__r rrrr r r r rIs  rc@sHeZdZdZddZddZddZdd Zd d Zd d Z ddZ dS)RGroupsz5Holds a collection of sidechains for the given RGroupcCs||_g|_t||_dS)zSidechains -> RGroups sidechains: the list of Sidechains that make up the potential sidechains at this rgroup positionN)rrejectedlen initial_size)r rr r r r gszRGroups.__init__cCs t|jS)z)Returns the number of possible sidechains)rr)r r r r countpsz RGroups.countcCs&t|jx|jD] }d|_qWdS)z>Randomly shuffles the sidechains and reset the goodness countsrN)randomZshufflerr)r rr r r randomizets  zRGroups.randomizecCst|jt|jS)z-> return the current effectiveness of this collection effectiveness is the number of items left divided by the initial amount)rrfloatr )r r r r effectivenesszszRGroups.effectivenesscCstttt|j|S)zvnum_chunks -> return the number of sidechains in each chunk if the sidechains are split into num_chunks chunks)intmathZceilr$rr)r num_chunksr r r chunk_sizeszRGroups.chunk_sizecCsH|dkr||ks td||f||}t|j|||d|S)zcchunk_idx, num)chunks -> RGroups return the chunk_idxth chunk given num_chunks total chunksrz%s %s)AssertionErrorr)rr)r chunk_idxr(nr r r chunks  z RGroups.chunkcCsxd|krdks"ntd||jjddddtt|j|d}|j|j|d 7_|jd ||_d S) zfractionToKeep -> Sort the sidechains from the most often found if good products to the least, and keep the best fractionToKeep percentagerg?zfractionToKeep: %scSs|jS)N)r)xr r r zRGroups.prune..T)keyreverseg?N)r+rsortr&rr)r fractionToKeepZfragment_indexr r r prunes "z RGroups.pruneN) rrrrr r!r#r%r)r.r6r r r r res  rc@sHeZdZdZddZddZddZdd Zd d Zd d Z ddZ dS)LibraryzQA library is a collection of RGroups that need to be combinitorially combinedcCs ||_dS)zrgroups -> Initialize the Library. rgroups: the list of possible RGroups that is combinitorially combined to make the libraryN)rgroups)r r8r r r r szLibrary.__init__cCs&x |jD]}t|jdkrdSqWdS)z4If we have an empty set for any rgroup, return FalserFT)r8rr)r rgr r r isValids zLibrary.isValidcCsx|jD] }|qWdS)z%randomize the order of the sidechainsN)r8r#)r r9r r r r#s zLibrary.randomizecsfddt|jD}|jdddd}g}x2|ddD]"\}}|||||f|}q>W|d\}}|||f|d d|D}|S) ztotal_num_partitions -> [num_fragments/partition for rgroup1, num_fragments/partition for rgroup2] return the number of sidechains in a partition for each rgroupcs&g|]\}}|t|dfqS)r*)maxr!).0libIdxr9)total_num_partitions_per_rgroupr r sz5Library.getSidechainsPerPartition..cSs|dS)Nr*r )Zszr r r r0r1z3Library.getSidechainsPerPartition..)r2r*NcSsg|] \}}|qSr r )r<r=sizer r r r?s) enumerater8r4append)r r>ZsizesZ last_sizeZ opt_sizesr=Z current_sizeresr )r>r getSidechainsPerPartitions  z!Library.getSidechainsPerPartitioncCs||}t|}g}x:t|D].}g}x|D]}|||q.W||q Wg}xrt|D]f\} }g} g} x:t|D].\} } |j| }|| }| |j| |dqzWt| }|r`||q`W|S)znum_partitions -> [Library(..), Library(...)] Return new libraries that are chunks of this one. These are the libraries that get sampled to see of sidechains participate in good products. )r,r() rEr;rangerCrBr8r.r7r:)r Znum_partitionsZ partitionsZ max_subsetsZenumeration_indicesi combinationsrAZ library_setsZ subset_indexZlibsZpartitioned_rgroupsZ lib_indexZ libpart_indexlibr(r r r r.s*    z Library.chunkcCs.d}x|jD]}||7}q W|t|jS)z8-> returns the average effectiveness of this