Molecular knots in biology and chemistry

Knots and entanglements are ubiquitous. Beyond their aesthetic appeal, these fascinating topological entities can be either useful or cumbersome. In recent decades, the importance and prevalence of molecular knots have been increasingly recognised by scientists from different disciplines. In this review, we provide an overview on the various molecular knots found in naturally occurring biological systems (DNA, RNA and proteins), and those created by synthetic chemists. We discuss the current knowledge in these fields, including recent developments in experimental and, in some cases, computational studies which are beginning to shed light into the complex interplay between the structure, formation and properties of these topologically intricate molecules.

• Publication year

  2015

• Venue

  Journal of Physics: Condensed Matter

• Publication date

  2015-08-20

• Fields of study

  Biology, Medicine, Physics, Chemistry

• Identifiers
  DOI 10.1088/0953-8984/27/35/354101PMID 26291690
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• A structure for deoxyribose nucleic acid

  2017cited by this paper
• Absence of knots in known RNA structures

  2015influential reference
• Mechanistic insights into the folding of knotted proteins in vitro and in vivo.

  2015cited by this paper
• Sequence determines degree of knottedness in a coarse-grained protein model.

  2015cited by this paper
• Mechanically tightening a protein slipknot into a trefoil knot.

  2014cited by this paper
• KnotProt: a database of proteins with knots and slipknots

  2014cited by this paper
• A fast and robust iterative algorithm for prediction of RNA pseudoknotted secondary structures

  2014cited by this paper
• Structural biology of glycoprotein hormones and their receptors: insights to signaling.

  2014cited by this paper
• Pierced Lasso Bundles Are a New Class of Knot-like Motifs

  2014cited by this paper
• A Star of David catenane.

  2014cited by this paper
• Self-assembly of a giant molecular Solomon link from 30 subcomponents.

  2014cited by this paper
• Backbone NMR assignments of a topologically knotted protein in urea-denatured state

  2014cited by this paper
• Backbone NMR assignments of a topologically knotted protein in urea-denatured state

  2014cited by this paper
• New mini- zincin structures provide a minimal scaffold for members of this metallopeptidase superfamily

  2014cited by this paper
• Chemistry and biology of cyclotides: circular plant peptides outside the box.

  2014cited by this paper
• Electrophoretic mobility of supercoiled, catenated and knotted DNA molecules

  2014cited by this paper
• Homochiral and meso figure eight knots and a Solomon link.

  2014influential reference
• Effects of knot type in the folding of topologically complex lattice proteins.

  2014influential reference
• Lanthanide template synthesis of a molecular trefoil knot.

  2014cited by this paper
• The benefit of DNA supercoiling during replication.

  2013cited by this paper
• Tight knots in proteins: can they block the mitochondrial pores?

  2013cited by this paper
• Template synthesis of molecular knots.

  2013cited by this paper
• Effects of Knots on Protein Folding Properties

  2013influential reference
• Computational prediction of RNA secondary structure.

  2013cited by this paper
• Hysteresis as a Marker for Complex, Overlapping Landscapes in Proteins.

  2013cited by this paper
• The Role of Non-Native Interactions in the Folding of Knotted Proteins: Insights from Molecular Dynamics Simulations

  2013cited by this paper
• Pfam: the protein families database

  2013cited by this paper
• Tightening and Untying the Knot in Human Carbonic Anhydrase III.

  2013cited by this paper
• Influence of chain stiffness on knottedness in single polymers.

  2013cited by this paper
• Single-molecule detection reveals knot sliding in TrmD denaturation.

  2013cited by this paper
• Simultaneous self-assembly of a [2]catenane, a trefoil knot, and a Solomon link from a simple pair of ligands.

  2013cited by this paper
• Tetrameric Cyclic Double Helicates as a Scaffold for a Molecular Solomon Link

  2013cited by this paper
• Knotting pathways in proteins.

  2013cited by this paper
• Interplay between native topology and non-native interactions in the folding of tethered proteins

  2013cited by this paper
• Knot localization in proteins.

