(231i) Long Time-Scale Atomistic Simulations of HIV-1 TAR RNA

RNA molecules are highly flexible molecules that can undergo conformational changes in response to environmental fluctuations or due to ligand binding. These conformational changes play an important role in many cellular functions and can either activate or terminate processes that are vital to lifecycles of cellular machinery. Viral RNA molecules are a good example of conformationally adapting molecules that have evolved to switch between many functions such as translation and replication. Specifically, the replication of human immunodeficiency virus Type-1 (HIV-1) results from a conformational change in the RNA transactivation response element (TAR RNA) elicited by the binding of the Tat protein. Since the discovery of TAR RNA, it has been explored as a potential target for inhibitors designed to block HIV-1 replication and many experimental structures have been resolved. However, the conformational dynamics of TAR-RNA with and without ligands/inhibitors has not been exhaustively sampled to date. In this talk I will present results from long classical MD simulations of 13 uniquely resolved experimental TAR structures performed to provide a detailed mapping of the conformational space of HIV-1 TAR RNA that has relevance to ligand recognition.