Localized and Collective Motions in HET‐s(218‐289) Fibrils from Combined NMR Relaxation and MD Simulation. Issue 28 (5th June 2019)

• Record Type: Journal Article
• Authors: Smith, Albert A.; Ernst, Matthias; Riniker, Sereina; Meier, Beat H.
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 28(2019)
• Page Start: 9383
• Page End: 9388
• Publication Date: 2019-06-05
• Subjects: correlation time -- cross-correlation -- dynamics detector -- molecular dynamics -- NMR relaxation; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201901929
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Nuclear magnetic resonance (NMR) relaxation data and molecular dynamics (MD) simulations are combined to characterize the dynamics of the fungal prion HET‐s(218‐289) in its amyloid form. NMR data is analyzed with the dynamics detector method, which yields timescale‐specific information. An analogous analysis is performed on MD trajectories. Because specific MD predictions can be verified as agreeing with the NMR data, MD was used for further interpretation of NMR results: for the different timescales, cross‐correlation coefficients were derived to quantify the correlation of the motion between different residues. Short timescales are the result of very local motions, while longer timescales are found for longer‐range correlated motion. Similar trends on ns‐ and μs‐timescales suggest that μs motion in fibrils is the result of motion correlated over many fibril layers. Abstract : NMR relaxation yields information on protein dynamics. To perform quantitative and timescale‐specific analysis of NMR relaxation and compare to dynamics from an MD trajectory, the detector method of analysis is applied to HET‐s(218‐289) fibrils. The combined approach yields information neither of the approaches can provide alone.