  2013cited by this paper
• Topological friction strongly affects viral DNA ejection

  2013cited by this paper
• Hepatitis C virus RNA translation.

  2013cited by this paper
• Non-specific binding of Na+ and Mg2+ to RNA determined by force spectroscopy methods

  2012cited by this paper
• Knot theory in understanding proteins

  2012cited by this paper
• RNA Structure: Pseudoknots

  2012cited by this paper
• pKNOT v.2: the protein KNOT web server

  2012cited by this paper
• McGenus: a Monte Carlo algorithm to predict RNA secondary structures with pseudoknots

  2012cited by this paper
• Metal template synthesis of molecular knots and links.

  2012cited by this paper
• Conservation of complex knotting and slipknotting patterns in proteins

  2012cited by this paper
• Mechanically untying a protein slipknot: multiple pathways revealed by force spectroscopy and steered molecular dynamics simulations.

  2012cited by this paper
• How Difficult Is It to Fold a Knotted Protein? In Silico Insights from Surface-Tethered Folding Experiments

  2012cited by this paper
• Characterising the Folding Pathways of Topologically Knotted Proteins

  2012cited by this paper
• The Role of Non-Native Interactions in the Folding of Knotted Proteins

  2012cited by this paper
• Discovery of an Organic Trefoil Knot

  2012cited by this paper
• Knot formation in newly translated proteins is spontaneous and accelerated by chaperonins.

  2012cited by this paper
• Structures and folding pathways of topologically knotted proteins

  2011influential reference
• IPknot: fast and accurate prediction of RNA secondary structures with pseudoknots using integer programming

  2011cited by this paper
• Faculty Opinions recommendation of Crystal structure of the HCV IRES central domain reveals strategy for start-codon positioning.

  2011cited by this paper
• The effect of Parkinson's-disease-associated mutations on the deubiquitinating enzyme UCH-L1.

  2011cited by this paper
• Dynamic combinatorial donor-acceptor catenanes in water: access to unconventional and unexpected structures.

  2011cited by this paper
• Strategies and tactics for the metal-directed synthesis of rotaxanes, knots, catenanes, and higher order links.

  2011cited by this paper
• Telomerase: an RNP enzyme synthesizes DNA.

  2011cited by this paper
• Crystal structure of the HCV IRES central domain reveals strategy for start-codon positioning.

  2011cited by this paper
• Synthesis of a D3-symmetric "trefoil" knotted cyclophane.

  2011cited by this paper
• Active-metal template synthesis of a molecular trefoil knot.

  2011cited by this paper
• Protein stabilization in a highly knotted protein polymer.

  2011cited by this paper
• Chemical topology: complex molecular knots, links, and entanglements.

  2011influential reference
• A synthetic molecular pentafoil knot.

  2011cited by this paper
• Topo IV is the topoisomerase that knots and unknots sister duplexes during DNA replication

  2011cited by this paper
• Tying the knot: The cystine signature and molecular-recognition processes of the vascular endothelial growth factor family of angiogenic cytokines

  2011cited by this paper
• Biophysics of knotting.

  2010cited by this paper
• Slipknotting upon native-like loop formation in a trefoil knot protein

  2010influential reference
• Structure and folding of a designed knotted protein

  2010cited by this paper
• Untying knots in proteins.

  2010cited by this paper
• Untying Knots in Proteins

  2010influential reference
• Knotted vs. Unknotted Proteins: Evidence of Knot-Promoting Loops

  2010cited by this paper
• The folding of knotted proteins: insights from lattice simulations

  2010cited by this paper
• Synthesis of a molecular trefoil knot by folding and closing on an octahedral coordination template.

  2010cited by this paper
• TT2NE: a novel algorithm to predict RNA secondary structures with pseudoknots

  2010influential reference
• ProbKnot: fast prediction of RNA secondary structure including pseudoknots.

