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<h1><a href="index.html">NMR TITAN</a></h1>
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<h2>Documentation</h2>
<p>NMR TITAN: 2D lineshape analysis</p>
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<h3>NMR lineshape analysis</h3>
<p><span class="image left"><img src="images/lineshape-landscape.png" alt="" /></span>
NMR titrations are rich in structural and mechanistic detail
about molecular interactions. We have carried out theoretically
rigorous studies of the impact of chemical exchange on common
two-dimensional NMR experiments, culminating in new data analysis
approach termed <i>two-dimensional lineshape analysis</i>.</p>
<p>
We are developing improved acquisition
schemes and easy-to-use analysis methods, including the popular
software package <a href="https://www.nmr-titan.com">NMR TITAN</a>,
to extract the fullest possible information
from your experimental measurements.</p>
<hr />
<h3>NMR dynamics & methodology</h3>
<p><span class="image right"><img src="images/qq.png" alt="" /></span>
We continue to push the capabilities of NMR spectroscopy with the
development of new experiments for the analysis of biomolecular dynamics.
</p>
<p>
Recently, this has included the identification of long-lived high-order coherences
within methyl groups that can be studied to provide sensitive probes of
chemical exchange, improved experimental schemes for the sensitive
measurement of cross-correlated relaxation within low-concentration or unstable
samples such as ribosome-nascent chain complexes, and the application of
optimal design theory to acquire adaptively sampled relaxation measurements.
</p>
<h4>More detail</h4>
<p>Etiam iaculis nulla ipsum, et pharetra libero rhoncus ut. Phasellus rutrum cursus velit, eget condimentum nunc blandit vel. In at pulvinar lectus. Morbi diam ante, vulputate et imperdiet eget, fermentum non dolor. Ut eleifend sagittis tincidunt. Sed viverra commodo mi, ac rhoncus justo. Duis neque ligula, elementum ut enim vel, posuere finibus justo. Vivamus facilisis maximus nibh quis pulvinar. Quisque hendrerit in ipsum id tellus facilisis fermentum. Proin mauris dui, at vestibulum sit amet, auctor bibendum neque.</p> -->
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<h3>Protein folding and misfolding</h3>
<p>
<span class="image left"><img src="images/ribosome-nmr.png" alt="" /></span>
The efficient biosynthesis of proteins, and the subsequent folding to their native
states, is a process of central importance to biology. The failure of proteins to reach
their native structure can result in disorders arising from loss of function, or in
the population of toxic misfolded or aggregated states that are implicated in severe
neurological disorders. The Waudby group is interested in applications of NMR spectroscopy
to provide unique, residue-specific probes of protein structure and dynamics during
protein biosynthesis and folding.
</p>
<p>
During his time in the Christodoulou group at UCL, Chris developed particular
expertise in NMR spectroscopy of co-translational folding within translationally-arrested
ribosome-nascent chain complexes. Co-translational folding is a fundamental
mechanism for ensuring efficient protein biosynthesis, minimising the wasteful or hazardous
formation of misfolded states, but developing a structural understanding of co-translational
folding pathways has been a major experimental challenge. By developing and applying
advanced NMR methods, we have begun to make progress in understanding the evolution
of the free-energy landscape as a nascent chain emerges from the ribosome, and the
major role that interactions between the nascent chain and ribosome surface can have on the
folding process.
</p>
<h4>Ex vivo NMR</h4>
<p>
<span class="image right"><img src="images/ex-vivo.png" alt="" /></span>
α<sub>1</sub>-antitrypsin (α<sub>1</sub>AT) is a 52 kDa serine protease inhibitor found at high
concentrations in human plasma. The Z mutation (E342K) occurs in 1 in 1700 Northern
Europeans and promotes polymerisation leading to liver cirrhosis and early onset emphysema.
Polymerisation is thought to progress from a near native, monomeric species of an unknown
conformation, but a recent crystal structure of the polymerogenic Z variant revealed few
differences to the wild type variant, suggesting that changes in aggregation behaviour
lie with the differences in structural dynamics between variants. To address this we
are using NMR measurements of structure and dynamics to characterise the structure, dynamics
and polymerisation of α<sub>1</sub>AT. We have developed strategies to study
<strong>patient-derived</strong> samples of wild-type and disease-associated α<sub>1</sub>AT
variants using 2D <sup>1</sup>H,<sup>13</sup>C NMR at natural abundance. This provides
access to natively-glycosylated variants that often cannot be expressed recombinantly,
providing important insights into the conformation and dynamics of α<sub>1</sub>AT in solution.
</p>
<hr />
<h3>Collaborations</h3>
<p>We are always happy to work together with other researchers, and have enjoyed a number of successful collaborations with groups around the world, including:</p>
<ul>
<li>Badjic group (Ohio State)</li>
<li>Bellotti group (UCL / Pavia)</li>
<li>Christodoulou group (UCL)</li>
<li>Lomas group (UCL)</li>
<li>Peters group (Lübeck)</li>
<li>Pielak group (UNC Chapel Hill)</li>
<li>Tripsianes group (Brno)</li>
</ul>
<p>Please get in touch if you have a problem you'd like to work together on!</p>
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