A powerful new way of analysing how drugs interact with molecules in the body could aid the design of better treatments with fewer side-effects.
Most pharmaceuticals work by binding to a small site on the large proteins they target, causing the protein to change shape and so also its activity.
To find drugs that act specifically against a protein without also binding to others that are similar – and so causing side effects – it is important to understand this binding site in detail. Many current techniques can only provide partial information, giving details about which parts of the drug itself are important and, in some cases, the overall structure of the protein.
Researchers at the University of East Anglia have now developed a new approach that can reveal the other side of the jigsaw puzzle – which parts of the protein interact with the drug. It adapts a technique known as ligand-based Nuclear Magnetic Resonance (NMR) spectroscopy to reveal which amino acids in the protein are involved in binding to the drug.
They were able to do this by examining the drug and without having to label the protein, as is required in some other methods.
“Designing novel drugs is a bit like finding the proper piece that fits into a jigsaw puzzle,” said Dr Jesus Angulo, a senior lecturer at the University of East Anglia’s school of pharmacy who led the research. “It is not just the shape but also graphical content on the piece that must match the surrounding picture.
“Our novel approach allows us to now find the exact piece that matches the complementary shape and graphical content in a protein binding site.”