Identifying specificity-altering
allosteric mutations in the PDZ domain using novel computational tools
PIA WAHI-SINGH
BASIS AHWATUKEE HIGH SCHOOL – 11TH GRADE
&
DR. BANU OZKAN LAB, DEPARTMENT OF BIOPHYSICS ARIZONA STATE UNIVERSITY
BASIS AHWATUKEE HIGH SCHOOL – 11TH GRADE
&
DR. BANU OZKAN LAB, DEPARTMENT OF BIOPHYSICS ARIZONA STATE UNIVERSITY
Introductory Video:
Abstract:
My goal is to decode and modulate protein interaction networks involved in disease pathways by targeting the most ubiquitous interaction domain protein, the PDZ Domain (PDZ). PDZs are the universal outlets of many protein residue networks that wire diverse functions in our cells. This links them to our most puzzling diseases such as Alzheimer’s, Parkinson’s, cancer, depression, etc. What makes PDZs exceptionally unique is that PDZs evolve to have different dynamics properties tailored to mediate different functions. Not only can they be exploited to wire new protein networks through engineered biology, they can be the perfect tool to modulate disease-related proteins. Therefore, PDZs can be “the most influential drug” target. Yet what is hindering the outbreak of this novel drug target is the missing technology that can incorporate their conformational dynamics. I plan to address this by employing a complete set of novel tools that use computational methods developed in the Ozkan lab and are able to correctly simulate PDZ conformational dynamics. Using these tools, I will identify residues that are at distal positions from the binding site, yet allosterically control binding site conformational dynamics. I will then utilize evolutionary information to predict possible mutations to alter PDZs’ binding specificity.
Technical Presentation:
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If you have a question, please fill out the question form, so I can contact you directly with my answer.
I will also post these questions, with my response, in the comments section so they can be viewed publicly.