Table 2.

ABFE results for the BACE1 Tier 1 compound set. Compound: nomenclature as in³⁰; actives begin with CHEMBL. For each compound, both the more favorable and the less favorable overall binding free energies (BFE, kcal/mol) from the two independent runs are shown. Blocking uncertainties (kcal/mol) and pose-specific ABFE values (kcal/mol) are also presented for the more favorable result. Diff: difference between the two overall BFE values. Docking: docking score computed in this study.

Compound	More favorable BFE run			Less favorable BFE run	Diff	Docking
	Overall BFE	Blocking uncertainty	Pose BFEs	Overall BFE
CHEMBL257091	− 27.1	1.5	− 27.1, − 3.9, − 10.8, − 4.0, − 4.0	− 21	6.1	− 8.8
CHEMBL502121	− 25.1	2	− 13.4, − 8.7, − 25.1, − 14.6, − 6.5	− 19.1	6.0	− 9.4
CHEMBL260834	− 22.8	1.8	− 12.6, − 22.8, − 13.0, − 13.1,4.9	− 17.9	4.9	− 8.7
CHEMBL502289	− 22.6	1.2	− 22.2,0.4, − 9.0, − 1.4, − 22.2	− 22.3	0.3	− 9.2
CHEMBL1092147	− 21.9	1.1	− 19.4, − 21.9, − 1.7,4.9, − 14.9	− 17	4.9	− 8.7
CHEMBL230245	− 21.3	1.9	− 14.9, − 17.8, − 10.2, − 21.3, − 12.8	− 19	2.3	− 9
CHEMBL595065	− 21.1	2.1	− 18.5, − 17.4, − 20.6,6.5, − 20.8	− 18.8	2.3	− 8.5
CHEMBL571433	− 19.8	3	− 4.1, − 19.8, − 10.2, − 1.7, − 7.3	− 10.9	8.9	− 9.6
C01491960	− 18.2	1.7	− 8.3, − 10.3, − 18.1, − 3.4, − 16.9	− 13.7	4.5	− 8.8
CHEMBL404839	− 18.1	1.8	− 8.4, − 18.1, − 12.2, − 13.9, − 15.3	− 18.1	0.0	− 9.3
CHEMBL257645	− 17.1	1.5	− 9.0, − 8.2, − 17.1, − 14.9, − 0.0	− 15.9	1.2	− 8.7
CHEMBL500555	− 17	2.5	− 17.0, − 9.4, − 10.6,3.5, − 9.2	− 17	0.0	− 8.6
C39631886	− 16.5	1.9	− 6.1, − 16.5, − 11.5, − 5.5, − 7.8	− 12.5	4.0	− 8.5
C39559755	− 15.4	1.3	− 5.9,5.2, − 15.4, − 7.5, − 4.0	− 11.7	3.7	− 8.5
CHEMBL1092146	− 15.3	1.9	− 13.2, − 15.3, − 12.6,1.9, − 0.2	− 14.7	0.6	− 8.6
C22874288	− 14.2	1.2	− 14.2, − 3.4,0.9, − 5.8, − 2.1	− 9.6	4.6	− 8.8
CHEMBL595066	− 14	1.3	− 14.0, − 10.2, − 2.1, − 7.8,1.2	− 13.5	0.5	− 8.6
C39674030	− 12.1	2	− 3.9,1.3, − 12.1, − 10.0,0.5	− 11.6	0.5	− 8.8
C28524322	− 11.8	1.7	− 11.8, − 5.7, − 6.7, − 3.9, − 4.6	− 11.6	0.2	− 8.7
CHEMBL517179	− 11.4	1.4	− 11.4, − 4.5, − 3.4, − 7.7, − 0.6	− 9.7	1.7	− 8.9
C39631541	− 10.4	1.8	− 3.9, − 10.4,2.8, − 6.2,4.6	− 9	1.4	− 8.7
C28706109	− 10	1.6	− 5.7,6.4, − 5.8, − 10.0, − 5.2	− 5.8	4.2	− 9
C39674755	− 10	2.4	8.4, − 1.3,1.0,0.3, − 10.0	− 6.4	3.6	− 8.6
C39669490	− 8.9	1.1	− 2.9, − 8.6, − 2.6, − 6.8, − 8.2	− 5	3.9	− 8.6
C35048276	− 8.6	1.4	− 1.1, − 8.6, − 3.7, − 3.1, − 3.9	− 6.7	1.9	− 8.5
C35750025	− 7	2.1	− 7.0,6.3,2.4,1.6,2.9	− 5.6	1.4	− 8.8
CHEMBL1092788	− 6.4	0.9	− 4.9, − 6.0, − 5.8, − 1.8, − 4.8	− 6	0.4	− 8.7
C40318643	− 5	1.3	− 3.5, − 2.0, − 0.8, − 2.8, − 5.0	− 4.7	0.3	− 8.9
C27260756	− 4.8	1.6	0.8, − 4.8, − 0.7, − 1.0, − 1.5	− 2.6	2.2	− 8.9
C36064029	− 4.7	2.4	0.8,2.2, − 2.4,0.2, − 4.7	− 4.1	0.6	− 8.8