Undergraduate Research Journal

Molecular Analysis of the Interaction Between Staphylococcus aureus
Protein Sbi and Immune System Protein C3d
Wilson Rodriguez, Ronald D. Gorham Jr., Chris A. Kieslich,
Aliana López de Victoria, Dimitrios Morikis
Department of Bioengineering
University of California, Riverside
Abstract
Protein-protein interactions form the basis of cellular communication, signaling, and regulation.
These interactions are governed by non-covalent forces, originating from electrostatic and
van der Waals interactions at atomic resolution. Electrostatic interactions are often crucial to
protein recognition and binding, particularly for highly and oppositely charged proteins. We
examined the interactions between secreted protein Sbi from antibiotic-resistant strains of
S. aureus with host immune system protein C3d, using electrostatic clustering and free energy
analysis. We used the computational framework called Analysis of Electrostatic Similarities Of
Proteins (AESOP) to perform computational alanine scans and we generated a series of protein
variants with perturbed electrostatic properties. To elucidate the effect of each mutation in
association (defined as recognition plus binding) of Sbi with C3d, we performed electrostatic
clustering and association free energy calculations. The analysis of our data revealed which
charged amino acids are important for the formation of the C3d-Sbi complex, thus pointing out
gain-of-association or loss-of-association mutations. This knowledge will form the basis for
the design of proteins with tailored binding properties, and thus tailored biological function,
by incorporating multiple critical mutations. This project will guide the development of novel
therapeutics for treatment of infections by S. aureus.
Mentors
Faculty Mentor: Dimitrios Morikis (left)
Graduate Student Mentor: Ronald D. Gorham Jr. (right)
Department of Bioengineering
Wilson has conducted research in my lab for a little over a year. He
is working on molecular level interactions between the bacterium
S. aureus and the human immune system, using theoretical
physicochemical methods. Specifically, he studies how the S. aureus protein Sbi disrupts the role
of the human protein C3d as a link between innate and adaptive immunity. The role of C3d is to
augment antibody response, and Sbi, and other bacterial proteins, disrupt this beneficial function
of C3d. Wilson worked carefully and systematically in performing his calculations with the help
of graduate student Ron Gorham, and exhibited early evidence of independent thinking. As a
junior, Wilson insisted on taking my senior-level class “Biophysics and Thermodynamics” to
prepare himself for research in my lab. His performance in this demanding class was excellent.
Wilson presented a research poster at the 2012 Southern California Undergraduate Research
Conference in Chemistry and Biochemistry at Cal State University, Channel Islands, and gave
an oral presentation at the 2012 UCR Symposium for Undergraduate Research, Scholarship, and
Creative Activity. After successful submission of an Abstract of his work, he is scheduled for an
oral presentation at the UC Systemwide Bioengineering Symposium at UC Berkeley. Wilson will
continue working on the same project until his graduation.
A U T H O R
Wilson Rodriguez
Bioengineering
Wilson Rodriguez is a junior in
Bioengineering. He is a member
of the student chapter of the
Biomedical Engineering Society
and a member of the Society of
Hispanic Professional Engineers. He
joined the BioMolecular Modeling
and Design Lab (BioMoDeL), led
by Professor Dimitrios Morikis, in
his sophomore year. Interested in
the drug development aspect of
bioengineering, it was when he
spoke with Dr. Morikis about rational
drug design that he knew it was
something he wanted to pursue. His
research focused on the bacterium
Staphylococcus aureus, and the
study of the mechanism by which it
evades our immune system through
the use of small proteins. Atomiclevel
analysis of the non-covalent
forces involved in binding and
stability is useful in the design of
novel therapeutics for treatment. He
plans to pursue a Masters degree
in Bioengineering and a career in
industry.
U C R U n d e r g r a d u a t e R e s e a r c h J o u r n a l 2 3