{"206241":{"#nid":"206241","#data":{"type":"event","title":"Kazi Shefaet Rahman - Ph.D. Proposal Presentation","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003ECo-Advisors\u003C\/strong\u003E\u003Cbr \/\u003EStephen C. Harvey, Ph.D. (Georgia Tech)\u003Cbr \/\u003ENael A. McCarty, Ph.D. (Emory University)\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECommittee\u003C\/strong\u003E\u003Cbr \/\u003ECheng Zhu, Ph.D. (Georgia Tech)\u003Cbr \/\u003EPeter J. Ludovice, Ph.D. (Georgia Tech)\u003Cbr \/\u003EKing Jordan, Ph.D. (Georgia Tech)\u003Cbr \/\u003E\u003Cbr \/\u003EThe CFTR chloride channel mediates salt and water movement across epithelia. Mutations in the gene encoding CFTR and the resulting dysfunction in the protein cause cystic fibrosis, the most common life-shortening disease among Caucasians. The long-term goal of our research is to identify the conformational changes in the CFTR channel pore that underlie the transitions between conducting and non-conducting states, and to identify the conduction pathway of the open state. CFTR is a member of the ABC transporter superfamily, \u0026nbsp;but it is the only member known to exhibit ion channel activity. Transporters generally function by means of an \u0022alternating access\u0022 cycle in which the substrate binding site is alternately exposed to the inside or the outside of the cell through conformational changes in the protein, \u0026nbsp;without there ever being\u0026nbsp;a\u0026nbsp;continuous path from one side to the other. In CFTR, however, a continuous pore allowing anion conduction\u0026nbsp;must\u0026nbsp;exist, and conformational changes are thought to gate the pore open and closed. The structural basis for this fundamental difference is unknown. Using homology modeling and molecular dynamics simulations, we have identified possible structures for the open and closed states of CFTR and conformational transition pathways between them. We have also used our simulations to predict novel side chain interactions that are involved in stabilizing particular channel states, which have been confirmed experimentally.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EIn this proposal, we will refine our homology modeling and molecular dynamics simulations through the use of a template that bears even closer resemblance to the purported CFTR structure. We will test the hypothesis that channel activity evolved in CFTR by converting the conformational changes associated with alternating access transport \u2014 as found in other ABC transporters \u2014 into the formation of a stable open state. We will identify sites where interactions between residues either hinder channel opening or promote the stabilization of the open states. In addition, we will use molecular dynamics simulations to study ion conduction in the open channel pore.\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003E\u201cMolecular Modeling and Simulations of The Conformational Changes Underlying Channel Activity in CFTR\u201d\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Molecular Modeling and Simulations of The Conformational Changes Underlying Channel Activity in CFTR"}],"uid":"27547","created_gmt":"2013-04-12 14:04:49","changed_gmt":"2016-10-08 02:03:16","author":"Chris Ruffin","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2013-04-26T17:30:00-04:00","event_time_end":"2013-04-26T19:30:00-04:00","event_time_end_last":"2013-04-26T19:30:00-04:00","gmt_time_start":"2013-04-26 21:30:00","gmt_time_end":"2013-04-26 23:30:00","gmt_time_end_last":"2013-04-26 23:30:00","rrule":null,"timezone":"America\/New_York"},"extras":[],"groups":[{"id":"65448","name":"Bioengineering Graduate Program"}],"categories":[],"keywords":[{"id":"569","name":"bioengineering"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1788","name":"Other\/Miscellaneous"}],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022mailto:chris.ruffin@ibb.gatech.edu\u0022\u003EMr. Christopher Ruffin\u003C\/a\u003E\u003C\/p\u003E","format":"limited_html"}],"email":[],"slides":[],"orientation":[],"userdata":""}}}