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Friday, October 16, 2015
12:00 AM
1300 Chemistry

Ziah Dean, Cheng Lab
Biophysics Ph.D. Candidate

"Correlating HIV-1 Envelope Glycoprotein Stoichiometry with Viral Infectious Behavior at the Single-Molecule Level"

Over 33 million people live with HIV today. As a model retroviruses, HIV-1 serves as a paradigm for in-depth understanding of host-pathogen interactions. Envelope glycoprotein (Env) trimers on the surface of HIV-1 are essential for interactions with receptors on the host cell, yet the virus appears to possess a low number of Env trimers. The potential heterogeneity in HIV-1 Env content has led to the difficulty in determining the precise number of Env trimers required for optimal infectivity. Following these interactions either endocytic or direct fusion pathways of entry take place, but the molecular events leading to an entry and productive infection remain incompletely understood. This presentation will discuss our progress in quantitatively deciphering HIV-1 viral infectious behavior by studying the fundamental role of HIV-1 viral Env content. In particular, our progress in the development of an unnatural amino acid labeling strategy to specifically label the Env with minimal perturbation to viral functionality will be discussed. Furthermore, we will present progress on an imaging technique to visualize single viruses and subsequently quantitate the number of Env trimers per virion at the single-molecule level. With this system we will be able to determine viral infectivity correlated with Env content. This work would provide a platform for discovery of fundamental knowledge pertaining to the molecular mechanism(s) of HIV-1 transmission and infection.


Sarah Graham, Carlson Lab
Biophysics Ph.D. Candidate

"The Development of Mixed-Solvent Molecular Dynamics for Water-Site Mapping"

Currently, computational methods of water-site mapping are unable to reliably predict the conservation of water molecules in protein binding sites and the functional groups capable of displacing them. The Mixed-Solvent Molecular Dynamics method (MixMD) has been developed to map favorable binding sites on a protein surface through the use of small molecule probes. We have extended and validated this method for hydration site prediction. We applied this protocol to ten proteins and have successfully mapped both conserved and displaced water sites. The results of these calculations can be  used for structure-based drug design efforts to identify water molecules that may be favorably displaced to yield higher affinity ligands.

Ziah Dean & Sarah Graham (U-M Biophysics)