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
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences