TO KNOT OR NOT TO KNOT: SLIPKNOTTING IN THE SMALLEST KNOTTED PROTEIN

Carnegie-Mellon University, Pittsburgh PA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The discovery of proteins with knots has challenged our preconceptions about viable protein structures and could modify protein folding theory. Extensive experimental studies have shown that knotted proteins can be easily folded from pre-knotted conformations. However, since they cannot distinguish between knotted and unknotted structures, interpretation of the data is impossible. The full folding mechanism has recently been proposed theoretically based on simplified folding models, but these simulations still do not explain the origin of the driving force for knotting. The goal of this work is to understand in detail the threading mechanism by performing a long MD simulation.