Section: Research

Celia Schiffer, Ph.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Biochemistry and Molecular Pharmacology

Other Affiliation(s):
   Center for AIDS Research
   Interdisciplinary Graduate Program

Structural basis for molecular recognition in HIV Protease

Many biological processes involve complex interdependent molecular recognition events, in which molecules recognize each other with high specificity. Such events include an enzyme acting on its substrate in catalysis, a ligand activating a receptor in regulation and a two dimensional peptide chain assembling into a specific three dimensional fold. The specificity of such molecular recognition events can only be thoroughly understood by detailed analyses of the structures, functions and flexibilities of the molecules.

Investigating molecular recognition of biological macromolecules at the atomic level has been the central objective of my research. In my group we address these questions by using detailed structural and dynamic analyses (both experimental and computational) combined with functional and biophysical assays. This comprehensive approach is essential as molecular recognition is a dynamic event; usually, at least one of the molecular surfaces needs to undergo a conformational change to recognize the other.

Disruption of the life cycle of HIV, the virus that causes AIDS, is the goal of the drugs used to treat infected pediatric patients. The most successful drugs are the protease inhibitors. As the individual virus particles assemble, a series of their necessary components are attached together. For the virus particles to mature and become infectious these necessary components must be cut apart. The protease is the "scissors" molecule which "knows" where to sever these components. Protease inhibitors block these scissors and prevent the virus from maturing. Unfortunately, the virus changes (mutates) and alters the protease so that the inhibitors no longer block the "scissors" action, and the virus is once again infectious (drug resistant). Our strategy is to examine how the protease "knows" where to cut and how this "knowledge" is changed when the protease becomes drug resistant. By understanding how the protease changes, our data will be complementary to the existing efforts of the pharmaceutical industry.

Office: Research 923, Lab 970 L&M
Phone: 508-856-8008
E-mail: Celia.Schiffer@umassmed.edu
Keywords: Biophysics, Drug Design, Structural Biology, Infectious Disease, HIV/AIDS

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