Cofactors

The PDBe RelLig pipeline automatically identifies cofactor-like ligands in the PDB by comparing their 2D structural similarity to cofactor classes found in the CoFactor database. The CoFactor database contains 27 manually curated classes of organic enzyme cofactors and information about the associated enzymes, including their EC numbers. For each cofactor class, a representative small molecule was selected from the PDB based on its close structural match to the template molecule using PARITY similarity. A minimum similarity threshold was also defined, and the list of enzyme EC numbers was expanded using data from BRENDA.

Annotation process

The pipeline analyzes input PDB ligands by calculating their similarity to template molecules in each cofactor class. If the similarity meets the minimum threshold for any cofactor class, the ligand is further compared to the representative molecule of that class. If the similarity remains above the threshold and the ligand interacts with a protein that has an EC number matching the cofactor class, the ligand is classified as cofactor-like.

Data

Details of templates, representatives, thresholds and ec numbers used for the cofactor classes can be found in the folder pdberellig/data/cofactors.

Class id	Template	Representative	Threshold
1	TDPTHW	TPP	0.6
2	FAD	FAD	0.87
3	FMN	FMN	0.86
4	NAD2	NAD	0.68
5	PNS	PNS	1.0
6	COAM	COA	0.67
7	PLP	PLP	0.78
8	0HG	GSH	0.42
9	BTN	BTN	0.58
10	FFO	FFO	0.94
11	B12	B12	0.84
12	ASC	ASC	1.0
13	MQ7	MQ7	1.0
14	UQ2	UQ1	0.53
15	MSS	MGD	0.43
16	H4B	H4B	0.78
17	MDO	MDO	1.0
18	SAM3	SAM	0.6
19	F43	F43	0.94
20	COM	COM	1.0
21	TP7	TP7	1.0
22	HEA	HEA	0.52
24	DPM	DPM	0.97
25	PQQ	PQQ	1.0
26	1TY	TPQ	0.55
27	TRQ	TRQ	0.88
28	LPA	LPA	1.0

Examples

PDBe RelLig pipeline identifies the PDB Ligand 8FL as a cofactor-like molecule similar to TPP (Thiamine Diphosphate) and writes the outputs with ligand interacting proteins from the PDB with corresponding EC numbers.

{
    "8FL": {
        "template": {
            "id": "TDPTHW",
            "similarity": 0.722
        },
        "representative": {
            "id": "TPP",
            "similarity": 0.963
        },
        "pdb_chains": [
            {
                "pdb_id": "5xvt",
                "auth_asym_id": "A",
                "struct_asym_id": "A",
                "uniprot_id": "P34736",
                "ec_number": "2.2.1.1"
            },
            {
                "pdb_id": "5xuf",
                "auth_asym_id": "A",
                "struct_asym_id": "A",
                "uniprot_id": "P34736",
                "ec_number": "2.2.1.1"
            },
            {
                "pdb_id": "8vzb",
                "auth_asym_id": "D",
                "struct_asym_id": "D",
                "uniprot_id": "A0A3C0TX30",
                "ec_number": "4.1.1.8"
            },
            {
                "pdb_id": "8vzb",
                "auth_asym_id": "A",
                "struct_asym_id": "A",
                "uniprot_id": "A0A3C0TX30",
                "ec_number": "4.1.1.8"
            },
            {
                "pdb_id": "8vza",
                "auth_asym_id": "C",
                "struct_asym_id": "C",
                "uniprot_id": "A0A3C0TX30",
                "ec_number": "4.1.1.8"
            },
            {
                "pdb_id": "8vza",
                "auth_asym_id": "B",
                "struct_asym_id": "B",
                "uniprot_id": "A0A3C0TX30",
                "ec_number": "4.1.1.8"
            },
            {
                "pdb_id": "8vzb",
                "auth_asym_id": "B",
                "struct_asym_id": "B",
                "uniprot_id": "A0A3C0TX30",
                "ec_number": "4.1.1.8"
            }
        ]
    }
}