VenusX Benchmark Leaderboard

Residue-level Binary Classification

Cross-family

Performance on Cross-family splits (Out-of-distribution). Higher is better.

Act: Active Sites | BindI: Binding Sites | Evo: Conserved Sites | Motif: Functional Motif | Dom: Functional Domain

Model	Type	AUPR	Precision	Recall	F1-Positive	Macro-F1
SaProt (AF_650M)	Seq-Structure	0.185	0.241	0.072	0.110	0.538
Ankh (Base)	Sequence-only	0.166	0.190	0.025	0.045	0.507
ProtSSN (k20_h512)	Seq-Structure	0.156	0.241	0.014	0.026	0.498
ESM2 (t30)	Sequence-only	0.143	0.278	0.060	0.098	0.533
ProtBert	Sequence-only	0.131	0.131	0.020	0.035	0.501
ESM2 (t33)	Sequence-only	0.143	0.126	0.031	0.050	0.507
SaProt (AF_35M)	Seq-Structure	0.114	0.132	0.036	0.056	0.510
GVP-GNN	Structure-only	0.101	0.019	0.001	0.002	0.485

Model	Type	AUPR	Precision	Recall	F1-Positive	Macro-F1
SaProt (AF_35M)	Seq-Structure	0.230	0.634	0.135	0.223	0.599
SaProt (AF_650M)	Seq-Structure	0.182	0.661	0.135	0.224	0.600
ProtSSN (k20_h512)	Seq-Structure	0.095	0.379	0.029	0.053	0.514
ProtBert	Sequence-only	0.112	0.416	0.048	0.086	0.530
Ankh (Base)	Sequence-only	0.145	0.437	0.086	0.144	0.559
ESM2 (t30)	Sequence-only	0.133	0.525	0.078	0.136	0.556
ESM2 (t33)	Sequence-only	0.159	0.581	0.108	0.181	0.579
GVP-GNN	Structure-only	0.040	0.000	0.000	0.000	0.488

Model	Type	AUPR	Precision	Recall	F1-Positive	Macro-F1
Ankh (Base)	Sequence-only	0.275	0.387	0.169	0.235	0.595
SaProt (AF_650M)	Seq-Structure	0.274	0.456	0.111	0.178	0.568
SaProt (AF_35M)	Seq-Structure	0.272	0.382	0.172	0.238	0.596
ProtBert	Sequence-only	0.243	0.482	0.009	0.017	0.489
ESM2 (t33)	Sequence-only	0.262	0.403	0.122	0.187	0.572
ESM2 (t30)	Sequence-only	0.235	0.374	0.097	0.154	0.555
ProtSSN (k20_h512)	Seq-Structure	0.227	0.452	0.034	0.062	0.511
GVP-GNN	Structure-only	0.101	0.176	0.035	0.058	0.506

Model	Type	AUPR	Precision	Recall	F1-Positive	Macro-F1
ProtBert	Sequence-only	0.348	0.472	0.231	0.310	0.628
ESM2 (t33)	Sequence-only	0.456	0.566	0.384	0.457	0.704
SaProt (AF_650M)	Seq-Structure	0.441	0.504	0.350	0.414	0.680
ESM2 (t30)	Sequence-only	0.433	0.510	0.432	0.467	0.707
SaProt (AF_35M)	Seq-Structure	0.408	0.485	0.411	0.445	0.695
Ankh (Base)	Sequence-only	0.394	0.499	0.303	0.377	0.662
ProtSSN (k20_h512)	Seq-Structure	0.390	0.390	0.365	0.412	0.678
GVP-GNN	Structure-only	0.329	0.329	0.453	0.399	0.661

Model	Type	AUPR	Precision	Recall	F1-Positive	Macro-F1
SaProt (AF_650M)	Seq-Structure	0.564	0.572	0.444	0.500	0.632
SaProt (AF_35M)	Seq-Structure	0.525	0.548	0.349	0.427	0.594
ProtBert	Sequence-only	0.508	0.588	0.138	0.223	0.501
ESM2 (t33)	Sequence-only	0.506	0.530	0.367	0.433	0.593
ESM2 (t30)	Sequence-only	0.470	0.496	0.360	0.417	0.578
GVP-GNN	Structure-only	0.468	0.519	0.087	0.149	0.462
Ankh (Base)	Sequence-only	0.449	0.494	0.280	0.357	0.552
ProtSSN (k20_h512)	Seq-Structure	-	-	-	-	-

Mixed-family

Performance on Mixed-family splits (In-distribution). Higher is better.

