Noskov, Sergei Yu.Vogel, Hans J.Fanning, John Keenan2018-06-262018-06-262018-06-12Fanning, J. K. (2018). Novel Electrostatic Mechanisms Controlling the Conformational Switching of L-plastin (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/32009http://hdl.handle.net/1880/106783L-plastin is an actin-bundling protein that promotes the motility of both hematopoietic and metastatic cancer cells. The high definition structure of the calcium-binding regulatory domain of human L-plastin was recently determined, allowing computational research on this portion of the protein. The Drude polarizable force field was used to provide accurate computational simulations of the calcium-binding domain in conjunction with experimental validation to shown that L-plastin can regulate calcium-binding, and thus actin-bundling, through internal electrostatic interactions. Through this work the Drude force field was also benchmarked, to show that it provides comparable results to classical force fields with the added ability to simulate polarizability. Overall, a novel mechanism which allows L-plastin to self-regulate its calcium-binding affinity was developed.engUniversity 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.L-plastinProtein conformational dynamicsMD SimulationCalcium-binding regulationPolarizable force fieldEducation--SciencesBiologyBiophysicsBiochemistrymaster thesis10.11575/PRISM/32009