Table 3.

Examples of structural modifications that are expected to reduce ER binding affinity (based on the analysis of significant descriptors in QSAR models).

ERβ Binder	Structural features		Modified Chemicals	Predicted ERβ binding affinity by MTL models	Experimental ERβ binding affinity
	Descriptor	Suggested modification
logRBAERβ=0.64 ARR=0.79 B01[NO]=0 B09[OC]=1 nArOH=0.2	ARR (negatively correlated with binding affinity)	Increase aromatic ratio by removing alkyl chain	ARR=0.89; % Dscr profile changed=92	−0.44	−0.68
	B01[NO] (negatively correlated with binding affinity)	Add N-O motif	B01[NO]=1; %Dscr profile changed=85	−0.42	N/A
	B09[OC] (positively correlated with binding affinity)	Remove O-C at topological distance 9	B09[OC]=0; %Dscr profile changed=60	−0.15	N/A
	Modifications Not Suggested		nArOH=0.6; %Dscr profile changed=16	1.17	N/A
	nArOH (positively correlated with binding affinity)	Add OH groups attached to aromatic ring

% Dscr profile changed indicates the percentage of descriptors changed in the favorable direction due to the structural modifications. In order to decrease a compound binding affinity, the values should be decreased (increased) for descriptors that positively (negatively) correlate with ER binding affinity. The values of “%Dscr profile changed” were calculated as (number of positively correlated descriptors whose values decreased + number of negatively correlated descriptors whose values increased)/(total number of descriptors).

N/A, not available.