Model	Type	AUPR	Precision	Recall	F1-Positive	Macro-F1
Ankh (Base)	Sequence-only	0.873	0.862	0.700	0.773	0.883
ESM2 (t30)	Sequence-only	0.855	0.826	0.676	0.744	0.868
ESM2 (t33)	Sequence-only	0.852	0.845	0.682	0.755	0.874
ProtBert	Sequence-only	0.764	0.791	0.565	0.659	0.825
SaProt (AF_650M)	Seq-Structure	0.745	0.812	0.511	0.627	0.808
SaProt (AF_35M)	Seq-Structure	0.688	0.818	0.408	0.544	0.767
GVP-GNN	Structure-only	0.523	0.735	0.362	0.485	0.736
ProtSSN (k20_h512)	Seq-Structure	0.465	0.523	0.209	0.329	0.658

Model	Type	AUPR	Precision	Recall	F1-Positive	Macro-F1
ESM2 (t30)	Sequence-only	0.912	0.859	0.859	0.859	0.926
Ankh (Base)	Sequence-only	0.907	0.849	0.866	0.857	0.925
ESM2 (t33)	Sequence-only	0.904	0.869	0.830	0.849	0.921
ProtBert	Sequence-only	0.857	0.855	0.694	0.766	0.878
SaProt (AF_650M)	Seq-Structure	0.838	0.827	0.768	0.796	0.893
SaProt (AF_35M)	Seq-Structure	0.807	0.813	0.705	0.755	0.871
ProtSSN (k20_h512)	Seq-Structure	0.801	0.818	0.705	0.757	0.873
GVP-GNN	Structure-only	0.611	0.730	0.519	0.607	0.795

Model	Type	AUPR	Precision	Recall	F1-Positive	Macro-F1
ESM2 (t33)	Sequence-only	0.899	0.856	0.806	0.831	0.910
Ankh (Base)	Sequence-only	0.895	0.882	0.735	0.802	0.896
ESM2 (t30)	Sequence-only	0.862	0.816	0.783	0.799	0.894
ProtBert	Sequence-only	0.771	0.805	0.610	0.694	0.839
SaProt (AF_650M)	Seq-Structure	0.734	0.809	0.554	0.658	0.820
SaProt (AF_35M)	Seq-Structure	0.724	0.819	0.520	0.636	0.809
ProtSSN (k20_h512)	Seq-Structure	0.715	0.790	0.507	0.618	0.800
GVP-GNN	Structure-only	0.342	0.810	0.091	0.164	0.569

Model	Type	AUPR	Precision	Recall	F1-Positive	Macro-F1
Ankh (Base)	Sequence-only	0.884	0.846	0.789	0.817	0.895
ESM2 (t33)	Sequence-only	0.874	0.851	0.748	0.796	0.884
ESM2 (t30)	Sequence-only	0.855	0.824	0.775	0.799	0.885
SaProt (AF_650M)	Seq-Structure	0.802	0.841	0.615	0.710	0.837
ProtBert	Sequence-only	0.779	0.784	0.678	0.727	0.845
SaProt (AF_35M)	Seq-Structure	0.767	0.821	0.582	0.681	0.821
ProtSSN (k20_h512)	Seq-Structure	0.716	0.772	0.550	0.642	0.799
GVP-GNN	Structure-only	0.661	0.748	0.525	0.618	0.786

Model	Type	AUPR	Precision	Recall	F1-Positive	Macro-F1
Ankh (Base)	Sequence-only	0.673	0.674	0.467	0.552	0.700
ESM2 (t33)	Sequence-only	0.666	0.661	0.467	0.547	0.696
SaProt (AF_650M)	Seq-Structure	0.642	0.635	0.472	0.542	0.689
ESM2 (t30)	Sequence-only	0.634	0.648	0.433	0.519	0.679
ProtBert	Sequence-only	0.591	0.636	0.353	0.454	0.644
SaProt (AF_35M)	Seq-Structure	0.574	0.632	0.322	0.427	0.629
GVP-GNN	Structure-only	0.560	0.591	0.344	0.435	0.636
ProtSSN (k20_h512)	Seq-Structure	-	-	-	-	-

Model	Type	AUPR	Precision	Recall	F1-Positive	Macro-F1
ESM2 (t33)	Sequence-only	0.446	0.605	0.329	0.427	0.707
Ankh (Base)	Sequence-only	0.421	0.634	0.260	0.369	0.678
ESM2 (t30)	Sequence-only	0.408	0.598	0.289	0.390	0.689
ProtBert	Sequence-only	0.340	0.547	0.238	0.332	0.659

Model	Type	AUPR	Precision	Recall	F1-Positive	Macro-F1
ESM2 (t30)	Sequence-only	0.186	1.000	0.001	0.002	0.480
ESM2 (t33)	Sequence-only	0.174	0.000	0.000	0.000	0.479
ProtBert	Sequence-only	0.169	1.000	0.001	0.002	0.480
Ankh (Base)	Sequence-only	0.167	0.000	0.000	0.000	0.479

Fragment-level Multi-class Classification

MF50

Performance on InterPro datasets (MF50 split). Higher is better.

