Re: [Rdkit-discuss] Exhaustive Library Enumeration

[Andy J. <and...@gm...>]

Hi Christos,

Many thanks for the reply. I hadn't appreciated that the presence of a
single invalid reagent would bring the entire thing crashing down, rather
than issuing a warning/error and moving onto other molecules in the set.
Good to know, and I'll have to be less lazy in my code ;-)

Best,
Andy

On Wed, Jan 17, 2018 at 1:56 PM, Christos Kannas <chr...@gm...>
wrote:

> Hi Andy,
>
> The reason that your code breaks is that the second product of the third
> iteration ( 'NCCCCN(Cc1ccccc1)(Cc1ccccc1)Cc1ccccc1') is not a valid
> molecule.
> And when calling Chem.MolFromSmiles( 'NCCCCN(Cc1ccccc1)(Cc1ccccc1)Cc
> 1ccccc1') it creates a None object.
> So you have to filter out the molecules that are not valid.
>
> See this Jupyter Notebook
> <https://gist.github.com/CKannas/11bb9bcaa9435dd18a0bb969501219b2> at
> cell 5 the 1st line in the while loop.
>
> Best,
>
> Christos
>
> Christos Kannas
>
> Chem[o]informatics Researcher & Software Developer
>
> [image: View Christos Kannas's profile on LinkedIn]
> <http://cy.linkedin.com/in/christoskannas>
>
> On 17 January 2018 at 18:16, Andy Jennings <and...@gm...>
> wrote:
>
>> Hi RDKitters,
>>
>> I have a question and an observation on the topic of library enumeration.
>>
>> First, the question: is there a call within RDKit to trigger the
>> exhaustive reaction of reagents? For example, if I have two reagents - a
>> primary amine and an akyl chloride - can I tell RDKit to enumerate the
>> reaction as though there were an excess of each reagent? In my case here
>> the reaction would continue until the alkylation can no longer occur
>> because there are no more valences available on the amine and I would
>> either be tri-alkylated for a neutral product or quat-alkylated for a
>> positively charged product
>> e.g. CCN + RCl -> CCN(R)(R)R or CC[N+](R)(R)(R)R
>>
>> This brings me to my observation. When I try to attempt exactly this by
>> repeatedly exposing the product to the reagent again I am able to drive it
>> to exhaustion *in some cases*.
>>
>> For example, in the example above where RCl is benzyl chloride and my
>> smirks is:
>> [#7:1].[#6:2][Cl:3]>>[#6:2][#7:1].[Cl:3]'
>> I do drive the final product to be exclusively the tri-akylated amine.
>> Success.
>>
>> However, when I attempt the same thing with an amine with more than one
>> reactive nitrogen (e.g. NCCCCN) I don't get a single product with 6
>> alkylations, I get two unique product each with three alkylations. One
>> product has two alkylations on the first nitrogen and one on the second,
>> the other product has three alkylations on the first nitrogen and none on
>> the second. Attempting to drive the reaction once again leads to a
>> 'reaction called with None reactants' ValueError. My dreadful code is below
>> and the output is
>> Reaction 1: ['NCCCCNCc1ccccc1']
>> Reaction 2: ['NCCCCN(Cc1ccccc1)Cc1ccccc1', 'c1ccc(CNCCCCNCc2ccccc2)cc1']
>> Reaction 3: ['c1ccc(CNCCCCN(Cc2ccccc2)Cc2ccccc2)cc1',
>> 'NCCCCN(Cc1ccccc1)(Cc1ccccc1)Cc1ccccc1']
>> Reaction 4: ValueError
>>
>> Any pointers would be great, as would any pre-existing library
>> enumeration code. The examples I've found shipped with RDKit don't appear
>> to allow me to name the products using a combination of the reagent names
>> (useful for tracking library content).
>>
>> Best,
>> Andy
>>
>> #### Code snippet ####
>>
>> amine = Chem.MolFromSmiles('NCCCCN')
>> acyl = Chem.MolFromSmiles('c1ccccc1CCl')
>> rxn = AllChem.ReactionFromSmarts('[#7:1].[#6:2][Cl:3]>>[#6:2][#7:1
>> ].[Cl:3]')
>>
>> # First reaction
>> reactantListMols = [amine,acyl]
>> prods = AllChem.EnumerateLibraryFromReaction(rxn,[reactantListMols,r
>> eactantListMols])
>> prods = list(prods)
>> smis = list(set([Chem.MolToSmiles(x[0],isomericSmiles=True) for x in
>> prods]))
>> print smis
>> # ['NCCCCNCc1ccccc1']
>>
>> # Now repeat until doom
>> for i in range(0,10):
>>     oldproducts = [Chem.MolFromSmiles(x) for x in smis]
>>     reactantListMols = oldproducts + [acyl]
>>     prods = AllChem.EnumerateLibraryFromReaction(rxn,[reactantListMols,r
>> eactantListMols])
>>     prods = list(prods)
>>     smis = list(set([Chem.MolToSmiles(x[0],isomericSmiles=True) for x in
>> prods]))
>>     print smis
>>
>> #### End Code ####
>>
>>
>>
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