library setg)r8r%r)r sumr9r r r r%s zLibrary.effectivenessc Csdd|jD}d}d}x`ttj|D]N\}}xD|D]}||s6|d7}Pq6W|d7}x|D]}|jd7_q`Wq(W||dfS)zprops -> num_good_enumerations, total_enumerations props: a list of Property evaluators for the fragments. returns the number of good enumerations and the total number of enumerations for this LibrarycSsg|] }|jqSr )r)r<r9r r r r?sz$Library.evaluate..rr*)r8rB itertoolsrrr) r rZfragsgoodZbadrGZfragpZ sidechainr r r rs   zLibrary.evaluateN) rrrrr r:r#rEr.r%rr r r r r7s"r7c@s"eZdZdZd ddZd d ZdS) GlareaGlare Algorithm. Implementation of GLARE: A New Approach for Filtering Large Reagent Lists in Combinatorial Library Design Using Product Properties Jean-Francois Truchon* and Christopher I. Bayly http://pubs.acs.org/doi/pdf/10.1021/ci0504871 Usage: # somehow make sidechains1/2 with props [mw, alogp, tpsa] r1 = RGroups(sidechains1) r2 = RGroups(sidechains2) lib = Library([r1, r2]) props = [ Property("mw", 0, 0, 500), Property("alogp", 1, -2.4, 5), Property("tpsa", 2, 0, 90) ] glare = Glare() glare.optimize(lib, props) ffffff?d@NcCs<||_|_||_||_|dk r,|d|_n||_||_dS)NgY@)Z fractionGooddesiredFinalGoodness maxIterations rgroupScaleinitialFraction numPartitions)r rSrTrUrVrWr r r r &s  zGlare.__init__cCsTtdtd|jdtd|j|jdks<|jdkrFtdntd|jdtd d d d |jDttjd d |jDfd}|j}xt d|j dD]}x|jD] }| qWd}}| |j} x2t | D]&\} } | |\} } || 7}|| 7}qW||7}||}|dkr2d}n|dkrt|}|jdk rX|j}}ntd||dd}}n>t||dkrd}nd||||||}td|}ttdd |jD}xn|jD]d}d}|jdk rt|j}d}dt|j ||d}||}d||}|d|qWtd|td|dtd|td|td|d|std|jtd|jtd|jdkrtd ntd!|jtd d d"d |jDttjd#d |jDftd$|d|r*|dkr*dSt||jd%ksH||jkrdSqWdS)&alibrary, props Given a Library and the list of Propery evaluators, optimize the library. The library is modified in place by removing building blocks (sidechains) that are not likely to pass the property criteria. z"------- PARAMETERS: --------------zGOOODNESS THRESHOLD : %s%%rPzMIN PARTITION SIZE : %sNg+?z$INITIAL FRACTION TO KEEP : AUTOMATICzINITIAL FRACTION TO KEEP : %s%%zActual SIZE : %s = %sz x cSsg|]}tt|jqSr )strrr)r<r9r r r r?Gsz"Glare.optimize..cSsg|]}t|jqSr )rr)r<r9r r r r?Hsgr*g-q=gg333333?g?g-C6?g?cSsg|]}t|jqSr )rr)r<r9r r r r?sg?z4-------------- ITERATION : %s ----------------------zGOODNESS : %s%%zNUMBER EVAL : %szCUMUL EVAL : %szKEPT IN STEP : %s%%gY@zGOODNESS THRESHOLD : %szINITIAL FRACTION TO KEEP : Z AUTOMATICz%s%%cSsg|]}tt|jqSr )rXrr)r<r9r r r r?scSsg|]}t|jqSr )rr)r<r9r r r r?szEFFECTIVENESS : %s%%gMbP?)printrSrWrVjoinr8roperatormulrFrTr#r.rBrminabsr$r;rUrrr'Zexpr6r5r%)r ZlibraryrZ running_totalZGtZ iterationr9rLZtotalZ chunked_libsZlibidxr.gtZGiZfractionZG0ZK0ZKiZmax_sizeZscaleZ numSidechainsZnumerZdenomZfraction_to_rejectr r r optimize6s                       zGlare.optimize)rOrPrQNrR)rrrrr rar r r r rNs rNcCs.tdd}tdd}tdd}|||gS)N iir)r"Zrandint)mwalogptpsar r r makeFakePropss   rgcCs8g}x.t|D]"}|t|dt|tqW|S)N_)rFrCrrXrg)rIZnumrDrGr r r makeFakeSidechainss"ricCsttdd}ttdd}t||g}tdddddtd d d d d tdddddg}t}|||x>t|jD]0\}}td|x|j D]}t|j qWqtWdS)NZ aldehydesiZ boronic_acidsirdrigiql@rer*g333333g j@rfZg8@zReactants for reactant ) rrir7rrNrarBr8rYrr)abrIrZglareZ reactant_idxZrgroupZreactantr r r testGlares   ro__main__)rr"r[rKr' functoolsrrrrr7rNrgrirorr r r r &s  7s