Model	Type	Accuracy	Precision	Recall	Macro-F1	MCC
SaProt (AF_650M)	Seq-Structure	0.928	0.830	0.830	0.825	0.926
GVP-GNN	Structure-only	0.907	0.826	0.833	0.822	0.906
SaProt (AF_35M)	Seq-Structure	0.928	0.810	0.823	0.807	0.926
ProtSSN (k20_h512)	Seq-Structure	0.891	0.773	0.774	0.764	0.889
Ankh (Base)	Sequence-only	0.824	0.661	0.665	0.647	0.821
ESM2 (t30)	Sequence-only	0.819	0.659	0.670	0.647	0.815
ESM2 (t33)	Sequence-only	0.814	0.603	0.634	0.605	0.810
ProtBert	Sequence-only	0.736	0.618	0.636	0.609	0.731

Model	Type	Accuracy	Precision	Recall	Macro-F1	MCC
SaProt (AF_650M)	Seq-Structure	0.986	0.968	0.956	0.957	0.984
SaProt (AF_35M)	Seq-Structure	0.976	0.943	0.929	0.931	0.971
GVP-GNN	Structure-only	0.972	0.901	0.882	0.884	0.967
ProtSSN (k20_h512)	Seq-Structure	0.972	0.940	0.948	0.931	0.967
ESM2 (t30)	Sequence-only	0.937	0.834	0.819	0.809	0.926
ESM2 (t33)	Sequence-only	0.934	0.755	0.775	0.753	0.922
ProtBert	Sequence-only	0.927	0.838	0.794	0.790	0.914
Ankh (Base)	Sequence-only	0.920	0.733	0.732	0.718	0.906

Model	Type	Accuracy	Precision	Recall	Macro-F1	MCC
SaProt (AF_650M)	Seq-Structure	0.950	0.868	0.875	0.863	0.950
SaProt (AF_35M)	Seq-Structure	0.939	0.857	0.858	0.849	0.938
ProtSSN (k20_h512)	Seq-Structure	0.915	0.804	0.807	0.793	0.915
GVP-GNN	Structure-only	0.914	0.763	0.768	0.757	0.913
Ankh (Base)	Sequence-only	0.866	0.727	0.729	0.716	0.865
ESM2 (t30)	Sequence-only	0.853	0.681	0.684	0.667	0.852
ESM2 (t33)	Sequence-only	0.841	0.682	0.682	0.669	0.840
ProtBert	Sequence-only	0.828	0.644	0.646	0.627	0.827

Model	Type	Accuracy	Precision	Recall	Macro-F1	MCC
ProtSSN (k20_h512)	Seq-Structure	0.914	0.564	0.556	0.556	0.907
SaProt (AF_650M)	Seq-Structure	0.927	0.546	0.562	0.552	0.921
ESM2 (t33)	Sequence-only	0.906	0.547	0.543	0.542	0.898
SaProt (AF_35M)	Seq-Structure	0.901	0.509	0.505	0.504	0.892
Ankh (Base)	Sequence-only	0.901	0.508	0.501	0.499	0.892
ESM2 (t30)	Sequence-only	0.884	0.458	0.461	0.457	0.875
ProtBert	Sequence-only	0.884	0.455	0.458	0.452	0.875
GVP-GNN	Structure-only	0.807	0.387	0.371	0.370	0.791

Pairwise Functional Similarity Scoring

F50

Performance on fragment-level splits (F50). Metric is AUC (%). Higher is better.

