Joshua Ward - Microsecond Time-Scale Conformational Exchange in Proteins: Using Long Molecular Dynamics Trajectory To Simulate NMR Relaxation Dispersion Data

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      Publication Details (including relevant citation   information):

        Yi Xue, Joshua M. Ward,   Tairan Yuwen, Ivan S. Podkorytov,   and Nikolai R. Skrynnikov;   J. Am. Chem. Soc.,   2012, Article ASAP,   December 29, 2011


        With the advent of ultra-long MD simulations it becomes possible   to model microsecond time-scale protein dynamics and, in   particular, the exchange broadening effects (Rex)   as probed by NMR relaxation dispersion measurements. This new   approach allows one to identify the exchanging species, including   the elusive “excited states”. It further helps to map out the   exchange network, which is potentially far more complex than the   commonly assumed 2- or 3-site schemes. Under fast exchange   conditions, this method can be useful for separating the   populations of exchanging species from their respective chemical   shift differences, thus paving the way for structural analyses.   In this study, recent millisecond-long MD trajectory of protein   BPTI (Shaw et al.   Science2010,    330,   341) is employed to simulate the time variation of   amide15N   chemical shifts. The results are used to predict the exchange   broadening of   15N   lines and, more generally, the outcome of the relaxation   dispersion measurements using Carr–Purcell–Meiboom–Gill sequence.   The simulated   Rex    effect stems from the fast (10–100   μs) isomerization of the C14–C38 disulfide bond, in agreement   with the prior experimental findings (Grey et al.    J. Am. Chem. Soc.2003,    125,   14324).

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