Table 1. Summary of BPPS-SIPRIS results for the most significant cluster in each test case.

Protein	PDB	SIPRIS	Focal	BPPS-SIPRIS‡			SIPRIS	Tree	Interpretive comments#
	Structure	mode*	point†	Dist.	Init.	Term.	p-value	level§
Gna1	4ag9A	p=BDF	-	22	57	71	8.5 × 10−7	1	Substrate and homodimeric interfaces
		S	CoA	17	41	87	6.8 × 10−5	0	CoA-binding subdomain
		S	-	23	56	72	9.3 × 10−6	1	DCA-based clustering
		S	-	14	21	107	2.5 × 10−4	1	Structure-based clustering
Rho1	3refB	B	-	20	53	100	8.3 × 10−5	1	(Active site secondary shell)
		C	-	22	55	98	7.8 × 10−7	1	“ “ “ “
Rab4	1z0kA	S	-	10	11	153	2.1 × 10−5	1	(Active site secondary shell)
		C	-	25	91	73	2.6 × 10−6	1	“ “ “ “
		p=B	-	14	23	141	2.9 × 10−8	2	Interface with Rabenosyn-5
		S	-	22	42	122	4.8 × 10−10	2	“ “ “ “
Rab8	3qbtA	p=B	-	13	23	139	5.2 × 10−7	2	Interface with Ocrl1
		p=B	-	12	23	139	6.1 × 10−6	3	Interface with Ocrl1 helix
	4lhwB	p=A	-	10	14	148	8.7 × 10−7	2	Homodimeric interface
EF-Tu	1ob5A	S	-	18	33	150	1.4 × 10−7	1	(GTP to tRNA allosteric link)
		S	-	23	71	112	1.0 × 10−6	2	(GTP/tRNA allosteric link to β-barrel)
		S	1B	22	81	102	1.3 × 10−5	1	Cluster around 5’ base 1 of tRNA
		S	2B	18	47	136	2.6 × 10−6	1	Cluster around 5’ base 2 of tRNA
	1efuA	S	81B	14	49	128	5.2 × 10−5	1	(Nucleotide exchange allosteric network)
	4zv4A	S	291C	21	66	109	0.0060	1	(Mediates hijacking by Tse6 toxin)
CysN	1zunB	S	-	23	79	118	6.3 × 10−5	2	(Allosteric link to β-barrel domain)
eIF4AIII	3ex7H	p=J	-	11	18	128	6.4 × 10−6	1	(ATP to RNA allosteric link)
		S	4J	13	18	128	5.1 × 10−7	1	Cluster around RNA rotation bond
		S	5J	16	41	105	5.5 × 10−4	1	“ “ “ “ “
APE1	5dfiA	H	11P	9	13	238	5.2 × 10-6	0	Abasic site H-bond network
		H	11P	22	99	152	1.6 × 10−6	1	“ “ “ “
		H	-	25	137	114	1.7 × 10−6	1	(Active site secondary shell)
		H	9P	25	137	114	1.9 × 10−7	1	H-bond network positioning abasic site
		H	12P	23	119	132	7.6 × 10−6	1	“ “ “ “ “
Inpp5b	4cmlA	S	-	24	69	216	5.8 × 10−13	0	Active site core residues
		S	-	21	77	208	3.9 × 10−7	1	(Substrate recognition with allosteric link)
		S	-	12	30	255	0.0022	2	(Membrane substrate sequestration)
Inpp5b	3mtcA	S	-	22	91	194	8.0 × 10−7	1	(Substrate recognition with allosteric link)
		S	-	12	29	256	0.0015	2	(Membrane substrate sequestration)
Inpp5e	2xswA	S	-	25	140	148	3.7 × 10−7	1	(Substrate recognition with allosteric link)
		S	-	9	13	275	3.6 × 10−4	2	(Membrane substrate sequestration)
SHIP2	4a9cA	S	-	17	38	260	6.0 × 10−8	1	(Substrate recognition with allosteric link)
		S	-	4	4	294	0.30	2	(Membrane substrate sequestration)
TDG	5hf7A	H	17D	19	97	76	4.1 × 10−4	1	H-bond network around excised base
		H	-	20	98	75	3.5 × 10−5	1	H-bond network around catalytic water
UDG	2dp6A	B	-	13	17	121	1.7 × 10−5	1	H-bond network distinct from TDG

^*Modes: S, spherical expansion; C, core expansion; H, hydrogen bond expansion (involving sidechain interactions); B, hydrogen bond expansion (also involving backbone-to-backbone interactions); P, predefined clustering (residues in the cluster are those interacting with the chain(s) whose pdb identifiers are given to the right of the equal sign).

^†Focal points defining starting residue(s): ‘-‘,analysis was optimized over multiple starting residues (i.e., no focal point); CoA, cluster initiated from the residue closest to Coenzyme A; others, cluster initiated from the residue closest to the indicated position and chain (e.g., 1B = position 1 in pdb chain B).

^‡Nature of the optimum cluster: dist., the number of distinguishing residues within the cluster (total = 25); init., the total number of residues within the cluster; term., the number of residues outside of the cluster.

^§Codes designate pattern residue class: 0, superfamily; 1, family; 2, subfamily; 3, sub-subfamily. In the figures, these correspond to residues with yellow, red, orange and green sidechains, respectively.

^#Comments in parentheses indicate possible functions.