(189ao) Conformational Mapping of Viral RNA Elements Using Atomistic Simulations

RNA molecules, similar to proteins, are highly flexible molecules that can undergo conformational changes in response to environmental fluctuations or due to binding of ligands. These conformational changes alter their function and can 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. However, the conformational dynamics of TAR-RNA with and without ligands/inhibitors has not been exhaustively sampled to date. In this work, we will present results from structure-based modeling and enhanced sampling methods to provide a detailed mapping of the conformational landscape of HIV-1 TAR RNA.