%0 Journal Article %J Journal of the American Chemical Society %D 2010 %T Untying knots in proteins. %A Joanna I. Sulkowska %A SuĊ‚kowski, Piotr %A Szymczak, Piotr %A Cieplak, Marek %K Amino Acids %K Protein Conformation %K Proteins %X A shoelace can be readily untied by pulling its ends rather than its loops. Attempting to untie a native knot in a protein can also succeed or fail depending on where one pulls. However, thermal fluctuations induced by the surrounding water affect conformations stochastically and may add to the uncertainty of the outcome. When the protein is pulled by the termini, the knot can only get tightened, and any attempt at untying results in failure. We show that, by pulling specific amino acids, one may easily retract a terminal segment of the backbone from the knotting loop and untangle the knot. At still other amino acids, the outcome of pulling can go either way. We study the dependence of the untying probability on the way the protein is grasped, the pulling speed, and the temperature. Elucidation of the mechanisms underlying this dependence is critical for a successful experimental realization of protein knot untying. %B Journal of the American Chemical Society %V 132 %P 13954-6 %8 2010 Oct 13 %G eng %N 40 %R 10.1021/ja102441z %0 Journal Article %J PLoS Comput Biol %D 2009 %T Mechanical strength of 17,134 model proteins and cysteine slipknots. %A Sikora, Mateusz %A Joanna I. Sulkowska %A Cieplak, Marek %K Amino Acids %K Cysteine %K elasticity %K Humans %K Models, Molecular %K Molecular Dynamics Simulation %K Protein Folding %K Proteins %K Tensile Strength %X A new theoretical survey of proteins' resistance to constant speed stretching is performed for a set of 17,134 proteins as described by a structure-based model. The proteins selected have no gaps in their structure determination and consist of no more than 250 amino acids. Our previous studies have dealt with 7510 proteins of no more than 150 amino acids. The proteins are ranked according to the strength of the resistance. Most of the predicted top-strength proteins have not yet been studied experimentally. Architectures and folds which are likely to yield large forces are identified. New types of potent force clamps are discovered. They involve disulphide bridges and, in particular, cysteine slipknots. An effective energy parameter of the model is estimated by comparing the theoretical data on characteristic forces to the corresponding experimental values combined with an extrapolation of the theoretical data to the experimental pulling speeds. These studies provide guidance for future experiments on single molecule manipulation and should lead to selection of proteins for applications. A new class of proteins, involving cysteine slipknots, is identified as one that is expected to lead to the strongest force clamps known. This class is characterized through molecular dynamics simulations. %B PLoS Comput Biol %V 5 %P e1000547 %8 2009 Oct %G eng %N 10 %R 10.1371/journal.pcbi.1000547