The 4 hemo groups of the hemoglobin that are responsible for the
union with oxygen.
� BSC-IRB Barcelona
The molecular structure of the hemoglobin.
� BSC-IRB Barcelona
The investigation led by V�ctor 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.
V�ctor 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. Ra�l 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