  2010cited by this paper
• Experimental detection of knotted conformations in denatured proteins

  2010cited by this paper
• Predicting Atomic Details of the Unfolding Pathway for YibK, a Knotted Protein from the SPOUT Superfamily

  2010influential reference
• The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

  2010influential reference
• The HCV IRES pseudoknot positions the initiation codon on the 40S ribosomal subunit.

  2010cited by this paper
• Small self-cleaving ribozymes.

  2010cited by this paper
• A Stevedore's Protein Knot

  2010cited by this paper
• Improved free energy parameters for RNA pseudoknotted secondary structure prediction.

  2010cited by this paper
• Predicting knot and catenane type of products of site-specific recombination on twist knot substrates.

  2010cited by this paper
• Jamming proteins with slipknots and their free energy landscape.

  2009cited by this paper
• Untangling the folding mechanism of the 52‐knotted protein UCH‐L3

  2009influential reference
• Dodging the crisis of folding proteins with knots

  2009influential reference
• Active metal template synthesis of rotaxanes, catenanes and molecular shuttles.

  2009cited by this paper
• Encyclopedia of life sciences

  2009cited by this paper
• Structure and function of HCV IRES domains

  2009cited by this paper
• DNA supercoiling and its role in DNA decatenation and unknotting

  2009cited by this paper
• Dynamic combinatorial synthesis of a catenane based on donor–acceptor interactions in water

  2009cited by this paper
• How does a knotted protein fold?

  2009cited by this paper
• Conformational changes in a plant ketol-acid reductoisomerase upon Mg(2+) and NADPH binding as revealed by two crystal structures.

  2009cited by this paper
• FlexStem: improving predictions of RNA secondary structures with pseudoknots by reducing the search space

  2008cited by this paper
• Solution structure of the U2 snRNP protein Rds3p reveals a knotted zinc-finger motif

  2008cited by this paper
• Knotted fusion proteins reveal unexpected possibilities in protein folding.

  2008influential reference
• Stabilizing effect of knots on proteins

  2008cited by this paper
• Simulations of knotting in confined circular DNA.

  2008cited by this paper
• Frameshifting RNA pseudoknots: Structure and mechanism

  2008cited by this paper
• CHIRALITY VS. HOMFLY AND KAUFFMAN POLYNOMIALS

  2008cited by this paper

• Detecting the body's reproductive hormonal brake against tissue overgrowth: Micrin/SgII-70.

  2026cites this paper
• Interplay of coil-globule transitions and aggregation in homopolymer aqueous solutions: Simulation and topological insights.

  2025cites this paper
• Topological architectures enriched by cooperative acetylene coordination

  2025cites this paper
• Highly selective synthesis and near-infrared photothermal response of heterometallic double trefoil knot and D-type [2]catenanes

  2025cites this paper
• Remote control of synthetic knots through peptide sequences

  2025cites this paper
• Lasso Peptide Syanodin I: Loop-Pulling Two-Step Thermal Unthreading Mechanism.

  2025cites this paper
• Ribbonlength upper bounds for small crossing knots and links

  2025cites this paper
• Cyclodextrin-based rotaxanes as a versatile platform for biological and medicinal applications

  2025cites this paper
• Bounded ribbonlength for knot families and multi-twist M\"obius bands

  2025cites this paper
• Folding a Molecular Strand into a Trefoil Knot of Single Handedness with Co(II)/Co(III) Chaperones

  2024cites this paper
• Exploring the electronic structure of knotted proteins: the case of two ornithine transcarbamylase family

  2024cites this paper
• Evolutionary Khovanov homology

  2024cites this paper
• Activity-driven polymer knotting for macromolecular topology engineering

  2024cites this paper
• Molecular entanglement can strongly increase basicity

  2024cites this paper
• Tying a true topological protein knot by cyclization.

  2024cites this paper
• Mechanical scission of a knotted polymer

  2024influential citation
• Fine-Tuning of the Sequential Self-Assembly of Entangled Polyhedra by Exploiting the Side-Chain Effect.

