Biomedical Engineering Reference
In-Depth Information
8.5 Conclusions
RDCs provide highly sensitive probes of protein conformation, and over the
last 15 years, have been exploited extensively for their ability to refine protein
solution structures to unprecedented resolution, to provide long-range
information about domain orientations or protein-protein complexes, and
even to determine structures ab initio. However RDCs are also highly sensitive
to conformational dynamics. Despite the sensitivity of all NMR data to
molecular motion, the faithful incorporation of dynamic fluctuations into
structural models of proteins remains a major challenge. Recent development
of methods for measurement and interpretation of RDCs, and their
combination with state-of-the-art MD based approaches, have provided a
powerful combination of techniques to resolve this fundamental question.
The agreement of purely analytical, and purely simulation-based approaches
to the determination of protein motions using RDCs is excellent, providinga
structural dynamic representation of the statistical mechanical properties of a
protein in solution, and describing dynamic fluctuations on a broad range of
timescales. In addition to describing the conformational fluctuations that may
sample the functional states of the protein already in free solution, this
ensemble description describes the origin of the solution-state NMR spectrum,
and this in itself will further our understanding of molecular function and
stability. So far these techniques have been applied to small, well-behaved
proteins that can be aligned in multiple alignment media, and it remains to be
seen how general such approaches can be made.
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