Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue

The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. We developed and validated a novel method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and used solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise a mixture of single protofilament and two protofilament fibrils with very low twist. The protofilament fold is highly similar to the fold determined by a recent cryo-electron microscopy study for a minority population of twisted single protofilament fibrils extracted from LBD tissue. These results expand the structural characterization of LBD Asyn fibrils and enable new approaches for studies of disease mechanisms, imaging agents and therapeutics targeting Asyn., , , # Structure of Alpha-Synuclein Fibrils Derived from Human Lewy Body Dementia Tissue

[https://doi.org/10.5061/dryad.tx95x6b4z](https://doi.org/10.5061/dryad.tx95x6b4z)

## Description of the data and file structure

### **Dryad**

File 1: 0to200ns_traj.dcd

An all-atom MD simulation of a two-fold symmetric Asyn fibril (2x20-mer) was performed using NAMD 3.0[.](#_ENREF_97) The CHARMM36m protein force field was applied to the fibrils. We simulated the fibril in an explicit water box of size 180 x 100 x 180 Å3 with an ion concentration of 0.15 M (NaCl solution) using an NPT ensemble with N = 306450, P = 1.01325 bar and T = 310 K. The system was subjected to Langevin dynamics with damping constant γ = 1.0 ps^-1 and the Nosé-Hoover Langevin piston method was employed to maintain constant pressure. The MD integration time step was set to 2 fs. To evaluate long range electrostatic interactions, particle mesh Ewald was used in the presence of periodic boundary conditions. Non-bonded van der Waa...