TY - JOUR T1 - Knotted vs. Unknotted Proteins: Evidence of Knot-Promoting Loops A1 - Potestio, Raffaello A1 - Micheletti, Cristian A1 - Orland, Henri Y1 - 2010/07/29 N2 - Author Summary Out of the tens of thousands of known protein structures, only a few hundred are knotted. The latter epitomize, better than unknotted proteins, the degree of coordinated motion of the backbone required to fold reversibly in a specific native conformation, which indeed must contain a precise knot in a specific protein region. In the present work we search for salient features associated to protein “knottedness” through a systematic sequence and structure comparison of knotted and unknotted protein chains. A significant sequence relatedness is found within a sizeable group of knotted and unknotted proteins. Their tree of sequence relatedness suggests that the knotted entries all diverged from a specific evolutionary event. The systematic structural comparison further indicates that the knottedness of several different types of proteins is likely ascribable to the presence of short “knot-promoting” loops. These segments, whose bridging eliminates the knot, are natural candidates for future experimental/computational studies aimed at clarifying whether the global knotted state of a protein is influenced by specific regions of the primary sequence. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 6 IS - 7 UR - https://doi.org/10.1371/journal.pcbi.1000864 SP - e1000864 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1000864 ER -