Studying the Structure-Function Relationship of the Platelet-Activating Factor Receptor Using Molecular Dynamics Simulations

Nicholas Walker and Blake Mertz
Department of Biology and C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26505

Presentation Category: Biological Sciences (Poster Presentation)

Student’s Major: Biology

The platelet-activating factor receptor (PAFR) is a G protein-coupled receptor that plays a critical role in inflammatory responses associated with asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and pathogenic invasions. Drug development targeting PAFR has been a decades-long pursuit that has yet to produce any major successes. Recently an X-ray crystal structure of PAFR was solved, making it possible to carry out structure-function studies to facilitate identification of natural or synthetic antagonists of PAFR that could be used to decrease inflammatory responses and address the long-term effects of chronic inflammation. Through the use of molecular dynamics (MD) simulations, we can acquire a deep understanding of the structure-function relationship of PAFR. We carried out MD simulations of PAFR embedded in a lipid bilayer, starting from two conformations of the protein: one bound to an antagonist and one bound to an inverse agonist. Our results show how specific regions of PAFR dynamically change to adjust the binding pocket to form respective ligand-receptor complexes.

Funding:

Program/mechanism supporting research/creative efforts: a West Virginia SURE program