Table 1.

Predicted helical protein-protein interactions as targets for synthetic ligands.

PDB code, interface chains; candidate helixa	ΔΔGavg/helix (kcal/mol)b	Helix contributionc	Hot spot residue helix positiond	Chain name/Functione
Examples of Interfaces with Binding Clefts
2i3s, c d; d	2.8	55%	i	c: Cell cycle arrest protein
			i + 1	d: Checkpoint serine/threonine-protein kinase
			i + 3	Function: cell cycle
22ka6, a b; b	2.6	54%	i	a: CREB-binding protein
			i + 1 i + 3	b: Signal transducer and activator of transcription 1-α/β
			i + 4	Function: transcription and gene regulation
2pop, c d; c	2.3	100%	i	c: Mitogen-activated protein kinase kinase kinase 7- interacting protein 1
			i + 1	d: Baculoviral IAP repeat-containing protein
			i + 4	Function: signaling
Examples of Extended Interfaces
2nup, b c; c	2.5	72%	i	b: Protein transport protein Sec24A
			i + 4 i + 5	c: Vesicle-trafficking protein SEC22b
			i + 8	Function: protein transport
2q0o, a c; c	2.4	66%	i	a: Probable transcriptional activator protein traR
			i + 10 i + 13	c: Probable transcriptional repressor tram
			i + 14	Function: transcription and gene regulation
2vgo, a d; d	2.5	24%		a: Serine/threonine-protein kinase 12-A
			i	d: Inner centromere protein A
			i + 8	Function: enzyme (transferase)

^aChains in the complex featuring a helix at the interface; candidate helix to be mimicked is part of the indicated chain.

^bΔΔG_avg/helix is derived from Rosetta computational alanine mutagenesis studies and indicates the average free energy penalty for mutating two or more key residues at the interface to alanine.

^cHelix contribution refers to the proportion of key contact residues positioned on the candidate helix as compared to the chain (see text for a detailed explanation).

^dRelative positioning of the hot spot residues on a helix.

^eDescription of chains featuring the helical interface and cellular function.