In this review, we provide an overview of entangled proteins. Around 6% of protein structures deposited in the PBD are entangled, forming knots, slipknots, lassos and links. We present theoretical methods and tools that enabled discovering and classifying such structures. We discuss the advantages and disadvantages of the non-trivial topology in proteins, based on available data about folding, stability, biological properties and evolutionary conservation. We also formulate intriguing and challenging questions on the border of biophysics, bioinformatics, biology and mathematics, which arise from the discovery of an entanglement in proteins. Finally, we discuss possible applications of entangled proteins in medicine and nanotechnology, such as the chance to design super stable proteins, whose stability could be controlled by chemical potential.
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