Classification of Protein-Protein Interfaces for Recognition of Similar Spatial and Chemical Organizations

Contact: Shira Mintz mintzshi@post.tau.ac.il

Pilot dataset: 64 Interfaces extracted from common protein complexes.
Ranking: I2I-SiteEngine was applied to all pairs of dataset interfaces (except for where surface area differs by more than 50%). Each time a certain interface is used as a query. It was compared to all other dataset interfaces ranking them in a decreasing order according to their similarity to this query.
Clustering: A clustering algorithm uses the rank lists of all pairwise comparisons to cluster the interfaces to different groups. In this preliminary implementation we applied a greedy clustering procedure that performs several iterations with decreasing cut off values defined by the match score.

Obtained Clusters: Below we present preliminary results of the classification of our pilot dataset of interfaces. Using I2I-SiteEngine, 64 interfaces were clustered to 22 different groups. Due to the relatively low number of interfaces under comparison, some clusters are single membered. In the table below we provide the list of the full classification.  For each Interface the table specifies the PDB code of the complex, followed by the chains that constitute the interfaces as well as the SCOP classification of these chains (family/fold).

Num	Cluster members	Complex Description	Family / Fold (defined by SCOP)
			First Chain	Second Chain
1	1ao7AE	Hla-A 0201 in complex with Human T-Cell Receptor Beta	MHC antigen-recognition domain/ MHC antigen-recognition domain	V set domains (antibody variable domain-like) / Immunoglobulin-like beta-sandwich)
2	1okuBF 1okvBE 1h27BE	Cyclin A with Inhibitor Cyclin A with Inhibitor Cyclin A with Peptide From P27	Cyclin / Cyclin-like Cyclin / Cyclin-like Cyclin / Cyclin-like	peptide, no SCOP entry peptide, no SCOP entry peptide, no SCOP entry
3	1eakAP 1rlqCR	Catalytic Domain Of Prommp-2 E404Q Mutant with inhibitor C-Src (Sh3 Domain) with Rlp2	Fibronectin type II module / Kringle-like SH3-domain / SH3-like barrel	peptide, no SCOP entry peptide, no SCOP entry
4	1g6rBH 1fo0BH	Beta T Cell Receptor with Major Histocompatibility Complex Class I Molecule Beta T Cell Receptor with Major Histocompatibility Complex Class I Molecule	V set domains / antibody variable domain-like V set domains / antibody variable domain-like	MHC antigen-recognition domain / MHC antigen-recognition domain MHC antigen-recognition domain / MHC antigen-recognition domain
5	1czvAB 1cdtAB 1dfnAB 1d2hAB 1c1yAB 1kbaAB 1ef7AB 1axcAC 1b77AB 1kklAH	Coagulation Factor V Cytotoxin Defensin Glycine N-Methyltransferase Ras-Related Protein Rap-1a complexed with Proto-Onkogene Serinethreonine Protein Kappa-Bungarotoxin Cathepsin X Proliferating Cell Nuclear Antigen Sliding Clamp Hprk Protein in complex with Phosphocarrier Protein Hpr	Discoidin domain / Galactose-binding domain-like Snake venom toxins / Snake toxin-like Defensin / Defensin-like Glycine N-methyltransferase / S-adenosyl-L-methionine-dependent methyltransferases G proteins / P-loop containing nucleoside triphosphate hydrolases Snake venom toxins / Snake toxin-like Papain-like / Cysteine proteinases DNA polymerase processivity factor/ DNA clamp DNA polymerase processivity factor/ DNA clamp HPr kinase HprK C-terminal domain/ PEP carboxykinase-like	Discoidin domain / Galactose-binding domain-like Snake venom toxins / Snake toxin-like Defensin / Defensin-like Glycine N-methyltransferase / S-adenosyl-L-methionine-dependent methyltransferases Ras-binding domain, RBD / beta-Grasp (ubiquitin-like) Snake venom toxins / Snake toxin-like Papain-like / Cysteine proteinases DNA polymerase processivity factor/ DNA clamp DNA polymerase processivity factor/ DNA clamp HPr-like / HPr-like