  2024cites this paper
• Pulling Forces Differentially Affect Refolding Pathways Due to Entangled Misfolded States in SARS-CoV-1 and SARS-CoV-2 Receptor Binding Domain

  2024cites this paper
• Quantum-chemical study of atomic X 30 trefoil knots with X = {H, He, Li, Be, B, C}*

  2024cites this paper
• A Simple and Efficient Algorithm to Identify the Chirality of Polymer Knots Based on the Alexander Polynomial

  2024cites this paper
• Linear upper bounds on ribbonlength of knots and links

  2024cites this paper
• Conformational and Structural Characterization of Knotted Proteins.

  2024cites this paper
• Integrating Graph Convolutional Network to BiLSTM for Enhanced Polymer Knot Identification

  2024cites this paper
• Cinquefoil Knot Possessing Dynamic and Tunable Metal Coordination.

  2024cites this paper
• Theoretical investigation of the lack of chiral self-sorting behaviour of a molecular cinquefoil knot

  2023cites this paper
• Structure, dynamics, and stability of the smallest and most complex 71 protein knot

  2023cites this paper
• Iminopyrrole-Based Self-Assembly: A Route to Intrinsically Flexible Molecular Links and Knots.

  2023cites this paper
• Self-Assembly of an [M8L24]16+ Intertwined Cube and a Giant [M12L16]24+ Orthobicupola.

  2023cites this paper
• AlphaFold Blindness to Topological Barriers Affects Its Ability to Correctly Predict Proteins’ Topology

  2023cites this paper
• Knot Formation on DNA Pushed Inside Chiral Nanochannels

  2023cites this paper
• Resolution of Expanded Porphyrinoids: A Path to Persistent Chirality and Appealing Chiroptical Properties.

  2023cites this paper
• Folding and functions of knotted proteins.

  2023cites this paper
• The mechanical bond in biological systems

  2023cites this paper
• Acoustic radiation forces and torques on elastic micro rings in standing waves

  2023cites this paper
• Mechanical tightening of a synthetic molecular knot

  2023cites this paper
• Secure communication using low dimensional topological elements

  2022cites this paper
• Cell-Free Expression to Probe Co-Translational Insertion of an Alpha Helical Membrane Protein

  2022cites this paper
• High yielding stimuli-responsive contra-helical trefoil knots

  2022cites this paper
• Di-2,7-pyrenidecaphyrin(1.1.0.0.0.1.1.0.0.0) and Its Bis-Organopalladium Complexes: Synthesis and Chiroptical Properties.

  2022cites this paper
• Elucidation of folding pathways of knotted proteins.

  2022cites this paper
• Social Self-Sorting Synthesis of Molecular Knots

  2022cites this paper
• Knotting matters: orderly molecular entanglements

  2022cites this paper
• Computational Design of Extraordinarily Stable Peptide Structures through Side-Chain-Locked Knots.

  2022cites this paper
• Folded ribbonlength of 2-bridge knots

  2022cites this paper
• Methods to study folding of alpha-helical membrane proteins in lipids

  2022cites this paper
• AlphaFold predicts the most complex protein knot and composite protein knots

  2022cites this paper
• A trefoil knot self-templated through imination in water

  2022cites this paper
• The dynamic, motile and deformative properties of RNA nanoparticles facilitate the third milestone of drug development.

  2022cites this paper
• How Cooperatively Folding Are Homopolymer Molecular Knots?

  2022cites this paper
• Investigation of the structural dynamics of a knotted protein and its unknotted analog using molecular dynamics

  2022cites this paper
• Vernier template synthesis of molecular knots

  2022cites this paper
• Self-Assembly of Molecular Trefoil Knots Featuring Pentadecanuclear Homoleptic AuI-, AuI/AgI-, or AuI/CuI-Alkynyl Coordination.

  2022cites this paper
• Quantifying the effects of slit confinement on polymer knots using the tube model.

  2022cites this paper
• Spontaneous knotting of a flexible fiber in chaotic flows.

