Bioinformatics and receptor mechanisms of psychotropic drugs.
One important aspect in biotechnology is gene discovery and target validation for drug discovery. Information from the human genome (HUGO) project may be used to deduce the amino acid sequence of all proteins produced in the human body. However, knowing the amino acid sequence of a protein is not the same as knowing its function. Identification of novel molecular targets for discovery of new, safer and more efficient therapeutic drugs from the human genome sequences requires multidisciplinary research efforts, including proteomics, structural biology and bioinformatics. In addition to possible effects on gene expression, most of the currently used therapeutic drugs either have enzymes or membrane proteins as their molecular targets of action. These membrane proteins include transporters of small molecules across cell membranes, ion channels, or receptors that convey signals from one side of a membrane to the other. Our research group as well as others have used computational techniques, along with biotechnology, molecular biology and other experimental techniques, to construct detailed 3-dimensional models of transporter proteins and G-protein coupled receptors (GPCRs), which are the molecular targets of action of psychotropic drugs. The models have been used to simulate the molecular dynamics and study the ligand binding and signal transduction mechanisms of these receptors. The use of bioinformatics, as exemplified in our modelling of GPCRs, is only one of the key factors for success in post-genomic research for new targets for therapeutic drugs.
Dahl
S G
SG
Department of Pharmacology, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, 9037 Tromsø, Norway. sgd@fagmed.uit.no
Edvardsen
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Kristiansen
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Sylte
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D000818:Animals; D001709:Biotechnology; D002352:Carrier Proteins / Q000187:drug effects; D002417:Cattle; D019295:Computational Biology; D015195:Drug Design; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects; D011955:Receptors, Drug / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012243:Rhodopsin / Q000737:chemistry
D002352:Carrier Proteins; D011619:Psychotropic Drugs; D011956:Receptors, Cell Surface; D011955:Receptors, Drug; D011985:Receptors, Serotonin; D012243:Rhodopsin; D019204:GTP-Binding Proteins