Thank you Dr. Schuffenhauer. This makes sense. -- Best, Ganesh
On Wed, Apr 1, 2020 at 5:36 PM Schuffenhauer, Ansgar < ansgar.schuffenha...@novartis.com> wrote: > Hi Ganesh > > Chemical motives of fragments are not adding simply up. The linkage of two > fragments creates new motives at the fragment linkage points not present in > either of the fragments, and the circular substructures of the once > terminal atoms are disappearing. > Depending on the type of fragmentation and assembly strategy you use, even > stereocenters could be created by fragment linkage > > > Best regards > > > Ansgar Schuffenhauer > Senior Investigator I > T +41 79 608 9063 > ansgar.schuffenha...@novartis.com > > Novartis Pharma AG > NIBR > > -----Original Message----- > From: rdkit-discuss-requ...@lists.sourceforge.net < > rdkit-discuss-requ...@lists.sourceforge.net> > Sent: Mittwoch, 1. April 2020 15:15 > To: rdkit-discuss@lists.sourceforge.net > Subject: Rdkit-discuss Digest, Vol 150, Issue 4 > > Send Rdkit-discuss mailing list submissions to > rdkit-discuss@lists.sourceforge.net > > To subscribe or unsubscribe via the World Wide Web, visit > > https://urldefense.proofpoint.com/v2/url?u=https-3A__lists.sourceforge.net_lists_listinfo_rdkit-2Ddiscuss&d=DwICAg&c=ZbgFmJjg4pdtrnL2HUJUDw&r=5QXEEnQo9VkJH7cIXFb_E4UmFhbbILws-P-WlR4_pzpv_6dQk_-xFQGH00p03i-I&m=w39sgK-SCsl2RmZF3hc9J7GZnaERmOcPmrT2osTwPrc&s=5S3iPLyW1E2knLYrWo9DKJeSOI7RQUIjBnhjpTO2EOs&e= > or, via email, send a message with subject or body 'help' to > rdkit-discuss-requ...@lists.sourceforge.net > > You can reach the person managing the list at > rdkit-discuss-ow...@lists.sourceforge.net > > When replying, please edit your Subject line so it is more specific than > "Re: Contents of Rdkit-discuss digest..." > > > Today's Topics: > > 1. Re: Synthetic Accessibility (SA) score (Alan Kerstjens Medina) > > > ---------------------------------------------------------------------- > > Message: 1 > Date: Wed, 1 Apr 2020 10:58:56 +0000 > From: Alan Kerstjens Medina <alankerstj...@hotmail.com> > To: Ganesh Shahane <ganesh7shah...@gmail.com> > Cc: "rdkit-discuss@lists.sourceforge.net" > <rdkit-discuss@lists.sourceforge.net> > Subject: Re: [Rdkit-discuss] Synthetic Accessibility (SA) score > Message-ID: > < > am0pr09mb3858a943619170c30254a7efa4...@am0pr09mb3858.eurprd09.prod.outlook.com > > > > Content-Type: text/plain; charset="windows-1252" > > 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://urldefense.proofpoint.com/v2/url?u=https-3A__doi.org_10.1186_1758-2D2946-2D1-2D8&d=DwICAg&c=ZbgFmJjg4pdtrnL2HUJUDw&r=5QXEEnQo9VkJH7cIXFb_E4UmFhbbILws-P-WlR4_pzpv_6dQk_-xFQGH00p03i-I&m=w39sgK-SCsl2RmZF3hc9J7GZnaERmOcPmrT2osTwPrc&s=SpDRDob2_4abUGK1H8zKdWcOyMo0Ofrqid7Q_0UuQPs&e= > 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://urldefense.proofpoint.com/v2/url?u=https-3A__github.com_rdkit_rdkit_tree_master_Contrib_SA-5FScore&d=DwICAg&c=ZbgFmJjg4pdtrnL2HUJUDw&r=5QXEEnQo9VkJH7cIXFb_E4UmFhbbILws-P-WlR4_pzpv_6dQk_-xFQGH00p03i-I&m=w39sgK-SCsl2RmZF3hc9J7GZnaERmOcPmrT2osTwPrc&s=-zbY9g94gHDQ0X3ltItFv5aKuAZ12diZZ8MPYS-Dvr8&e= > > 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://urldefense.proofpoint.com/v2/url?u=https-3A__lists.sourceforge.net_lists_listinfo_rdkit-2Ddiscuss&d=DwICAg&c=ZbgFmJjg4pdtrnL2HUJUDw&r=5QXEEnQo9VkJH7cIXFb_E4UmFhbbILws-P-WlR4_pzpv_6dQk_-xFQGH00p03i-I&m=w39sgK-SCsl2RmZF3hc9J7GZnaERmOcPmrT2osTwPrc&s=5S3iPLyW1E2knLYrWo9DKJeSOI7RQUIjBnhjpTO2EOs&e= > _______________________________________________ > Rdkit-discuss mailing list > Rdkit-discuss@lists.sourceforge.net<mailto: > Rdkit-discuss@lists.sourceforge.net> > > https://urldefense.proofpoint.com/v2/url?u=https-3A__lists.sourceforge.net_lists_listinfo_rdkit-2Ddiscuss&d=DwICAg&c=ZbgFmJjg4pdtrnL2HUJUDw&r=5QXEEnQo9VkJH7cIXFb_E4UmFhbbILws-P-WlR4_pzpv_6dQk_-xFQGH00p03i-I&m=w39sgK-SCsl2RmZF3hc9J7GZnaERmOcPmrT2osTwPrc&s=5S3iPLyW1E2knLYrWo9DKJeSOI7RQUIjBnhjpTO2EOs&e= > _______________________________________________ > Rdkit-discuss mailing list > Rdkit-discuss@lists.sourceforge.net<mailto: > Rdkit-discuss@lists.sourceforge.net> > > https://urldefense.proofpoint.com/v2/url?u=https-3A__lists.sourceforge.net_lists_listinfo_rdkit-2Ddiscuss&d=DwICAg&c=ZbgFmJjg4pdtrnL2HUJUDw&r=5QXEEnQo9VkJH7cIXFb_E4UmFhbbILws-P-WlR4_pzpv_6dQk_-xFQGH00p03i-I&m=w39sgK-SCsl2RmZF3hc9J7GZnaERmOcPmrT2osTwPrc&s=5S3iPLyW1E2knLYrWo9DKJeSOI7RQUIjBnhjpTO2EOs&e= > > -------------- next part -------------- > An HTML attachment was scrubbed... > > ------------------------------ > > > > ------------------------------ > > Subject: Digest Footer > > _______________________________________________ > Rdkit-discuss mailing list > Rdkit-discuss@lists.sourceforge.net > > https://urldefense.proofpoint.com/v2/url?u=https-3A__lists.sourceforge.net_lists_listinfo_rdkit-2Ddiscuss&d=DwICAg&c=ZbgFmJjg4pdtrnL2HUJUDw&r=5QXEEnQo9VkJH7cIXFb_E4UmFhbbILws-P-WlR4_pzpv_6dQk_-xFQGH00p03i-I&m=w39sgK-SCsl2RmZF3hc9J7GZnaERmOcPmrT2osTwPrc&s=5S3iPLyW1E2knLYrWo9DKJeSOI7RQUIjBnhjpTO2EOs&e= > > > ------------------------------ > > End of Rdkit-discuss Digest, Vol 150, Issue 4 > ********************************************* > > > _______________________________________________ > Rdkit-discuss mailing list > Rdkit-discuss@lists.sourceforge.net > https://lists.sourceforge.net/lists/listinfo/rdkit-discuss >
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