Deuteron Quadrupolar Chemical Exchange Saturation Transfer (Q‐CEST) Solid‐State NMR for Static Powder Samples: Approach and Applications to Amyloid‐β Fibrils. Issue 3 (9th January 2020)

• Record Type: Journal Article
• Authors: Vugmeyster, Liliya; Ostrovsky, Dmitry; Fu, Riqiang
• Is Part Of: Chemphyschem. Volume 21:Issue 3(2020)
• Page Start: 220
• Page End: 231
• Publication Date: 2020-01-09
• Subjects: Chemistry, Physical and theoretical -- Periodicals; 541.05
• DOI: 10.1002/cphc.201901053
• Languages: English
• ISSNs: 1439-4235

Abstract

Abstract: We provide an experimental and computational framework for 2 H quadrupolar chemical exchange saturation transfer NMR experiments (Q‐CEST) under static solid‐state conditions for the quantification of dynamics on μs‐ms timescales. Simulations using simple 2‐site exchange models provide insights into the relation between spin dynamics and motions. Biological applications focus on two sites of amyloid‐β fibrils in the 3‐fold symmetric polymorph. The first site, the methyl group of A2 of the disordered N‐terminal domain, undergoes diffusive motions and conformational exchange due to transient interactions. Earlier 2 H rotating frame relaxation and quadrupolar CPMG measurements are combined with the Q‐CEST approach to characterize the multiple conformational states of the domain. The second site, the methyl group of M35, spans the water‐accessible cavity inside the fibrils' core and undergoes extensive rotameric exchange. Q‐CEST permits us to refine the rotameric exchange model for this site and allows the more precise determination of populations and rotameric exchange rate constants than line shape analysis. Abstract : Dynamics vs. motion : We provide an experimental and computational framework for 2 H quadrupolar chemical exchange saturation transfer NMR experiments under static solid‐state conditions for the quantification of dynamics. Simulations using simple 2‐site exchange models provide insights into the relation between spin dynamics and motions. Biological applications are focused on two sites of amyloid‐β fibrils in the 3‐fold symmetric polymorph.