Protein–Ligand

protein–ligand binding and interaction benchmarks

FEP Benchmark Overview

Benchmark	N	Rowan FEP/TMD (2ns, AM1-BCC)					Rowan FEP/TMD (4ns, Mango/RESP)					FEP+ (20ns)				OpenFE (5ns)
Benchmark	N	RMSE	MAE	R²	ρ	min/lig	RMSE	MAE	R²	ρ	min/lig	RMSE	MAE	R²	ρ	RMSE	MAE	R²	ρ
JACS
TYK2	16	0.47	0.37	0.87	0.91	8.9	0.34	0.29	0.93	0.94	13.8	0.47	0.37	0.86	0.92	0.59	0.48	0.80	0.87
BACE	36	1.52	1.14	0.26	0.53	9.3	1.04	0.91	0.56	0.68	13.3	0.75	0.58	0.39	0.55	0.96	0.74	0.30	0.64
CDK2	16	1.10	0.81	0.44	0.69	11.5	1.03	0.84	0.49	0.66	16.2	0.90	0.72	0.42	0.63	0.84	0.70	0.60	0.82
JNK1	21	1.55	1.32	0.19	0.52	20.6	1.54	1.39	0.56	0.76	29.2	0.57	0.46	0.71	0.87	0.85	0.72	0.58	0.77
MCL1	42	1.33	0.97	0.52	0.76	12.2	1.25	0.91	0.64	0.81	14.4	0.86	0.69	0.49	0.67	1.17	0.91	0.49	0.71
p38	34	1.11	0.88	0.47	0.68	15.0	0.97	0.85	0.53	0.69	19.3	0.81	0.63	0.49	0.72	1.25	0.93	0.18	0.44
PTP1B	23	0.92	0.66	0.49	0.63	21.9	0.96	0.71	0.44	0.57	22.8	0.51	0.41	0.85	0.87	0.88	0.71	0.61	0.75
Thrombin	11	0.54	0.42	0.50	0.62	18.8	0.98	0.77	0.53	0.77	18.9	0.53	0.42	0.68	0.78	0.52	0.39	0.57	0.61
Average		1.07	0.82	0.47	0.67	14.8	1.01	0.83	0.58	0.74	18.5	0.68	0.53	0.61	0.75	0.88	0.70	0.52	0.70
Merck
CDK8	32	2.08	1.70	0.73	0.87	50.5	—	—	—	—	—	1.13	0.93	0.56	0.76	1.20	0.99	0.63	0.76
cMet (Neutral)	12	1.39	1.11	0.77	0.75	17.7	—	—	—	—	—	0.83	0.74	0.73	0.83	1.11	0.91	0.73	0.74
cMet (Positive)	12	1.38	1.15	0.66	0.83	28.3	—	—	—	—	—	0.62	0.51	0.78	0.93	1.56	1.25	0.06	0.26
Eg5 (Neutral)	9	1.09	0.97	0.62	0.67	19.0	—	—	—	—	—	0.64	0.55	0.54	0.78	1.01	0.84	0.59	0.65
Eg5 (Positive)	19	1.64	1.47	0.03	0.22	30.2	—	—	—	—	—	0.94	0.68	0.23	0.47	0.93	0.79	0.05	0.23
HIF2a	41	1.89	1.55	0.06	0.22	8.2	—	—	—	—	—	0.77	0.66	0.61	0.66	1.59	1.35	0.40	0.57
PFKFB3	40	1.17	0.93	0.30	0.54	11.8	—	—	—	—	—	0.99	0.77	0.58	0.76	1.11	0.90	0.41	0.63
SHP2	26	2.54	1.90	0.28	0.49	16.8	—	—	—	—	—	1.11	0.92	0.50	0.74	2.06	1.75	0.00	0.13
SYK (Negative)	6	2.37	1.90	0.55	-0.94	60.4	—	—	—	—	—	0.84	0.66	0.60	-0.94	2.40	1.68	0.81	-0.94
SYK (Neutral)	38	1.05	0.88	0.11	0.16	12.4	—	—	—	—	—	0.75	0.58	0.45	0.58	1.03	0.77	0.38	0.43
TNKS2 (Neutral)	21	0.77	0.59	0.41	0.62	8.2	—	—	—	—	—	0.69	0.58	0.63	0.63	0.78	0.60	0.46	0.56
TNKS2 (Positive)	6	0.89	0.80	0.10	0.26	8.9	—	—	—	—	—	0.85	0.70	0.48	0.66	0.53	0.44	0.84	0.83
Average		1.52	1.25	0.38	0.39	22.7	—	—	—	—	—	0.85	0.69	0.56	0.57	1.28	1.02	0.45	0.40
Waterset
BRD4	8	2.24	1.83	0.25	-0.10	6.2	—	—	—	—	—	0.98	0.83	0.00	0.05	0.65	0.59	0.43	0.81
HSP90 (Kung)	11	1.97	1.52	0.51	0.56	7.4	—	—	—	—	—	1.14	0.92	0.69	0.64	3.31	2.55	0.47	0.77
Average		2.11	1.67	0.38	0.23	6.8	—	—	—	—	—	1.06	0.87	0.35	0.34	1.98	1.57	0.45	0.79
Misc
Galectin	26	0.89	0.68	0.57	0.68	13.6	—	—	—	—	—	0.42	0.36	0.76	0.84	0.88	0.72	0.53	0.76
HIV-1 Protease	13	1.36	1.10	0.00	0.13	219.7	—	—	—	—	—	0.76	0.67	0.00	0.05	1.36	1.12	0.02	0.11
Average		1.12	0.89	0.29	0.41	116.6	—	—	—	—	—	0.59	0.51	0.38	0.45	1.12	0.92	0.28	0.43
Overall Average		1.39	1.11	0.40	0.47	26.6	1.01	0.83	0.58	0.74	18.5	0.79	0.64	0.54	0.60	1.19	0.95	0.46	0.54

Benchmark Details

Benchmark

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Method	R²	Spearman's ρ	MAE	RMSE
Rowan FEP/TMD (2ns, AM1-BCC)	0.868	0.909	0.373	0.465
Rowan FEP/TMD (4ns, Mango/RESP)	0.928	0.938	0.291	0.338
FEP+ (20ns)	0.862	0.918	0.371	0.475
OpenFE (5ns)	0.799	0.871	0.476	0.587

This benchmark is from Ross et al. (2023). Rowan FEP/TMD (4ns, Mango/RESP) results are from Rowan Mango 1.0 / RESP (2026-09-30). FEP+ (20ns) results are from Ross et al. (2023). OpenFE (5ns) results are from OpenFE Industry Benchmarks (2024).

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