. 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 1).

Summary of protein structures and associated ligands.^a

System	PDB	RMSD	Ligand/Comment
Androgen receptor

	2AM9^b		TES (O, testosterone)[51]
	2PIX	0.54	DHT (O, dihydrotestosterone, IC₅₀ ∼10 nM) [52]
			FLA (A, flufenamic acid, inhibitor, IC₅₀ ∼ 50 μM)

CDK2

	3MY5^b		CDK2/cyclinA complex with DRB (O): active form[53]
	1PW2^b,c	4.65	Apo CDK2: inactive form[54]
	3PXF	4.59	2AN (A, 2 2AN molecules bound, a and b, K_d ∼37 μM)[55]
	5FP5	4.47	1Y6 (A, 2 1Y6 molecules bound, a and b) [56]
	5FP6	3.95	MFZ (A, 2 MFZ molecules bound, a and b)[56]

Erk5

	4IC8^b		Apo Erk5 (inactive) [57]
	5BYY	3.75	4WG (O, IC₅₀ =∼0.2 μM, undefined protein conformation)[58]
	4ZSG	3.45	4QX, (A, IC₅₀ =∼5 μM, undefined protein conformation)[58]

PTP1B

	2F6F^b		S295F mutant with no ligands (Mg⁺² and Cl⁻)[59]
	1T48	2.75	BB3 (A)[60]
	2NT7	1.50	9O2 (O)[61]
	3CWE	1.07	825 (O, phosphonic acid analog and Mg²⁺)[62]

β2 Adrenergic Receptor (GPCR)

	3SN6^b		P0G (O, Gs protein complex, active form) [63]
	5X7D	2.75	CAU (O, carazolol, inactive form) [64]
			8VS (A, inactive form) [64]

GPR40: Free fatty acid receptor (GPCR)

	4PHU^b		2YB (A, TAK-875, Partial allosteric agonist, site 1)[65]
	5KW2^b		6XQ (A, Lilly: Full allosteric agonist, site 2)[66]
	5TZY	2.04 vs 4PHU	MK6 (A, Partial positive allosteric agonist, site 1, ∼1 nM)[67]
		1.59 vs 5KW2	7OS (A, AgoPAM: Full allosteric agonist, site 2, ∼2 nM)

M2 muscarinic receptor (GPCR)

	3UON ^b		QNB (O, antagonist: inactive form)[68]
	4MQT	2.55	2CU (A, PAM: ∼1 μM, active form)[69]
			IXO (O, active form)[69]

^a)

The first structure listed under each protein was used to initiate the SILCS simulations, unless noted. RMSD in Å between protein structures used for the SILCS simulations and the structures used for identification of ligand binding sites are reported (Table S1 supporting information). Comments includes ligands in the structures with allosteric modulators indicated by (A) and active-site or orthosteric ligands indicated by (O).

^b)

Used for the SILCS simulations and visualization. These structures do not contain the allosteric binding sites. Two different structures were used to initiate the CDK2 and GPR40 SILCS simulations as described in the text.

^c)

Aligned with 3MY5 structure for visualization and analysis.