Scientists at Sanford-Burnham Medical Research Institute (Sanford-Burnham) are collaborating with scientists and software developers at MEDIT SA in France to use and enhance a new software platform built around a computer program called MED-SuMo. This platform searches protein structure databases to find compounds that bind to a particular target, and then helps optimize these “hits” to design new drugs.
“We believe that this collaboration with MEDIT significantly enhances our ability to perform structure-based drug design,” said Nicholas Cosford, Ph.D. associate professor in the Apoptosis and Cell Death Research Program in Sanford-Burnham’s Cancer Center and leader of the collaborative team. “MEDIT’s MED-SuMo software offers unique capabilities that will complement drug discovery platforms already being used in the Conrad Prebys Center for Chemical Genomics [CPCCG] at Sanford-Burnham.”
Here’s how the MEDIT technology works: Sanford-Burnham researchers select a protein they wish to target. Let’s say that this protein, Protein X, normally tells cells to divide, but when it malfunctions, it causes unchecked cell division that leads to a tumor. In an effort to uncover new anti-cancer drugs, scientists want to find compounds that bind to the deviant Protein X and turn it off. Normally, it might take months or years of work and a stroke of luck to find the one needle-in-a-haystack compound that binds and inhibits Protein X without interfering with other proteins.
Dr. Cosford and his team are taking a more targeted approach to drug design with MEDIT’s software platform. MED-SuMo takes a 3D model of Protein X and breaks it down into pieces. Then the software digs through a publically available database containing more than 60,000 proteins with known structures to find “hits” – pieces that structurally resemble parts of Protein X, but are already known to bind certain compounds. MED-SuMo superimposes the matching hits on the structure of Protein X, allowing researchers to see a 3D image of the interaction. Chemical fragments bound to the hits will bind to Protein X in a similar fashion, forming the initial building blocks for a new drug.
Once MED-SuMo puts these pieces together, MEDIT technology takes drug design several steps further. Another program, called MED-Ligand, can optimize multiple hits by finding ways they could be combined to form a single hybrid drug compound that binds Protein X better and more selectively. The system can even screen out any combinations that couldn’t realistically be generated by chemists in the laboratory, as well as those that might harm other proteins or cause toxicity in humans.
“We’re using MEDIT’s software to look for highly effective drugs,” explained Peter Teriete, Ph.D., post-doctoral researcher in Dr. Cosford’s group. “The great thing about using MED-SuMo at Sanford-Burnham is that we’re also surrounded by drug discovery experts. So if I find something that looks good on the computer, I can work with chemists and assay developers to synthesize the compound in the lab and test it to determine whether or not it has the potential to become a new drug.”
The collaboration goes both ways – Dr. Teriete and others benefit from the software and MEDIT SA’s engineers benefit from their feedback on what works, what could work better, and what additional features would be helpful. Their ideas and experiences will enrich future versions of the MEDIT technology platform, making it an even more powerful tool for drug discovery.
“This agreement with Sanford-Burnham, a leading scientific institution in the U.S., is a great opportunity for our company,” said Stephane Richard, Ph.D., vice president of business development at MEDIT SA. “The collaborative nature of the deal and the involvement of our technology in a number of structure-based drug design efforts will allow researchers at Sanford-Burnham to capitalize on our scientists’ expertise in this field.”