Browsing by Author "Castro Gonzalez, Laura Maria"

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    Computer-aided drug design of activators of the cardiac Kv7.1 potassium channel
    (2023-08) Castro Gonzalez, Laura Maria; Tieleman, Peter; Zaremberg, Vanina; Derksen, Darren Jason; Fraser, Marie Elizabeth
    Long QT syndrome is a heart disease that ends the lives of numerous children and young adults every year. This condition is triggered by the malfunction of some ion channels, including the voltage-gated potassium Kv7.1. In this thesis, multiple computational tools were employed to identify compounds that potentiate the activity of this ion channel. First, a Kv7.1 computational model was created from the Xenopus laevis structure. Then, suitable binding sites in the channel were identified using libraries of known activators of the channel: polyunsaturated fatty acids and endocannabinoids. Selected sites were in silico screened against a large library of small molecules. Multiple criteria such as binding energies, bioavailability and selectivity were employed to finally select compounds for experimental evaluation. This work identified two compounds with high potency and specificity for each binding site studied in the Kv7.1 channel.