  2021cites this paper
• Non‐Covalent Interaction‐Directed Coordination‐Driven Self‐Assembly of Non‐Trivial Supramolecular Topologies

  2021cites this paper
• Channels with Helical Modulation Display Stereospecific Sensitivity for Chiral Superstructures

  2021cites this paper
• Entanglements of structure elements revealed in RNA 3D models

  2021cites this paper
• Circuit Topology for Bottom-Up Engineering of Molecular Knots

  2021cites this paper
• Tying up the Loose Ends: A Mathematically Knotted Protein

  2021cites this paper
• Macromolecular Topology Engineering

  2021cites this paper
• Time-dependent knotting of agitated chains.

  2021cites this paper
• Converging experimental and computational views of the knotting mechanism of a small knotted protein.

  2021cites this paper
• Untangling knotty problems

  2021cites this paper
• Self-Assembly of Molecular Figure-Eight Knots Induced by Quadruple Stacking Interactions.

  2020cites this paper
• Macrocyclic multinuclear metal complexes acting as catalysts for organic synthesis

  2020cites this paper
• Contextual Emergence of Physical Properties

  2020cites this paper
• Developing the tube theory for polymer knots

  2020cites this paper
• Knotting a molecular strand can invert macroscopic effects of chirality

  2020cites this paper
• Tying different knots in a molecular strand

  2020cites this paper
• Isogonal weavings on the sphere: knots, links, polycatenanes.

  2020cites this paper
• Transmembrane Ion Channels Formed by a Star of David [2]Catenane and a Molecular Pentafoil Knot

  2020cites this paper
• Comparison of Fused Deposition Modeling and Color Jet 3D Printing Technologies for the Printing of Mathematical Geometries

  2020cites this paper
• Using Parametric Mathematical Modeling to Develop a Geometric and Topological Intuition for Molecular Knots

  2020influential citation
• Open questions in functional molecular topology

  2020cites this paper
• A molecular endless (74) knot

  2020cites this paper
• Protein corona, understanding the nanoparticle-protein interactions and future perspectives: A critical review.

  2020cites this paper
• Effects of turn-structure on folding and entanglement in artificial molecular overhand knots

  2020cites this paper
• Contextual Emergence of Physical Properties

  2020cites this paper
• Total normalcy of knots

  2019cites this paper
• Synchronized On/Off Switching of Four Binding Sites for Water in a Molecular Solomon Link.

  2019cites this paper
• Topological descriptions of protein folding

  2019cites this paper
• Protein knots provide mechano-resilience to an AAA+ protease-mediated proteolysis with profound ATP energy expenses.

  2019cites this paper
• Accelerated sampling methods for high dimensional molecular systems

  2019cites this paper
• Proteins' Knotty Problems.

  2019cites this paper
• Effects of knot tightness at the molecular level

  2019cites this paper
• Coordination Chemistry of a Molecular Pentafoil Knot

  2019cites this paper
• Metal–Organic Self-Assembled Trefoil Knots for C—Br Bond Activation

  2019cites this paper
• Carbon nanotube knots

  2019cites this paper
• Computational methods in the study of self-entangled proteins: a critical appraisal

  2019cites this paper
• Knotted proteins: Tie etiquette in structural biology

  2019cites this paper
• Untying a Knotted SPOUT RNA Methyltransferase by Circular Permutation Results in a Domain-Swapped Dimer.

  2019cites this paper
• Circular exonic RNAs: When RNA structure meets topology.

  2019cites this paper
• Coordination-Driven Self-Assembly of a Molecular Knot Comprising Sixteen Crossings.

  2018cites this paper
• Molecular Trefoil Knot from a Trimeric Circular Helicate.

  2018cites this paper
• Stable elastic knots with no self-contact

  2018cites this paper
• Knotting statistics for polygons in lattice tubes

  2018cites this paper
• Evaluating the Jones polynomial with tensor networks.

  2018cites this paper
• Coarse-grained models of double-stranded DNA based on experimentally determined knotting probabilities

  2018cites this paper
• Searching the Optimal Folding Routes of a Complex Lasso Protein

  2018cites this paper
• Knots, Music and DNA.

  2018cites this paper