Computer-aided drug design of activators of the cardiac Kv7.1 potassium channel

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dc.contributor.advisorTieleman, Peter
dc.contributor.authorCastro Gonzalez, Laura Maria
dc.contributor.committeememberZaremberg, Vanina
dc.contributor.committeememberDerksen, Darren Jason
dc.contributor.committeememberFraser, Marie Elizabeth
dc.date2023-11
dc.date.accessioned2023-08-15T19:26:25Z
dc.date.available2023-08-15T19:26:25Z
dc.date.issued2023-08
dc.description.abstractLong 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.
dc.identifier.citationCastro Gonzalez, L. M. (2023). Computer-aided drug design of activators of the cardiac Kv7.1 potassium channel (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.urihttps://hdl.handle.net/1880/116860
dc.identifier.urihttps://dx.doi.org/10.11575/PRISM/41702
dc.language.isoen
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgary
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectLong QT syndrome
dc.subjectHeart disease
dc.subjectKv7.1 ion channel
dc.subjectComputer-aided drug design
dc.subjectVirtual screening
dc.subjectPolyunsaturated fatty acids
dc.subjectEndocannabinoids
dc.subject.classificationEducation--Sciences
dc.subject.classificationEducation--Health
dc.titleComputer-aided drug design of activators of the cardiac Kv7.1 potassium channel
dc.typemaster thesis
thesis.degree.disciplineBiological Sciences
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.thesis.accesssetbystudentI require a thesis withhold – I need to delay the release of my thesis due to a patent application, and other reasons outlined in the link above. I have/will need to submit a thesis withhold application.
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