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One of the challenges of modern pharmacology is specificity. Despite therapeutic effects, drugs can often have side effects. The biological basis for this has to do with the proteins and receptors that the drug targets and binds to. Many target receptors are connected to more than one biochemical pathway or more commonly, the drug is not specific enough to exclusively bind one particular receptor.
One solution is to develop artificial target receptors that are only activated by ligands not found anywhere in the cell. The idea is that when "installed" in a cell, these artificial receptor-ligand pairs will only activate one biochemical pathway—sometimes a completely new one—without interfering with the cell's other functions.
Field - Cell - Receptors - Cell - Membrane
The field has mainly focused on cell receptors, and especially those located on the cell membrane. These receptors have enormous biomedical and pharmacological potential, as they translate extracellular signals into specific intracellular functions. But because they often bind to multiple intracellular proteins with interactions that are not currently very well understood, it has proven difficult to design synthetic receptors with novel signaling functions.
Now, scientists in Patrick Barth's lab at EPFL, the Ludwig Institute for Cancer Research Lausanne and Baylor College of Medicine in the US have developed a powerful computational method to accurately model and engineer synthetic orthogonal receptor-ligand pairs that bind together and transmit biochemical signals in the cell with high selectivity.
Method - Aspects - Biology - Membrane - Protein
The method integrates various aspects of synthetic computational biology (e.g. membrane protein homology modeling, ligand and protein docking)...
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