6	1h26BE 1h28BE 1jsuBC	Cyclin A2 in complex with Cellular Tumor Antigen P53 Cyclin A2 in complex with Recruitment Peptide From P107 Cyclin A in complex with P27 (Kip1)	Cyclin / Cyclin-like Cyclin / Cyclin-like Cyclin / Cyclin-like	peptide, no SCOP entry peptide, no SCOP entry P27(KIP1) fragment 22-106 / P27(KIP1) fragment 22-106
7	1ijdAC 1lghGJ	Light-Harvesting Complex Light Harvesting Complex	Light-harvesting complex subunits / Light-harvesting complex subunits Light-harvesting complex subunits / Light-harvesting complex subunits	Light-harvesting complex subunits / Light-harvesting complex subunits Light-harvesting complex subunits / Light-harvesting complex subunits
8	1cseEI 1tgsZI 1acbEI 1bzxEI 1gl1AI 3tecEI 1sbnEI	Subtilisin Carlsberg in Complex With Eglin-C Trypsinogen in Complex With Trypsin Inhibitor Alpha-Chymotrypsin in Complex With Eglin C Trypsin In Complex With Bovine Pancreatic Trypsin Inhibitor Alpha-Chymotrypsin in complex with Protease Inhibitor Lcmi II Thermitase Complex With Eglin-C Subtilisin in Complex With Eglin C Mutant With Leu 45 Replaced By Arg	Subtilases / Subtilisin-like Eukaryotic proteases / Trypsin-like serine proteases Eukaryotic proteases / Trypsin-like serine proteases Eukaryotic proteases / Trypsin-like serine proteases Eukaryotic proteases / Trypsin-like serine proteases Subtilases / Subtilisin-like Subtilases / Subtilisin-like	CI-2 family of serine protease inhibitors / CI-2 family of serine protease inhibitors Animal Kazal-type inhibitors / Ovomucoid/PCI-1 like inhibitors CI-2 family of serine protease inhibitors / CI-2 family of serine protease inhibitors Small Kunitz-type ihibitors & BPTI-like toxins / BPTI-like PMP inhibitors / PMP inhibitors CI-2 family of serine protease inhibitors / CI-2 family of serine protease inhibitors CI-2 family of serine protease inhibitors / CI-2 family of serine protease inhibitors
9	1ao7AD	Hla-A 0201 in complex with Human T-Cell Receptor Alpha	MHC antigen-recognition domain / MHC antigen-recognition domain	V set domains (antibody variable domain-like) / Imnoglobulin-like beta-sandwich
10	1a6aBC 1f3jBP 1d9kDP 1aqdBC 1jk8BC 1dlhBC	Clip Bound To Class II Mhc Hla-Dr3 Mhc Class II Nod bound to Lysozyme C Mhc I-Ak B Chain bound to Conalbumin Peptide Hla-Dr1 Class II Histocompatibility Protein bound to Hla-A2 Antigenic Peptide Mhc Class II Hla-Dq8 bound to Insulin B Peptide Hla-Dr1 Class II Histocompatibility Protein bound to Antigenic Peptide	MHC antigen-recognition domain / MHC antigen-recognition domain MHC antigen-recognition domain / MHC antigen-recognition domain MHC antigen-recognition domain / MHC antigen-recognition domain MHC antigen-recognition domain / MHC antigen-recognition domain MHC antigen-recognition domain / MHC antigen-recognition domain MHC antigen-recognition domain / MHC antigen-recognition domain	peptide, no SCOP entry peptide, no SCOP entry peptide, no SCOP entry peptide, no SCOP entry peptide, no SCOP entry peptide, no SCOP entry
11	1d09AB	Aspartate Transcarbamoylase Complexed With N-Phosphonacetyl- L-Aspartate	Aspartate/ornithine carbamoyltransferase /ATC-like	Aspartate carbamoyltransferase, Regulatory-chain, C-terminal domain / Rubredoxin-like
12	1gagAB	Insulin Receptor Kinase In Complex With A Bisubstrate Inhibitor	Protein kinases, catalytic subunit / Protein kinase-like (PK-like)	peptide, no SCOP entry
13	1cxzAB 1hcoAB	Rhoa Complexed With Protein Kinase Pknprk1 Hemoglobin	G proteins / P-loop containing nucleoside triphosphate hydrolases Globins / Globin-like	Effector domain of the protein kinase pkn/prk1 / Long alpha-hairpin Globins / Globin-like
14	1ydtEI	Camp-Dependent Protein Kinase, In Complex With H89 Protein Kinase Inhibitor	Protein kinases, catalytic subunit / Protein kinase-like (PK-like)	peptide, no SCOP entry
15	1hfoAB 1otgAB	Migration Inhibitory Factor 5-Carboxymethyl-2-Hydroxymuconate Isomerase	MIF-related / Tautomerase/MIF 5-carboxymethyl-2-hydroxymuconate isomerase (CHMI) / Tautomerase/MIF	MIF-related / Tautomerase/MIF 5-carboxymethyl-2-hydroxymuconate isomerase (CHMI) / Tautomerase/MIF
