Journal
CHEMPHYSCHEM
Volume 22, Issue 1, Pages 18-28Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cphc.202000789
Keywords
cross-correlated relaxation; NMR spectroscopy; protein dynamics; protein structures; statistical inference
Funding
- Austrian Science Fund FWF [P28359, P28937]
- FWF Lise-Meitner Postdoctoral Fellowship [M 2084]
- Austrian Science Fund (FWF) [P28359, P28937] Funding Source: Austrian Science Fund (FWF)
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The study demonstrates that using a modern MaxEnt reweighting approach to interpret CCR rates of Ubiquitin can resolve CCR-encoded structural information despite uncertainties. A suitable balance between complementary CCR experiments and prior information is crucial in mapping backbone dihedral angle distributions. Using Ubiquitin as an example, the CCR rates are capable of characterizing both rigid and flexible residues, indicating their potential in studying disordered proteins.
Crucial to the function of proteins is their existence as conformational ensembles sampling numerous and structurally diverse substates. Despite this widely accepted notion there is still a high demand for meaningful and reliable approaches to characterize protein ensembles in solution. As it is usually conducted in solution, NMR spectroscopy offers unique possibilities to address this challenge. Particularly, cross-correlated relaxation (CCR) effects have long been established to encode both protein structure and dynamics in a compelling manner. However, this wealth of information often limits their use in practice as structure and dynamics might prove difficult to disentangle. Using a modern Maximum Entropy (MaxEnt) reweighting approach to interpret CCR rates of Ubiquitin, we demonstrate that these uncertainties do not necessarily impair resolving CCR-encoded structural information. Instead, a suitable balance between complementary CCR experiments and prior information is found to be the most crucial factor in mapping backbone dihedral angle distributions. Experimental and systematic deviations such as oversimplified dynamics appear to be of minor importance. Using Ubiquitin as an example, we demonstrate that CCR rates are capable of characterizing rigid and flexible residues alike, indicating their unharnessed potential in studying disordered proteins.
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