Identified protein-ligand binding could contribute to early detection of Alzheimer’s disease
Researchers at the department Theoretical Chemistry and Biology have contributed to the understanding of the interaction between markers and the proteins behind Alzheimer’s disease.
In Alzheimer’s disease as well as in another form of dementia known as Pick’s disease, changes occur in proteins in the patient’s brain so that the proteins fold in an abnormal way. The proteins of main importance are proteins of the types amyloid beta and tau.
”There is an incorrect folding which causes the proteins to aggregate and form long fibrils”, says Patrick Norman, professor in Theoretical chemistry.
The proteins form plaques in the brain that eventually cause the death of brain cells.
Using advanced computer simulations, the researchers have been able to identify where the ligand binds to the misfolded tau protein in Alzheimer’s disease. The results have recently been published in the scientific journal The Journal of Physical Chemistry B, and doctoral student Yogesh Todarwal is first author of the article.
”Our work will contribute to increased future opportunities to probe and learn more about the aggregates of misfolded proteins that underlie the disease”, says Yogesh Todarwal.
The ligand belongs to a category of luminescent conjugated oligothiophenes and has been developed in collaboration with researchers at Linköping University under the direction of professor Peter Nilsson.
“The protein-ligand binding has been mapped to a site of the folded protein which is exposed in Alzheimer’s disease but not in other disease forms, which explains the specificity of the ligand”, says Patrick Norman.
“What we are onto is to steer the binding of the ligand by means of chemical design”, he continues.
The molecular dynamics simulations have been carried out at the PDC Center for High Performance Computing at KTH.
"A system containing 3.4 million atoms was simulated using millions of computer core hours. Without the access to supercomputers, such as the Dardel parallel cluster at PDC/KTH, it would have been impossible to finish the project in the time frame of my Ph.D.”, says Yogesh Todarwal.
What can this research be used for?
”It is about increased basic understanding and early-stage detection. As of today, these diseases are incurable, but the genesis occur some 10-15 years before you can see clinical symptoms. Our aim is to enable the possibility of slowing down the course of the disease at an early stage”, Patrick Norman says.
Text: Sabina Fabrizi
Read more: “Tau Protein Binding Modes in Alzheimer's Disease for Cationic Luminescent Ligands”(diva2:1617153)