Hi Nils and Axel, Thank you very much for your response.
I am trying to develop a de-novo drug design framework that uses fragments as building blocks to assemble a molecule inside a target protein active site. The algorithm that I am using assembles fragments into molecules such that the resulting molecules satisfy a certain properties. However, the properties have to be additive, like for example: the molecular weight or polar surface area, where the sum of the fragments is equal to that of the whole molecule. I have incorporated a number of such fragment-based additive properties, and when trying to incorporate the SA_score, I realised that it didn't work. -- Best, Ganesh On Wed, Apr 1, 2020 at 11:47 AM Nils Weskamp <nils.wesk...@gmail.com> wrote: > Hi Ganesh, > > I would like to challenge your premise. Why do you think that synthetic > accessibility should add up like that? > > Theoretically, I would expect that the combination of A,B and C to ABC > will require some synthetic effort - so should be SA(A) + SA(B) + SA(C) < > SA(ABC). > > Technically, the combination of the three fragments will change the > properties and environment of at least some atoms in the molecule, so that > should have an influence on the result. I suspect it will be difficult to > define a score with the desired properties without making use of the > fragmentation scheme you are using. > > Best regards, > Nils > > > On Wed, Apr 1, 2020 at 12:36 PM Ganesh Shahane <ganesh7shah...@gmail.com> > wrote: > >> Hi Axel, >> >> Thank you for your response. >> >> Yes, I tried to implement the aforementioned script. It works very well >> on whole molecules. >> >> However, I am trying to implement the script on fragments. For example, >> if I have fragments: A, B and C that makes up a whole molecule "ABC", then >> the sum of SA scores of the fragments should be equal to SA score of the >> whole molecule. >> >> Right now, the summation doesn't add up. >> >> I was wondering if there is a correction that needs to be made to the sum >> of SA scores such that it is equal to the SA score of the whole molecule. >> >> -- >> Best, >> Ganesh >> >> >> On Mon, Mar 30, 2020 at 4:30 PM Axel Pahl <axelp...@gmx.de> wrote: >> >>> Hi Ganesh, >>> >>> are you aware that the SA Score IS implemented in RDKit: >>> >>> https://github.com/rdkit/rdkit/tree/master/Contrib/SA_Score >>> >>> Kind regards, >>> Axel >>> >>> >>> >>> On 30.03.20 16:55, Ganesh Shahane wrote: >>> >>> Dear RDKitters, >>> >>> I am trying a to find a way to implement the SA score as a sum of >>> fragments contributions from this paper: >>> >>> Ertl, Peter, and Ansgar Schuffenhauer. 2009. “Estimation of Synthetic >>> Accessibility Score of Drug-like Molecules Based on Molecular Complexity >>> and Fragment Contributions.” *Journal of Cheminformatics* 1 (1): 8. >>> >>> For example, if I have three different fragments: A, B and C and their >>> respective SA scores, then the SA score of molecule "A+B+C" should be the >>> sum of all three fragment SA scores. >>> >>> In practice though, the fragment SA scores do not add up. >>> >>> I was wondering if anyone across the cheminformatics community has >>> successfully implemented this or a similar strategy? >>> >>> -- >>> Best, >>> Ganesh >>> >>> >>> _______________________________________________ >>> Rdkit-discuss mailing >>> listRdkit-discuss@lists.sourceforge.nethttps://lists.sourceforge.net/lists/listinfo/rdkit-discuss >>> >>> _______________________________________________ >>> Rdkit-discuss mailing list >>> Rdkit-discuss@lists.sourceforge.net >>> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss >>> >> _______________________________________________ >> Rdkit-discuss mailing list >> Rdkit-discuss@lists.sourceforge.net >> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss >> >
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