Model	Type	AUC (%)
ESM-IF	Seq-Structure	96.5
Foldseek (3Di-AA)	Alignment	96.1
Foldseek (3Di)	Alignment	96.0
SaProt (AF2_35M)	Seq-Structure	95.8
TM-align	Alignment	94.6
TM-VEC	Seq-Structure	93.6
ProtT5 (xl-uniref50)	Seq-Enc-Dec	91.8
ProstT5	Seq-Structure	90.8
SaProt (PDB_650M)	Seq-Structure	82.8
ProtSSN (k20_h512)	Seq-Structure	79.1
ProtBert	Sequence-only	71.4
Ankh (base)	Seq-Enc-Dec	69.6
ESM2 (t30)	Sequence-only	69.4
ESM-1B	Sequence-only	67.6
MIF-ST	Seq-Structure	65.9
ESM2 (t36)	Sequence-only	65.8
BLAST	Alignment	52.9
ESM2 (t33)	Sequence-only	50.2

Model	Type	AUC (%)
ProstT5	Seq-Structure	99.5
TM-VEC	Seq-Structure	98.6
ProtT5 (xl-uniref50)	Seq-Enc-Dec	98.5
SaProt (PDB_650M)	Seq-Structure	98.1
ESM-IF	Seq-Structure	95.0
SaProt (AF2_35M)	Seq-Structure	94.3
Foldseek (3Di)	Alignment	92.6
Foldseek (3Di-AA)	Alignment	92.6
TM-align	Alignment	90.1
Ankh (base)	Seq-Enc-Dec	88.9
ProtSSN (k20_h512)	Seq-Structure	88.4
MIF-ST	Seq-Structure	86.1
ProtBert	Sequence-only	84.9
ESM-1B	Sequence-only	84.5
ESM2 (t30)	Sequence-only	77.6
ESM2 (t33)	Sequence-only	73.0
ESM2 (t36)	Sequence-only	71.3
BLAST	Alignment	52.4

Model	Type	AUC (%)
Foldseek (3Di-AA)	Alignment	88.4
Foldseek (3Di)	Alignment	88.3
ProtT5 (xl-uniref50)	Seq-Enc-Dec	71.0
TM-align	Alignment	67.7
TM-VEC	Seq-Structure	67.4
ESM2 (t36)	Sequence-only	63.9
Ankh (base)	Seq-Enc-Dec	63.9
SaProt (PDB_650M)	Seq-Structure	62.6
SaProt (AF2_35M)	Seq-Structure	61.9
ESM-IF	Seq-Structure	61.3
MIF-ST	Seq-Structure	61.3
ProtSSN (k20_h512)	Seq-Structure	60.9
ESM-1B	Sequence-only	57.0
ProstT5	Seq-Structure	55.6
ProtBert	Sequence-only	54.6
BLAST	Alignment	54.0
ESM2 (t30)	Sequence-only	52.4
ESM2 (t33)	Sequence-only	49.3

Model	Type	AUC (%)
TM-VEC	Seq-Structure	99.4
SaProt (PDB_650M)	Seq-Structure	98.9
ProstT5	Seq-Structure	98.5
ProtT5 (xl-uniref50)	Seq-Enc-Dec	98.2
ESM2 (t33)	Sequence-only	92.1
ESM2 (t36)	Sequence-only	90.1
ESM-1B	Sequence-only	87.2
Ankh (base)	Seq-Enc-Dec	86.7
SaProt (AF2_35M)	Seq-Structure	85.3
ProtBert	Sequence-only	85.1
ESM2 (t30)	Sequence-only	84.3
ESM-IF	Seq-Structure	80.4
TM-align	Alignment	76.6
Foldseek (3Di)	Alignment	74.8
Foldseek (3Di-AA)	Alignment	74.7
ProtSSN (k20_h512)	Seq-Structure	72.4
MIF-ST	Seq-Structure	50.2
BLAST	Alignment	49.9

Model	Type	AUC (%)
ProtT5 (xl-uniref50)	Seq-Enc-Dec	98.5
ProstT5	Seq-Structure	98.5
TM-VEC	Seq-Structure	98.2
Ankh (base)	Seq-Enc-Dec	97.6
ESM-IF	Seq-Structure	97.1
SaProt (AF2_35M)	Seq-Structure	96.0
SaProt (PDB_650M)	Seq-Structure	91.7
ESM-1B	Sequence-only	89.2
ProtBert	Sequence-only	85.3
ProtSSN (k20_h512)	Seq-Structure	82.9
MIF-ST	Seq-Structure	78.6
ESM2 (t30)	Sequence-only	78.0
ESM2 (t36)	Sequence-only	66.5
ESM2 (t33)	Sequence-only	62.2

P50

Performance on protein-level splits (P50). Metric is AUC (%). Higher is better.

