In a paper published this week in Angewandte Chemie, Professor Steve Homans from Leeds’ Faculty of Biological Sciences explains his method for getting exactly the right molecule first time, by looking not just at the physical shape required to fit the target protein but also at the complex dynamics of the interaction.
Almost everything in the body – including diseases – is a result of a protein binding with another molecule, known as a ligand. Most drug treatments work by blocking this process with another molecule, which takes the place of the natural ligand. Because the binding process is still only partly understood, drug companies currently have to search through millions of possible candidates to find the right ‘fit’, a process which is both time-consuming and costly.
Professor Homans explains: “In the past, scientists have tended to look at the protein ligand interaction like a lock and key – as if the protein is a fixed shape into which the ligand fits. In reality, it’s more like a hand and glove, where you can’t see the real shape of the glove until the hand is inside it. Proteins are very dynamic and the movement that takes place during the interaction with the ligand is an important factor in the binding process.”
“Another key factor is the action of the water molecules in the solution which surrounds the protein. The problem in drug design is knowing to what extent all these factors are influencing the binding process.”
For the first time, Professor Homans’ team have found a way to put a number on how important these different factors are to a protein interaction. They believe that – if their method holds true for all proteins – it will be possible to compute these figures to identify a ligand that is a perfect fit. Ideally, they want to find or create one which will bind more tightly to the protein than its natural counterpart and so act as an effective treatment by fully blocking the target interaction.
The research was done using a multidisciplinary approach including nuclear magnetic resonance (NMR) and protein crystallography. From the NMR data, the team were able to create a computer simulation of the dynamic protein interaction. Professor Homans now plans to test this process using a real target protein for disease – HIV.
“Scientists have known for many years that protein, ligand and water all play a part in the protein interaction, but there has always been intense debate about the contribution each makes. We believe we’ve finally answered that question and opened up a potentially cheaper and more effective avenue for drug design,” he said.
Abigail Chard | alfa
Hunting pathogens at full force
22.03.2017 | Helmholtz-Zentrum für Infektionsforschung
A 155 carat diamond with 92 mm diameter
22.03.2017 | Universität Augsburg
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
22.03.2017 | Materials Sciences
22.03.2017 | Physics and Astronomy
22.03.2017 | Materials Sciences