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| Different inhibitors bound to several allosteric sites on NS5B |
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| Ester participating in Institute for Biophysical Research Retreat, September 2011 |
Allosteric Inhibition of Hepatitis C Viral Polymerase
The primary research focus in the lab is centered on Hepatitis C virus (HCV). HCV affects about 170 million people worldwide and is an important public health concern. I intend to identify novel therapeutic strategies to counter HCV infection by examining, at the molecular level, the physical properties that govern inhibition of the viral RNA-dependent RNA polymerase (NS5B) which replicates the HCV genome. Several classes of allosteric inhibitors bind to the enzyme away from the site of nucleotide addition to a nascent RNA strand. The mechanism of action of these inhibitors is not well understood, and to date there have not been systematic studies to understand the molecular origin of inhibition. I will employ molecular simulation methods to obtain a detailed physical description of the structural and dynamic properties of NS5B in order to determine the source of allosteric inhibition. My goals are to:
i) identify the molecular origin of allosteric inhibition
ii) locate novel allosteric binding sites on the enzyme surface
iii) identify new small molecule inhibitors that can bind to known or newly identified allosteric sites.
Engineering Enzymes for Biofuel Production
Biofuels are being suggested as a fuel alternative since the nonrenewable fossil fuels are becoming more and more limited. We are currently using plants such as soy, palm, and corn for biofuel production. However, researchers are now looking into using algae for biofuels for two main reasons. First, algae are the fastest growing plants and grow at an average of about 40 grams per square meter per day. Second, microalgae are far higher in fuel content than other plants. This project seeks to enhance the production of biofuels from algae by altering algal metabolic pathways via enzyme engineering.