Protein knot server: detection of knots in protein structures

Kolesov, Grigory; Virnau, Peter; Kardar, Mehran; Mirny, Leonid A.

doi:10.1093/nar/gkm312

Cited by 95 publications

(102 citation statements)

References 23 publications

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“…It involves removing the C ␣ atoms, one at a time, as long as the backbone does not intersect a triangle set by the atom under consideration and its 2 immediate sequential neighbors. The knots can be identified also by protein knot server (36).…”

Section: Methodsmentioning

confidence: 99%

Stabilizing effect of knots on proteins

Sułkowska

Sułkowski

Szymczak

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

139

147

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Molecular dynamics studies within a coarse-grained, structurebased model were used on two similar proteins belonging to the transcarbamylase family to probe the effects of the knot in the native structure of a protein. The first protein, N-acetylornithine transcarbamylase, contains no knot, whereas human ormithine transcarbamylase contains a trefoil knot located deep within the sequence. In addition, we also analyzed a modified transferase with the knot removed by the appropriate change of a knotmaking crossing of the protein chain. The studies of thermally and mechanically induced unfolding processes suggest a larger intrinsic stability of the protein with the knot. molecular dynamics ͉ stretching ͉ topology ͉ atomic force microscope

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Section: Methodsmentioning

confidence: 99%

Stabilizing effect of knots on proteins

Sułkowska

Sułkowski

Szymczak

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

139

147

View full text Add to dashboard Cite

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“…This would relax topological constraints while largely preserving the excluded volume (Fig.S7). The topological state of a loop was characterized by κ, the logarithm of the Alexander polynomial evaluated at −1.1 [27,[29][30][31]. To ensure equilibration, we estimated the scaling of the equilibration time with N for N ≤ 32 000, extrapolated it to large N , and ran simulations of longer chains, N = 108 000 and 256 000, to exceed the estimated equilibration time (see Supplement and Fig.…”

Section: Modelmentioning

confidence: 99%

“…Second, we used the code adjusted from [31] to calculate the value of Alexander polynomial at -1.1. The current code is at http://bitbucket.org/mirnylab/openmmpolymer in a knots folder.…”

Section: Calculation Of Alexander Polynomialmentioning

confidence: 99%

Effects of topological constraints on globular polymers

et al. 2015

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Topological constraints can affect both equilibrium and dynamic properties of polymer systems, and can play a role in the organization of chromosomes. Despite many theoretical studies, the effects of topological constraints on the equilibrium state of a single compact polymer have not been systematically studied. Here we use simulations to address this longstanding problem. We find that sufficiently long unknotted polymers differ from knotted ones in the spatial and topological states of their subchains. The unknotted globule has subchains that are mostly unknotted and form asymptotically compact RG(s) ∼ s 1/3 crumples. However, crumples display high fractal dimension of the surface d b = 2.8, forming excessive contacts and interpenetrating each other. We conclude that this topologically constrained equilibrium state resembles a conjectured crumpled globule [Grosberg et al., Journal de Physique, 1988, 49, 2095, but differs from its idealized hierarchy of self-similar, isolated and compact crumples. INTRODUCTIONTopological constraints, i.e. the inability of chains to pass through each other, have significant effects on both equilibrium and dynamic properties of polymer systems [1][2][3] and can play important roles in the organization of chromosomes [3][4][5][6]. Previous theoretical studies suggested that topological constraints per se compress polymer rings or polymer subchains by topological obstacles imposed by surrounding subchains [7][8][9]. This compression makes a subchain of length s form a spacefilling configuration that has an average radius of gyration R G (s) ∼ s 1/3 . Recent simulations of topologically constrained unconcatenated polymer rings in a melt [10][11][12][13][14] have demonstrated the effect of compression into space-filling configurations and confirmed s 1/3 scaling, thus providing strong support to previous conjectures.The role of topological constraints in the equilibrium state of a single compact and unknotted polymer remains unknown. Previous studies [3,7,8] have put forward a concept of the crumpled globule as the equilibrium state of a compact and unknotted polymer. In the crumpled globule, the subchains were suggested to be space-filling and unknotted. This conjecture remained untested for the quarter of the century. Here, we test this conjecture by comparing equilibrium compact states of a topologically constrained and unknotted polymer, referred to below as the unknotted globule, with those a topologically relaxed one, referred to below as the knotted globule (Fig. 1).Recent computational studies examined the role of topological constraints in the non-equilibrium (or quasiequilibrium) polymer states that emerge upon polymer collapse [15][16][17][18][19]. This non-equilibrium state, often referred to as the fractal globule [6,15], can indeed possess some properties of the conjectured equilibrium crumpled globule. The properties of the fractal globule, its stability [20], and its connection to the equilibrium state are yet to be understood.Elucidating the role of topological con...

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“…Such knots are particularly impressive because they are defined by the path of the polypeptide backbone alone and therefore require that a considerable segment of protein chain (at least 40 residues) has threaded through a loop. The question of how such complex topologies arise during protein folding is an intriguing one, and is of growing importance with the increasing number and complexity of knotted structures observed (10)(11)(12)(13)(14). In addition to trefoil knots, a highly intricate figure-of-eight knot (10) and a knotted structure with 5 projected crossings (15) have been observed.…”

mentioning

confidence: 99%

Exploring knotting mechanisms in protein folding

Mallam

Morris

Jackson

2008

Proc. Natl. Acad. Sci. U.S.A.

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One of the most striking topological features to be found in a protein is that of a distinct knot formed by the path of the polypeptide backbone. Such knotted structures represent some of the smallest ''self-tying'' knots observed in Nature. Proteins containing a knot deep within their structure add an extra complication to the already challenging protein-folding problem; it is not obvious how, during the process of folding, a substantial length of polypeptide chain manages to spontaneously thread itself through a loop. Here, we probe the folding mechanism of YibK, a homodimeric ␣/␤-knot protein containing a deep trefoil knot at its carboxy terminus. By analyzing the effect of mutations made in the knotted region of the protein we show that the native structure in this area remains undeveloped until very late in the folding reaction. Single-site destabilizing mutations made in the knot structure significantly affect only the folding kinetics of a lateforming intermediate and the slow dimerization step. Furthermore, we find evidence to suggest that the heterogeneity observed in the denatured state is not caused by isomerization of the single cis proline bond as previously thought, but instead could be a result of the knotting mechanism. These results allow us to propose a folding model for YibK where the threading of the polypeptide chain and the formation of native structure in the knotted region of the protein occur independently as successive events.intermediate states ͉ methyltransferases ͉ parallel pathways ͉ knotted proteins ͉ trefoil knot

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Protein knot server: detection of knots in protein structures

Cited by 95 publications

References 23 publications

Stabilizing effect of knots on proteins

Stabilizing effect of knots on proteins

Effects of topological constraints on globular polymers

Exploring knotting mechanisms in protein folding

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