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Understanding epigenetics to develop new therapies

Conquest - Fall 2013

Revealing structural insights

By Hilary Graham

Structural biologists work at the intersection of biology and chemistry, as they determine the physical structure of proteins. The IACS collaboration with Ladbury and Poncet-Montange has enabled the project to progress rapidly, as they provide critical insights on how IACS’ small molecules bind to drug targets.

John Ladbury, Ph.D., and Guillaume Poncet-Montange, Ph.D.
crystalize proteins, such as TRIM24 (green), in complex with 
small molecules or biological binding partners. In turn, these 
solved structures guide the chemists in their design of small 
molecules with improved properties.
Photo: Wyatt McSpadden

To determine the structure of a protein, it must first be crystallized, which is no easy task. Often thousands of conditions must be tested before crystals form. These crystals are then soaked with the drug of interest. The samples are then bombarded with high-speed X-rays that give rise to unique diffraction patterns. Sophisticated computer algorithms then allow the three-dimensional protein structure to be solved, thereby revealing how the drug binds.

Ladbury and Poncet-Montange have solved more than 50 proprietary drug-bound structures to date.

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