(192x) Studying the Structure and Dynamics of Amyloid?(21?30) with Experiments and Simulations  | AIChE

(192x) Studying the Structure and Dynamics of Amyloid?(21?30) with Experiments and Simulations 


Amirkulova, D. - Presenter, University of Rochester
White, A., University of Rochester
Chakraborty, M., University of Rochester
Studying the Structure and Dynamics of Amyloidβ21−30 with Experiments and Simulations

Amyloid peptide, Aβ42, is a 42 amino acids long biomolecule that is found in amyloid fibrils and plaques in the brain tissue of patients suffering from Alzheimer’s disease or cerebrovascular disease cerebral amyloid angiopathy [1]. Aβ42 has a 10 residue long, protease and temperature denaturation resistant region called Aβ21−10, which is also known to be a nucleation site for aggregation of Aβ42 to mature plaques [2]. Experiment Directed Simulations (EDS) was used to bias Molecular Dynamics simulations with experimental NMR backbone chemical shifts [3]. EDS biases the simulation by match- ing the ensemble average of a collective variable (a variable that depends on atomic positions) with experimentally observed values of the same variable [3]. EDS provides a constant minimal bias without the use of replicas so that dynamic properties can be studied [3]. During the simulation, Nuclear Overhauser Effect Spectroscopy spectrum was also generated. The poten- tial of mean force was studied for a few collective variables. The dynamics and transitions between different low energy conformations of Aβ21−10 were thoroughly studied with EDS. EDS can be applied to small dynamic biomolecules such as peptides, to study their conformational space as well as their dynamics which are hard to pinpoint experimentally. EDS gives an opportunity to use experimental data with simulations to study microscopic and transient processes that are hard to grasp with just experiments alone.


[1] C. R. Watts. et al, “Structural Properties of Amyloid β(1-40) Dimer Explored by Replica Exchange Molecular Dynamics Simulations,” Proteins, 2017.

[2] M. M. Murray. et al, “Amyloid beta-protein: experiment and theory on the 21-30 fragment.,” J. Phys. Chem.B, 2009.

[3] A. D. White. et al, “Efficient and Minimal Method to Bias Molecular Simulations with Experimental Data,” J. Chem. Theory Comput., 2014.