Significance of Knotted Structures for Function of Proteins and Nucleic Acids
Thursday Abstracts
Connecting Simplified Models with Explicit-Solvent Forcefields: Slipknotting during the
Folding of the Smallest Knotted Protein
Jeffrey Noel
1
, Jose Onuchic
1
, Joanna Sulkowska
2
.
1
Rice University, Houston, USA,
2
University of Warsaw, Warsaw, Poland.
Recently, experiments have confirmed that trefoil knotted proteins can fold spontaneously,
consistent with predictions from simulations of simplified protein models. These simulations
suggest folding the knot involves threading the protein terminal across a twisted loop via a
slipknot configuration. Here, we report unbiased all-atom explicit-solvent simulations of the
knotting dynamics of a protein. In simulations totaling 40 μs, we find that 5 out of 15 simulations
reach the knotted native state when initiated from unknotted, slipknotted, post-transition-state
(post-TS) intermediates. The completed threading events had durations of 0.1− 2 μs. On the μs
timescale, post-TS structures rarely backtracked and pre-TS structures often backtracked and
never completed. Comparison of explicit-solvent to structure-based simulations shows that
similar native contacts are responsible for threading the slipknot through the loop; however,
competition between native and non-native salt bridges during threading results in increased
energetic roughness. Overall, these simulations support a slipknotting mechanism for proteins
with complex topology, and help verify that simplified models are useful tools for studying
knotted proteins.
Significance, Complexity, and Beauty of Knot-avoiding Structures
Alexander Grosberg
.
New York University, New York, USA.
If a long polymer is forced to collapse while remaining unknotted, it adopts a peculiar structure
which is very different from regular conformations where the amount of knots is consistent with
thermodynamic equilibrium. These structures are hypothesized to play an important role in
genome folding across biological realms. Their importance for proteins is an interesting subject
of discussion. Present understanding of these unknotted structures is incomplete, despite
significant efforts in both computer simulations and theoretical estimates. In present work, the
scaling properties of unknotted globules will be discussed, with focus on finite size corrections to
scaling, including new results on contact and surface roughbness exponents. The conclusion of
this work is that forced lack of knots is at least equally important to the actual presence of knots.
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