Hi Ganesh, To delve a bit deeper into this, if I recall correctly, SA score is calculated based on both:
1. The prevalence of your molecule’s chemical motifs in a virtual library of synthesizable compounds. 2. A set of logarithmic formulas that take as parameters molecular features associated with chemical complexity, like the ring complexity or number of stereocenters. Consequently, like Axel and Nils have pointed out before me, the sum of fragment SA scores shouldn’t be the same as that of a whole molecule. This is because you have more chemical motifs in your larger molecule (think of how fingerprints are generated) and because you can’t sum logarithms in the same way you sum real numbers. You can find the details in the original publication: Ertl, P., & Schuffenhauer, A. (2009). Estimation of synthetic accessibility score of drug-like molecules based on molecular complexity and fragment contributions. Journal of Cheminformatics, 1(1), 1–11. https://doi.org/10.1186/1758-2946-1-8 From: Nils Weskamp<mailto:nils.wesk...@gmail.com> Sent: 01 April 2020 12:48 To: Ganesh Shahane<mailto:ganesh7shah...@gmail.com> Cc: rdkit-discuss@lists.sourceforge.net<mailto:rdkit-discuss@lists.sourceforge.net> Subject: Re: [Rdkit-discuss] Synthetic Accessibility (SA) score 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<mailto: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<mailto: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 list Rdkit-discuss@lists.sourceforge.net<mailto:Rdkit-discuss@lists.sourceforge.net> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss _______________________________________________ Rdkit-discuss mailing list Rdkit-discuss@lists.sourceforge.net<mailto:Rdkit-discuss@lists.sourceforge.net> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss _______________________________________________ Rdkit-discuss mailing list Rdkit-discuss@lists.sourceforge.net<mailto:Rdkit-discuss@lists.sourceforge.net> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
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