There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
<p class="first" id="P5">It is widely accepted that structural rigidity is required
to achieve high levels
of asymmetric induction in catalytic, enantioselective reactions. This fundamental
design principle often does not apply to highly selective catalytic peptides that
often exhibit conformational heterogeneity. As a result, these complex systems are
particularly challenging to study both experimentally and computationally. Herein,
we utilize molecular dynamics simulations to investigate the role of conformational
mobility on the reactivity and selectivity exhibited by a catalytic, β-turn-biased
peptide in an atroposelective bromination reaction. By means of cluster analysis,
multiple distinct conformers of the peptide and a catalyst-substrate complex were
identified in the simulations, all of which were corroborated by experimental NMR
measurements. The simulations also revealed that a shift in the conformational equilibrium
of the peptidic catalyst occurs upon addition of substrate, and the degree of change
varies among different substrates. On the basis of these data, we propose a correlation
between the composition of the peptide conformational ensemble and its catalytic properties.
Moreover, these findings highlight the importance of conformational dynamics in catalytic,
asymmetric reactions mediated by oligopeptides, unveiled through high-level, state-of-the-art
computational modeling.
</p><p id="P6">
<div class="figure-container so-text-align-c">
<img alt="" class="figure" src="/document_file/a68d5c71-84c1-4fe6-ad32-655a87c38ee0/PubMedCentral/image/nihms-989993-f0001.jpg"/>
</div>
</p>