Sørensen, Jesper4; Hamelberg, Donald3; McCammon, J. Andrew3
1 Department of Chemistry, Faculty of Science, Aarhus University, Aarhus University2 Department of Chemistry, Science and Technology, Aarhus University3 Department of Chemistry & Biochemistry, University of California, San Diego4 Department of Chemistry, Science and Technology, Aarhus University
Providing insight into the misfolding pathway
Many questions about the nature of aggregation and the proteins that are involved in these events are still left unanswered. One of the proteins that is known to form amyloids is Transthyretine (TTR), the secondary transporter of thyroxine and transporter of retinol-binding-protein. Several experimental results have helped to explain this aberrant behavior of TTR, however, structural insights of the amyloidgenic process are still lacking. Therefore, we have used all-atom molecular dynamics simulation and free energy calculations to study the initial phase of this process. We have calculated the free energy changes of the initial tetramer dissociation under different conditions and in the presence of thyroxine.