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Table 1 Binding interactions of the two presented binding modes

From: Modeling of the OX1R–orexin-A complex suggests two alternative binding modes

Ligand residue Interactions with receptor residues  
TM7-mode TM5-mode
Leu16 Alkyl - Val188xl2.36, Glu191xl2.39 -
Tyr17 Aromatic - Phe199xl2.47 Alkyl-π - Met3266.63
Glu18 Salt bridge - Arg3337.28, Lys431.29 Salt bridge - Arg3226.59
H-bond - Tyr411.27 (backbone N)
Leu19 CH–O to backbone - Arg3337.28 -
Leu20 - -
His21 Aromatic - Phe199xl2.47 H-bond - Arg3337.28
Alkyl-π - Val201xl2.49 Cation-π - Arg3286.65
H-bond - Glu1102.68 (backbone carbonyl) Alkyl-π - Met3266.63
H-bond to backbone - Arg3226.59
Gly22 - -
Ala23 Alkyl - Arg3337.28 Alkyl - Arg205xl2.53
H-bond to backbone - Lys3216.58
Gly24 - CH–O hydrogen bond - Asp203 xl2.51
Asn25 H-bond - Cys202xl2.50 (backbone nitrogen) H-bond - Arg3286.65, Lys3216.58 (putative)
H-bond to backbone - Glu204xl2.52, Lys3216.58 (conventional or CH–O)
His26 Aromatic - Tyr3377.32, Phe3407.35 Alkyl-π - Arg3226.59, Val1824.63, Pro2125.35
CH–O hydrogen bond - Asp1072.65 H-bond - Glu204xl2.52
CH–O hydrogen bond - Pro2125.35 (carbonyl)
Ala27 Alkyl - Lys3216.58 Alkyl - Met1834.64
Ala28 Alkyl - Met1834.64 -
H-bond to backbone - Asp203 xl2.51
Gly29 - H-bond to backbone - Asn318 6.55 (requires rotamer change)
Ile30 Alkyl-π - Phe3407.35, His344 7.39 Alkyl - Pro1233.29
Alkyl - Ile3146.51, Ser3237.38 H-bond to backbone - Gln126 3.32
H-bond to backbone - Asn318 6.55
Leu31 Alkyl-π - Tyr215 5.37, His2165.39 Alkyl-π - Trp112xl1.50
Lone pair-π from backbone - Phe219 5.42 Alky - Ile1223.28, Pro1233.29
H-bond to backbone - Ser1032.61
CH–O hydrogen bond to backbone - His344 7.39
Thr32 H-bond - Gln1794.60, Pro1233.29 (backbone carbonyl) Alkyl-π - Phe3407.35, His344 7.39
Alkyl - Ile3146.51
H-bond - Ser3437.38, His344 7.39 (either to threonine hydroxyl or backbone carbonyl)
Leu33 Alkyl-π - His344 7.39, Tyr348 7.43 Alkyl-π - Phe219 5.42
Alkyl - Ile3146.51, Val3477.42 Alkyl - Ile3146.51
H-bond to backbone - Gln126 3.32
NH2 H-bond - Tyr311 6.48 (requires rotamer change) Close to Gln126 3.32 (unfavorable geometry for H-bond)
  1. Interactions divided by type. Unless otherwise noted, the interacting atoms are side-chain atoms. “Requires rotamer change” denotes putative interactions which would take place if a receptor residue adopted a slightly different rotamer. Receptor residues whose mutation has been shown to be detrimental to orexin peptide binding are in bold.