. Author manuscript; available in PMC: 2021 Apr 1.

Published in final edited form as: Biochim Biophys Acta Gen Subj. 2020 Jan 3;1864(4):129519. doi: 10.1016/j.bbagen.2020.129519

Table 3).

Summary of SILCS-Hotspots sites identified in the kinases CDK2 (active and inactive forms) and ERK5, the PTP1B phosphatase, and GPCRs including the β2-adenergic receptor, GPR40 and the M2 muscarinic receptor.^a

Site	Hotspot Rank	Distance	Mean LGFE	# of Fragments	Min. LGFE	Min. LE
CDK2, active

2ANa, A, surface	12	2.7	−3.0	29	−6.3	−0.74
	49	3.5	−2.5	1	−2.5	−0.23
2ANb, A, buried	No adjacent Hotspots
1Y6a, A, upper surface	19	4.9	−2.8	1	−2.8	−0.35
1Y6a, A, upper surface	65	2.7	−2.4	11	−2.7	−0.51
	72	4.2	−2.3	6	−2.7	−0.27
	78	1.1	−2.2	3	−2.6	−0.40
1Y6b, A, buried	5	1.4	−3.2	54	−5.6	−0.76
	92	4.2	−2.1	1	−2.1	−0.30
MFZa, A, surface	8	4.9	−3.1	15	−5.8	−0.73
	12	2.7	−3.0	29	−6.3	−0.74
	49	3.0	−2.5	1	−2.5	−0.23
MFZb, A, buried	5	1.7	−3.2	54	−5.6	−0.76
	92	3.0	−2.1	1	−2.1	−0.30

CDK2, inactive

2ANa, A, surface	22	3.5	−2.7	3	−3.0	−0.43
	33	1.5	−2.6	7	−3.2	−0.61
	70	0.9	−2.2	1	−2.2	−0.28
2ANb, A, buried	6	4.2	−3.1	4	−3.5	−0.37
	22	2.0	−2.7	3	−3.0	−0.43
1Y6, A, upper near V226	50	3.2	−2.5	2	−2.6	−0.47
1Y6, A, upper near V226	51	2.4	−2.5	6	−3.2	−0.41
1Y6, A, lower near G13	34	2.5	−2.6	13	−3.3	−0.56
1Y6, A, lower near G13	70	4.4	−2.2	1	−2.2	−0.28
MFZ, A, surface	6	1.7	−3.1	4	−3.5	−0.37
	22	4.2	−2.7	3	−3.0	−0.43
MFZ, B, buried	34	1.9	−2.6	13	−3.3	−0.56

ERK5

4QX, A	29	0.9	−2.6	18	−3.5	−0.57
	66	3.6	−2.3	2	−2.5	−0.25
	71	3.7	−2.3	2	−2.4	−0.42
4WG, O	8	0.9	−3.1	7	−4.3	−0.72
	25	4.1	−2.7	14	−3.6	−0.45
	71	2.5	−2.3	2	−2.434	−0.42
	78	2.6	−2.2	1	−2.2	−0.36
	86	0.8	−2.1	2	−2.1	−0.35

PTP1B

BB3, A	5	1.0	−3.3	2	−3.8	−0.64
	16	3.0	−2.7	6	−3.1	−0.45
	50	1.6	−2.4	41	−3.6	−0.48
	65	4.5	−2.3	4	−2.5	−0.35
902, O	24	0.6	−2.6	3	−2.7	−0.53
	30	2.3	−2.6	7	−3.2	−0.54
	32	1.9	−2.5	21	−4.7	−0.52
825, O	24	1.3	−2.6	3	−2.7	−0.53
	32	4.8	−2.5	21	−4.7	−0.52

β2 adrenergic receptor (GPCR)

CAU, O	20	1.7	−2.7	1	−2.7	−0.53
	31	1.5	−2.6	22	−3.7	−0.42
	41	1.3	−2.5	2	−2.5	−0.25
	47	3.5	−2.4	6	−2.9	−0.59
	56	2.0	−2.2	1	−2.2	−0.22
	67	3.3	−2.0	1	−2.0	−0.29
8VS, A	23	3.0	−2.7	17	−4.3	−0.47
	58	1.2	−2.2	2	−2.2	−0.41
	60	2.1	−2.2	2	−2.2	−0.23

GPR40 (GPCR)

MK6, A, Site 1^b	27	1.2	−2.9	22	−4.9	−0.58
	57	1.1	−2.3	8	−2.7	−0.45
	61	0.9	−2.1	1	−2.1	−0.36
7OS, A, Site 2^c	12	1.5	−3.1	12	−5.3	−0.65
	29	2.2	−2.7	9	−3.7	−0.57

M2 muscarinic receptor (GPCR)

2CU, A	23	2.3	−3.0	12	−3.9	−0.65
	28	3.2	−2.9	43	−4.7	−0.71
	41	2.0	−2.8	2	−3.3	−0.33
	63	3.4	−2.5	4	−2.8	−0.25
	75	3.2	−2.4	32	−3.2	−0.50
IXO, O	3	2.1	−3.8	2	−3.9	−0.65
	10	0.8	−3.3	32	−6.3	−1.06
	27	3.8	−3.0	57	−5.1	−0.68

^a)

Sites are defined by the allosteric (A) or orthosteric (O) ligands that occupy those sites in the crystallographic structures (Table 1). For certain ligands there are two sites on the protein, with information on both sites including additional identification information such as adjacent protein residue numbers. Distances are in Å and energies in kcal/mol. LE is the ligand efficiency based on the LGFE/# of non-hydrogen atoms.

^b)

SILCS simulation initiated from 5KW2 with ligand in site 2 in the crystal structure.

^c)

SILCS simulation initiated from 4PHU with ligand in site 1 in the crystal structure. In both cases the ligands were removed prior to the SILCS simulations.