16	1bt6AB 1irjAB 1dt7AB 1e8aAB	P11 (S100a10), Ligand Of Annexin Migration Inhibitory Factor-Related Protein S100 Calcium-Binding Protein S100a12	Calcyclin (S100) / EF Hand-like S100 proteins / EF Hand-like S100 proteins / EF Hand-like S100 proteins / EF Hand-like	Calcyclin (S100) / EF Hand-like S100 proteins / EF Hand-like S100 proteins / EF Hand-like S100 proteins / EF Hand-like
17	1b48AB 10gsAB 1pd212 1axdAB	Glutathione S-Transferase Glutathione S-Transferase P1-1 Hematopoietic Prostagladin D Synthase Glutathione S-Transferase I	2 interacting domains for chain A: Glutathione S-transferase (GST), N-terminal domain / Thioredoxin fold and Glutathione S-transferase (GST), C-terminal domain / Glutathione S-transferase (GST), C-terminal domain 2 interacting domains for chain A: Glutathione S-transferase (GST), N-terminal domain / Thioredoxin fold and Glutathione S-transferase (GST), C-terminal domain / Glutathione S-transferase (GST), C-terminal domain 2 interacting domains for chain 1: Glutathione S-transferase (GST), N-terminal domain / Thioredoxin fold and Glutathione S-transferase (GST), C-terminal domain / Glutathione S-transferase (GST), C-terminal domain 2 interacting domains for chain A: Glutathione S-transferase (GST), N-terminal domain / Thioredoxin fold and Glutathione S-transferase (GST), C-terminal domain / Glutathione S-transferase (GST), C-terminal domain	2 interacting domains for chain B: Glutathione S-transferase (GST), N-terminal domain / Thioredoxin fold and Glutathione S-transferase (GST), C-terminal domain / Glutathione S-transferase (GST), C-terminal domain 2 interacting domains for chain B: Glutathione S-transferase (GST), N-terminal domain / Thioredoxin fold and Glutathione S-transferase (GST), C-terminal domain / Glutathione S-transferase (GST), C-terminal domain 2 interacting domains for chain 2: Glutathione S-transferase (GST), N-terminal domain / Thioredoxin fold and Glutathione S-transferase (GST), C-terminal domain / Glutathione S-transferase (GST), C-terminal domain 2 interacting domains for chain B: Glutathione S-transferase (GST), N-terminal domain / Thioredoxin fold and Glutathione S-transferase (GST), C-terminal domain / Glutathione S-transferase (GST), C-terminal domain
18	1iruOP 1iruFG 1g0uOP 1pmaAC	20s Proteasome 20s Proteasome Proteasome Proteasome	Proteasome subunits / Ntn hydrolase-like Proteasome subunits / Ntn hydrolase-like Proteasome subunits / Ntn hydrolase-like Proteasome subunits / Ntn hydrolase-like	Proteasome subunits / Ntn hydrolase-like Proteasome subunits / Ntn hydrolase-like Proteasome subunits / Ntn hydrolase-like Proteasome subunits / Ntn hydrolase-like
19	1ic2CD 1gl2AB 1gl2BC 1gk4AB 1if3AB	Tropomyosin Endosomal Snare Core Complex Endosomal Snare Core Complex Vimentin Envelope Polyprotein Gp160	Tropomyosin / Parallel coiled-coil SNARE fusion complex / Parallel coiled-coil SNARE fusion complex / Parallel coiled-coil Vimentin coil / Parallel coiled-coil peptide, no SCOP entry	Tropomyosin / Parallel coiled-coil SNARE fusion complex / Parallel coiled-coil SNARE fusion complex / Parallel coiled-coil Vimentin coil / Parallel coiled-coil peptide, no SCOP entry
20	1ceeAB	Gtp-Binding Rho-Like Protein in complex with Wasp protein.	G proteins / P-loop containing nucleoside triphosphate hydrolases	peptide, no SCOP entry
21	1eboAB	Virus Membrane-Fusion Subunit Gp2	Virus ectodomain / Stalk segment of viral fusion proteins	Virus ectodomain / Stalk segment of viral fusion proteins
22	1fzaAB	Fibrinogen	Fibrinogen coiled-coil and central regions / Parallel coiled-coil	2 interacting domains for chain B: Fibrinogen C-terminal domain-like / Fibrinogen C-terminal domain-like and Fibrinogen coiled-coil and central regions / Parallel coiled-coil