Our research interests are to determine the three dimensional structures of proteins and molecular assemblies such as viruses and to identify the structural underpinnings and requirements for the self-assembly, stability and targeting specificities of viral capsids. We further use this information as a knowledge base to design novel protein shells that polyvalently display multiple copies of peptides/proteins of interest. We employ X-ray crystallography, cryo-EM, computational, bioinformatics and genetic methods to investigate these areas of research.

Viruses are highly evolved macromolecular assemblages that perform a variety of functions during their life cycle: self-assemble to form uniform capsids, selective packaging of the genome, binding and followed by delivery of the genetic material to the susceptible target cells. Simple viruses such as non-enveloped viruses form capsids that are homogeneous in their composition and quaternary architecture. Hence are amenable for structural and functional analyses. 

In collaboration with Professor Glen Nemerow's group at TSRI, we recently determined the crystal structure of Human adenovirus at 3.5Å resolution (Reddy et al, 2010), the biggest virus structure yet determined to date. Highlights of the structure include novel conformation of the Penton base structure, where the fiber shaft is seen inserted deep into the PB-pore. One of the cement proteins, VIII has been conclusively identified located on the capsid interior at two different locations. Identification of other cement proteins are underway.

We are also actively involved in maintaining and developing the popular virus structure database, VIPERdb (http://viperdb.scripps.edu) of spherical virus structures and their computational and bio-informatics analysis (Carrillo-Tripp et al, 2009).