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Minute Additions of DMSO Affect Protein Dynamics Measurements by NMR Relaxation Experiments through Significant Changes in Solvent Viscosity
Author(s) -
Wallerstein Johan,
Akke Mikael
Publication year - 2019
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.201800626
Subject(s) - chemistry , dimethyl sulfoxide , relaxation (psychology) , ligand (biochemistry) , aqueous solution , solvent , viscosity , diffusion , dissolution , rotational diffusion , rotational correlation time , solubility , protein dynamics , analytical chemistry (journal) , molecular dynamics , computational chemistry , chromatography , organic chemistry , molecule , thermodynamics , psychology , social psychology , biochemistry , physics , receptor
Studies of protein−ligand binding often rely on dissolving the ligand in dimethyl sulfoxide (DMSO) to achieve sufficient solubility, and then titrating the ligand solution into the protein solution. As a result, the final protein−ligand solution contains small amounts of DMSO in the buffer. Here we report how the addition of DMSO impacts studies of protein conformational dynamics. We used 15 N NMR relaxation to compare the rotational diffusion correlation time ( τ C ) of proteins in aqueous buffer with and without DMSO. We found that τ C scales with the viscosity of the water−DMSO mixture, which depends sensitively on the amount of DMSO and varies by a factor of 2 across the relevant concentration range. NMR relaxation studies of side chains dynamics are commonly interpreted using τ C as a fixed parameter, obtained from backbone 15 N relaxation data acquired on a separate sample. Model‐free calculations show that errors in τ C , arising from mismatched DMSO concentration between samples, lead to significant errors in order parameters. Our results highlight the importance of determining τ C for each sample or carefully matching the DMSO concentrations between samples.