Table 4. MMPA-Generated Key Molecular Transformations Shown to Significantly Affect GN-Activity Scores of Synthetically Generated Data^a.

entry	main moiety	+/–	± std	repeats	opposite moiety 1	opposite moiety 2	opposite moiety 3
1	primary amine	addition	0.42 ± 0.25	61	ether [25%]	carbonyl [20%]	secondary amine [10%]
2	lactone	removal	0.41 ± 0.08	35	secondary amine [14%]	tertiary amine [9%]	ether [6%]
3	ester (carboxylate ester)	removal	0.39 ± 0.16	56	secondary amine [9%]	(ether, primary amine) [7%]	tertiary amine [7%]
4	carbonyl	removal	0.37 ± 0.17	96	thiophene [17%]	primary amine [13%]	aryl chloride [9%]
5	nitrile	removal	0.33 ± 0.13	255	aryl chloride [22%]	(thiophene, ether) [12%]	aryl fluoride [5%]
6	thiophene	addition	0.32 ± 0.15	304	(nitrile, secondary amine) [9%]	aniline [8%]	carbonyl [5%]
7	tertiary carboxamide	removal	0.31 ± 0.17	31	thiophene [42%]	aryl chloride [23%]	secondary carboxamide [19%]
8	aryl chloride	addition	0.28 ± 0.16	279	nitrile [20%]	tertiary amine [6%]	aryl fluoride [4%]
9	secondary amine	addition	0.24 ± 0.13	306	tertiary amine [16%]	ether [3%]	nitrile [3%]
10	tertiary amine	removal	0.22 ± 0.09	292	secondary amine [17%]	(aryl chloride, aryl fluoride) [6%]	alkanol [7%]
11	α,β-unsaturated carbonyl	removal	0.21 ± 0.14	33	thiophene [18%]	secondary amine [15%]	aryl chloride [12%]
12	aryl fluoride	addition	0.20 ± 0.13	154	nitrile [16%]	tertiary amine [12%]	alkanol [3%]

^aListed are the molecular replacements that correlate with a strong increase of the predicted GN activity, most likely due to improved permeability according to our initial curation, by either addition or removal of each specific main moiety (+/−). The top three exchange counterparts in the matched molecular pairs are shown as opposite moieties. denotes the average change of the GN-activity score (limits from 0 to 1), linked to the respective transformations with associated standard deviation. “Repeats” indicates the number of transformations that contain the “main moiety”.