The transport of oxygen in blood is undertaken by hemoglobin, the largest component of red blood cells. This protein collects oxygen in respiratory organs, mainly in the lungs, and releases it in tissues in order to generate the energy necessary for cell survival. Hemoglobin is one of the most refined proteins because its evolution and small mutations in its structure can produce anaemia and other severe pathologies.
The investigation led by Víctor Guallar, ICREA researcher with the Life Sciences department of the Barcelona Supecomputing Center (BSC) and group leader of the Joint Computational Biology Programme between the Institute for Research in Biomedicine (IRB Barcelona) and the BSC, has allowed the definition at atomic level of the mechanism that regulates the exchange of lung oxygen to hemoglobin and from hemoglobin to tissue. The results of this study are published in the journal Proceedings of the National Academy of Sciences.
More than a hundred years of study have led to the knowledge that hemoglobin uses mechanisms of cooperativity to optimize its function; that is to say, to collect the greatest amount of oxygen possible in the lungs and release it in tissues. These mechanisms of cooperativity are related to changes in the structure of the hemoglobin protein. However, due to the complexity of the system, until now it has not been possible to determine the microscopic mechanisms that guide this process. Consequently, this lack of information has been a serious limitation in drug design and the development of artificial forms that are more effective than the protein.
Víctor Guallar explains that "this study has provided detailed knowledge of the mechanisms that regulate the affinity of hemoglobin, which is crucial to understand, for example, the effects caused by mutations on its structure. Thus, we have obtained basic data on the relation between mutation and disease, which will allow the development of more specific treatments".
Using sophisticated atomic calculation techniques, which combine quantum and classical mechanics, Guallar’s team has determined how, against what was commonly accepted, the affinity for oxygen appears to be controlled by interactions that are relatively distant from the active centre of the protein and that are directly involved in the structural changes responsible for cooperativity. Raúl Alcantara, first author of the study and a member of Guallar’s group points out that "having access to the enormous calculation capacity of the MaresNostrum supercomputer allows more precise simulations, which are closer to what happens in real life".
The results of this study open up vast possibilities for the engineering of this crucial protein. Having identified the factors that regulate the affinity of hemoglobin, alterations of its structure can now be designed. Likewise, the microscopic knowledge about the mechanisms of action of haemoglobin will improve our understanding of the effects of diverse mutations of this protein.
Sonia Armengou | EurekAlert!
Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel
Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
25.05.2018 | Event News
02.05.2018 | Event News
13.04.2018 | Event News
25.05.2018 | Event News
25.05.2018 | Machine Engineering
25.05.2018 | Life Sciences