Chemistry

Proteins are the “work horses” of cells in organisms. They are responsible for muscle contractions, catalyzing chemical reactions in the body, storing nutrients, and most other bodily functions. The S100B protein has functions in cell growth. Consequently, the overexpression of S100B is a biomarker of stage and type of cancers. This means that too much S100B in an organism can indicate that they may have cancer. For S100B to work, the protein must bind to a calcium ion (Ca2+) and a physiological target (a short protein). A prominent characteristic of S100B is its sequential binding: first, S100B binds to Ca2+, then binds to the physiological target, and finally the protein is functional (Figure 1). The Ca2+ binds into a pocket of S100B that is called the EF-hand. The EF-hand is a sequence of twelve amino acids (building blocks of proteins) that help maintain Ca2+ in the pocket. The physiological target binds into a “hydrophobic pocket” of S100B. S100B binds Ca2+ much tighter if the physiological target is available for binding in high concentrations. However, the mechanism of this binding phenomenon is unknown. What specific amino acids of the EF-hand are involved? How do these amino acids behave? Computational chemistry is a rising field in chemistry that can help us answer these questions. By modeling the S100B protein in its natural environment on the computer, we can compute and predict the movements of amino acids using a method called molecular dynamics. We seek to model the S100B protein with and without Ca2+ and with and without physiological target in order to elucidate the binding mechanism.

My research assistant will have successfully modeled the protein system, run molecular dynamics on the system, and collected some structural data on the system. Broadly, the research assistant should conclude feeling confident in their use of basic computational chemistry skills, such as Linux, bash scripting, preparing a biological system, and data collection. They will also practice transferrable skills such as communication (reading literature and presenting data), lab bookkeeping, and how to creatively approach problems.