Analyzing Proteins of the BCL-2 Domain
Poster Number
12B
Format
Poster Presentation
Faculty Mentor Name
Jerry Tsai
Faculty Mentor Department
Chemistry
Graduate Student Mentor Name
Shivarni Patel
Graduate Student Mentor Department
Chemistry
Abstract/Artist Statement
Cancer has been a pervasive and deadly problem for many years. So far, no treatments have been developed that effectively destroy cancer cells while also keeping healthy cells safe. Our goal is to use a knob-socket analysis of protein quaternary packing structure to map the key protein interactions between a cancer protein and its ligand. This mapping allows us to identify the quaternary amino acid interactions that define ligand specificity and binding strength. From this analysis, an artificial protein mimetic of the binding helix can be developed. Protein mimetics have a similar domain structure, and can bind with pro-apoptotic activators to help destroy cancer cells. In the knob-socket mapped protein-ligand interactions, the helix ligand possesses between 8 to 10 residues that specifically interact with 4 helices of BH3 and BCL-2 interactions. Specifically, the helical ligand interacts with 4 helices on the binding protein: the N terminus of helix 2, the main bodies of helix 3 and helix 4 and the C terminus of helix 5. The analysis has identified the key amino acids important for binding, which can inform the design of potential mimetics that can be cancer therapeutics. Among all of the interactions that were analyzed, there were three amino acids, glycine, leucine, and isoleucine, from the ligand that always pack into the binding protein helices in the hydrophobic groove that is key for ligand recognition. Further analysis involves mapping the important residue interactions important for defining specificity between binding proteins. In this way, the knob-socket analysis can help the development of mimetics that are more effective as treatments.
Location
DeRosa University Center, Ballroom
Start Date
29-4-2017 1:00 PM
End Date
29-4-2017 3:00 PM
Analyzing Proteins of the BCL-2 Domain
DeRosa University Center, Ballroom
Cancer has been a pervasive and deadly problem for many years. So far, no treatments have been developed that effectively destroy cancer cells while also keeping healthy cells safe. Our goal is to use a knob-socket analysis of protein quaternary packing structure to map the key protein interactions between a cancer protein and its ligand. This mapping allows us to identify the quaternary amino acid interactions that define ligand specificity and binding strength. From this analysis, an artificial protein mimetic of the binding helix can be developed. Protein mimetics have a similar domain structure, and can bind with pro-apoptotic activators to help destroy cancer cells. In the knob-socket mapped protein-ligand interactions, the helix ligand possesses between 8 to 10 residues that specifically interact with 4 helices of BH3 and BCL-2 interactions. Specifically, the helical ligand interacts with 4 helices on the binding protein: the N terminus of helix 2, the main bodies of helix 3 and helix 4 and the C terminus of helix 5. The analysis has identified the key amino acids important for binding, which can inform the design of potential mimetics that can be cancer therapeutics. Among all of the interactions that were analyzed, there were three amino acids, glycine, leucine, and isoleucine, from the ligand that always pack into the binding protein helices in the hydrophobic groove that is key for ligand recognition. Further analysis involves mapping the important residue interactions important for defining specificity between binding proteins. In this way, the knob-socket analysis can help the development of mimetics that are more effective as treatments.