. Author manuscript; available in PMC: 2014 Jul 15.

Published in final edited form as: Bioorg Med Chem. 2012 Dec 4;21(14):4051–4057. doi: 10.1016/j.bmc.2012.11.023

Table 1.

Classification of helical protein interfaces.

Types of PPIs	PDB code, helix sequence	Arrangement of hot spot residues on the target helix	ΔΔG (kcal/mol)¹	ΔSASA²	Known Inhibitors	Protein names Function
Interfaces with Binding Clefts
	1YCR ¹⁹FSDLWKLLPE²⁸	i	3.8	131.1	Small molecules^{70, 77} Helix mimetics^{59, 60, 80, 101–105}	MDM2 (gray): coactivator p53 (green): transcriptional activator. Function:Apoptotic signaling, cell-cycle arrest
		i + 4	4.4	136.7
		i+ 7	2.0	73.4
		(Avg)	(3.4)	(113.7)
	1Y3A ⁵WYDFLM¹⁰	i	4.2	168.3	Linear peptide¹⁰⁶ Cyclic peptides¹⁰⁷	Giα 1 (gray): Guanine nucleotide-binding protein alpha-1 subunit KB752 (green): peptide Function: Signaling protein
		i + 3	3.3	93.9
		i +4	1.8	83.8
		(Avg)	(3.1)	(115.3)
	1BXL ⁵⁷⁸LAIIGDDI⁵⁸⁵	i	2.7	102.2	Small molecules^{82, 108–110} Helix mimetics^{50, 111–113}	BCL-XL (gray): BAK peptide (green): Function: apoptosis
		i + 3	2.2	87.3
		i +7	1.2	79.3
		(Avg)	(2.0)	(89.6)
	1JSU ⁸⁵PEFYYR⁹⁰	i	2.9	122.1	Small molecules^{114, 115}	CDK2(gray): cyclin dependent kinase-2 P27(KIP1): kinase inhibitor (blue, helix in green) Function: Enzyme Kinase
		i+1	4.9	116.8
		i+3	1.1	64.6
		(Avg)	(3.0)	(101.2)
Extended Helical Interfaces
	1AIK ⁶²⁸WMEWDREINNYTSLI⁶⁴²	i	2.8	160.69	Small molecules^{116, 117} Linear peptide⁹¹ and helix mimetics^{53, 55, 91–94}	HR1 (gray): N-terminal heptad repeat of HIV-1 GP41 HR2 (green): C-terminal heptad repeat of HIV-1 GP-41 Function: glycoprotein
		i + 3	1.92	124.62
		i+ 10	2.01	77.32
		i+ 14	1.76	92.59
		(Avg)	(2.12)	(113.8)
	3BXK ¹⁹⁶1IYAAMMIMEYYRQS1⁹⁷⁴	i	1.9	130.49	No known inhibitors	Ca2+-CaM (gray): calmodulin Cav 2.1 IQ (green): voltage gated calcium channels-Isoleucine-glutamine Function: Signaling protein
		i + 1	1.6	105.38
		i + 4	1.0	104.8
		i + 6	3.1	111.97
		i+ 10	2.7	103.28
		i+11	2.0	107.88
		(Avg)	(2.05)	(110.6)
	1NVW ⁹³⁰FGIYLTNILKTEEGN⁹⁴⁴	i	1.64	43.73	Small molecule^{99, 100} Helix mimetics⁵²	Ras (gray): guanine nucleotide binding protein Sos (blue, helix in green): Ras-specific guanine nucleotide exchange factor Function: signaling protein
		i+6	1.11	57.75
		i+13	1.10	57.98
		i + 15	2.35	67.70
		(Avg)	(1.55)	(56.79)
w	1K90 ⁸²EEEIREAFRVFDK⁹⁴	i	0.71	78.71	No known inhibitors	EF(gray): Edema factor Calmodulin (blue, helix in green): Function: Anthrax Toxin
		i+3	1.99	90.67
		i+6	1.84	105.7
		i+7	1.26	81.14
		i+10	1.53	64.99
		(Avg)	(1.47)	(84.24)

Calculated using computational alanine scanning suite of Rosetta.⁶⁵

Obtained from PocketQuery.^{33, 66} Numbers in parentheses refer to average of ΔΔG or ΔSASA values for hot spot residues.