Model	Type	AUC (%)
Foldseek (3Di)	Alignment	96.5
Foldseek (3Di-AA)	Alignment	96.5
Ankh (base)	Seq-Enc-Dec	90.4
TM-VEC	Seq-Structure	89.9
ProstT5	Seq-Structure	80.7
ProtT5 (xl-uniref50)	Seq-Enc-Dec	78.1
SaProt (AF2_35M)	Seq-Structure	74.6
ESM-1B	Sequence-only	73.8
ESM2 (t36)	Sequence-only	72.9
BLAST	Alignment	71.7
ESM-IF	Seq-Structure	70.2
ESM2 (t33)	Sequence-only	70.0
ESM2 (t30)	Sequence-only	69.2
ProtBert	Sequence-only	68.7
SaProt (PDB_650M)	Seq-Structure	68.2
MIF-ST	Seq-Structure	65.9
ProtSSN (k20_h512)	Seq-Structure	64.8

Model	Type	AUC (%)
Ankh (base)	Seq-Enc-Dec	91.8
TM-VEC	Seq-Structure	82.4
Foldseek (3Di)	Alignment	80.6
Foldseek (3Di-AA)	Alignment	80.1
ProstT5	Seq-Structure	79.2
ProtT5 (xl-uniref50)	Seq-Enc-Dec	77.1
SaProt (AF2_35M)	Seq-Structure	71.9
SaProt (PDB_650M)	Seq-Structure	71.1
ESM-1B	Sequence-only	69.8
ESM2 (t36)	Sequence-only	67.6
ProtBert	Sequence-only	66.8
ESM-IF	Seq-Structure	65.6
ESM2 (t30)	Sequence-only	65.5
ESM2 (t33)	Sequence-only	62.3
ProtSSN (k20_h512)	Seq-Structure	61.2
MIF-ST	Seq-Structure	59.2
BLAST	Alignment	51.1

Model	Type	AUC (%)
Foldseek (3Di)	Alignment	99.0
Foldseek (3Di-AA)	Alignment	99.0
Ankh (base)	Seq-Enc-Dec	98.9
ProstT5	Seq-Structure	98.2
TM-VEC	Seq-Structure	96.2
ProtT5 (xl-uniref50)	Seq-Enc-Dec	95.6
SaProt (PDB_650M)	Seq-Structure	93.8
SaProt (AF2_35M)	Seq-Structure	92.7
ESM2 (t36)	Sequence-only	92.1
ESM-IF	Seq-Structure	90.6
ESM2 (t33)	Sequence-only	89.0
ESM-1B	Sequence-only	88.4
ESM2 (t30)	Sequence-only	87.5
ProtSSN (k20_h512)	Seq-Structure	86.2
ProtBert	Sequence-only	84.2
MIF-ST	Seq-Structure	80.3

Model	Type	AUC (%)
TM-VEC	Seq-Structure	71.7
ESM2 (t36)	Sequence-only	70.0
ProstT5	Seq-Structure	69.8
Ankh (base)	Seq-Enc-Dec	69.7
SaProt (PDB_650M)	Seq-Structure	68.3
ProtBert	Sequence-only	68.2
ESM2 (t30)	Sequence-only	68.2
ProtT5 (xl-uniref50)	Seq-Enc-Dec	67.6
SaProt (AF2_35M)	Seq-Structure	66.6
MIF-ST	Seq-Structure	66.3
ESM2 (t33)	Sequence-only	66.1
ESM-IF	Seq-Structure	66.0
Foldseek (3Di)	Alignment	64.9
Foldseek (3Di-AA)	Alignment	64.7
ProtSSN (k20_h512)	Seq-Structure	64.0
ESM-1B	Sequence-only	58.4
BLAST	Alignment	56.2

Model	Type	AUC (%)
Ankh (base)	Seq-Enc-Dec	88.5
ProtT5 (xl-uniref50)	Seq-Enc-Dec	85.1
ProstT5	Seq-Structure	79.3
SaProt (AF2_35M)	Seq-Structure	78.8
ProtBert	Sequence-only	77.9
ESM2 (t30)	Sequence-only	77.4
SaProt (PDB_650M)	Seq-Structure	76.1
ESM-1B	Sequence-only	74.7
ESM-IF	Seq-Structure	70.5
ProtSSN (k20_h512)	Seq-Structure	69.4
ESM2 (t36)	Sequence-only	66.7
MIF-ST	Seq-Structure	66.7
ESM2 (t33)	Sequence-only	66.4
TM-VEC	Seq-Structure	59.9

VenusX: Unlocking Fine-Grained Functional Understanding of Proteins