Study of human orexin-1 and -2 G-protein-coupled receptors with novel and published antagonists by modeling, molecular dynamics simulations, and site-directed mutagenesis

Biochemistry

Volumn 51, Issue 15, 2012, Pages 3178-3197

  Heifetz, Alexander ^a   Morris, G Benjamin ^c   Biggin, Philip C ^c   Barker, Oliver ^a   Fryatt, Tara ^a   Bentley, Jonathan ^a   Hallett, David ^a   Manikowski, Dominique ^b   Pal, Sandeep ^a   Reifegerste, Rita ^b   Slack, Mark ^b   Law, Richard ^a  

^a EVOTEC UK LTD   (United Kingdom)

^b EVOTEC AG   (Germany)

^c UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID SEQUENCE; BINDING AFFINITIES; CLASS A; CONFORMATIONAL DIFFERENCES; DOMAIN EXCHANGE; ENERGY METABOLISM; FLEXIBLE DOCKING; G PROTEIN COUPLED RECEPTORS; HOMOLOGY MODELING; INTERHELICAL INTERACTIONS; KEY FEATURE; MD SIMULATION; MOLECULAR DYNAMICS SIMULATIONS; PHYSIOLOGICAL FUNCTIONS; RECEPTOR MODEL; SITE DIRECTED MUTAGENESIS; SLEEP-WAKE CYCLES; STATIC MODEL; TRANSMEMBRANE HELICES;

AMINO ACIDS; BINDING ENERGY; COMPUTER SIMULATION; MOLECULAR DYNAMICS;

SPACE DIVISION MULTIPLE ACCESS;

1 (2 METHYL 6 BENZOXAZOLYL) 3 (1,5 NAPHTHYRIDIN 4 YL)UREA; 1 [5 (2 FLUOROPHENYL) 2 METHYLTHIAZOL 4 YL] 1 [2 (5 PHENYL 1,3,4 OXADIAZOL 2 YLMETHYL)PYRROLIDIN 1 YL]METHANONE; ADENOSINE A2A RECEPTOR; ALMOREXANT; BETA 2 ADRENERGIC RECEPTOR; COMPLEMENTARY DNA; DOPAMINE 3 RECEPTOR; EP 009 9513; EP 109 0092; G PROTEIN COUPLED RECEPTOR; JNJ 10397049; N ETHYL 2 [(6 METHOXYPYRIDIN 3 YL)(TOLUENE 2 SULFONYL)AMINO] N PYRIDIN 3 YLMETHYL ACETAMIDE; OREXIN 1 RECEPTOR; OREXIN 1 RECEPTOR ANTAGONIST; OREXIN 2 RECEPTOR; OREXIN 2 RECEPTOR ANTAGONIST; RECEPTOR BLOCKING AGENT; RHODOPSIN; SB 649868; SB 674042; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; ANIMAL CELL; ARTICLE; BINDING AFFINITY; BRAIN; CALCIUM TRANSPORT; CHIMERA; CRYSTAL STRUCTURE; DRUG BINDING SITE; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG TARGETING; ENERGY METABOLISM; FEEDING; HUMAN; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MOLECULAR MODEL; NEUROENDOCRINE SYSTEM; NONHUMAN; POINT MUTATION; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; SITE DIRECTED MUTAGENESIS; SLEEP WAKING CYCLE;

AMINO ACID SEQUENCE; BINDING SITES; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MODELS, MOLECULAR; MOLECULAR DYNAMICS SIMULATION; MOLECULAR SEQUENCE DATA; MUTAGENESIS, SITE-DIRECTED; NEUROPEPTIDES; PROTEIN CONFORMATION; RECEPTORS, G-PROTEIN-COUPLED;

EID: 84859906798     PISSN: 00062960     EISSN: 15204995     Source Type: Journal    
DOI: 10.1021/bi300136h     Document Type: Article

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