Molecular Visualization

ATR-inhibitor

 

Designed for an educated lay audience, this molecular illustration shows the biomolecular structure, function, and mechanism of action (MOA) of a promising cancer suppressor, VS-970.

STORY

DNA-damaging agents are a cornerstone of cancer treatment. However, their effectiveness is limited by the DNA-damage response in cancer cells. ATR, a protein kinase, is a critical regulator of this DNA repair pathway and is a novel therapeutic target for drug design.

 

I created this two-page spread for a popular science magazine to illustrate the mechanism of action for VX-970, an ATR-inhibitor and cancer suppressor. I summarized ATR suppression into five steps showing the mechanism at both microscopic and molecular levels. A combination of colour-coding scheme, depth of field, and simplicity in background design were used to enhance communication clarity.

DESCRIPTION

Year

July.2018

Course

Biomolecular Visualization

Client

Derek Ng

Audience

Educated lay audience

Format

Print, Magazine

two-page spread

Medium

UCSF Chimera
Maxon Cinema4D
Adobe Photoshop
Adobe Illustrator

01

Media Audit

Preliminary research

PROCESS WORK

02

Ideate &

Sketches

03

Research

Identify

Knowledge Gap

Production

04

REFERENCE

Burgers, P. M., & Kunkel, T. A. (2017). Eukaryotic DNA replication
fork. Annual review of biochemistry, 86, 417-438.

Stillman, B. (2008). DNA polymerases at the replication fork in
eukaryotes. Molecular cell, 30(3), 259-260.

Stephen P. Bell (MIT / HHMI) 1b: Chromosomal DNA
Replication: Initiation of DNA Replication
https://www.youtube.com/watch?v=sxedBRA18Ro&t=616s

Georgescu, R., Yuan, Z., Bai, L., Santos, R. D. L. A., Sun, J., Zhang, D., ... &
O’Donnell, M. E. (2017). Structure of eukaryotic CMG helicase at a
replication fork and implications to replisome architecture and origin
initiation. Proceedings of the National Academy of Sciences, 114(5), E697-
E706.
 

Wallen, J. R., Zhang, H., Weis, C., Cui, W., Foster, B. M., Ho, C. M., ... &
Ellenberger, T. (2017). Hybrid methods reveal multiple flexibly linked DNA
polymerases within the bacteriophage T7 replisome. Structure, 25(1), 157-
166.
 

Sun, J., Shi, Y., Georgescu, R. E., Yuan, Z., Chait, B. T., Li, H., &
O'donnell, M. E. (2015). The architecture of a eukaryotic
replisome. Nature Structural and Molecular Biology, 22(12), 976.

Fan, J., & Pavletich, N. P. (2012). Structure and conformational change of areplication protein A heterotrimer bound to ssDNA. Genes &development, 26(20), 2337-2347.

Bochkarev, A., Pfuetzner, R. A., Edwards, A. M., & Frappier, L. (1997).
Structure of the single-stranded-DNA-binding domain of replication
protein A bound to DNA. Nature, 385(6612), 176.
 

Rao, Q., Liu, M., Tian, Y., Wu, Z., Hao, Y., Song, L., ... & Xu, Y. (2018).
Cryo-EM structure of human ATR-ATRIP complex. Cell research, 28(2),
143.

 

Hall, A. B., Newsome, D., Wang, Y., Boucher, D. M., Eustace, B., Gu, Y., ... & Takemoto, D. (2014). Potentiation of tumor responses to DNA damaging
therapy by the selective ATR inhibitor VX-970. Oncotarget, 5(14), 5674.

 

Rao, Q., Liu, M., Tian, Y., Wu, Z., Hao, Y., Song, L., ... & Xu, Y. (2018).
Cryo-EM structure of human ATR-ATRIP complex. Cell research, 28(2),
143.

 

Lu, Y., Knapp, M., Crawford, K., Warne, R., Elling, R., Yan, K., ... &
Mamo, M. (2017). Rationally designed PI3Kα mutants to mimic ATR
and their use to understand binding specificity of ATR
inhibitors. Journal of molecular biology, 429(11), 1684-1704. 2.
 

Vendetti, F. P., Lau, A., Schamus, S., Conrads, T. P., O'Connor, M. J., &
Bakkenist, C. J. (2015). The orally active and bioavailable ATR kinase
inhibitor AZD6738 potentiates the anti-tumor effects of cisplatin to
resolve ATM-deficient non-small cell lung cancer in
vivo. Oncotarget, 6(42), 44289.

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