Title

Analyzing Proteins of the BCL-2 Domain

Poster Number

12B

Lead Author Major

Biological Sciences

Lead Author Status

Junior

Second Author Major

Junior in High School

Format

Poster Presentation

Faculty Mentor Name

Jerry Tsai

Faculty Mentor Email

jtsai@pacific.edu

Faculty Mentor Department

Chemistry

Graduate Student Mentor Name

Shivarni Patel

Graduate Student Mentor Email

s_patel18@u.pacific.edu

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

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Apr 29th, 1:00 PM Apr 29th, 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.