
Computational design of trimeric influenza-neutralizing proteins (2017) [pdf] - lawrenceyan
https://www.bakerlab.org/wp-content/uploads/2017/06/Strauch_NatureBiotech_2017.pdf
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lawrenceyan
_A short excerpt of the paper to potentially pique your interest:_

Many viral surface glycoproteins and cell surface receptors are homo-
oligomers, and thus can potentially be targeted by geometrically matched homo-
oligomers that engage all subunits simultaneously to attain high avidity
and/or lock subunits together.

The adaptive immune system cannot generally employ this strategy since the
individual antibody binding sites are not arranged with appropriate geometry
to simultaneously engage multiple sites in a single target homo-oligomer. We
describe a general strategy for the computational design of homo-oligomeric
protein assemblies with binding functionality precisely matched to
homooligomeric target sites. In the first step, a small protein is designed
that binds a single site on the target. In the second step, the designed
protein is assembled into a homo-oligomer such that the designed binding sites
are aligned with the target sites. We use this approach to design high-avidity
trimeric proteins that bind influenza A hemagglutinin (HA) at its conserved
receptor binding site.

The designed trimers can both capture and detect HA in a paper-based
diagnostic format, neutralizes influenza in cell culture, and completely
protects mice when given as a single dose 24 hours before or after challenge
with influenza.

