Subscribe to the gold package and get unlimited access to Shamra Academy
Register a new userTightening of knots in proteins
150
0
0.0
(
0
)
Ask ChatGPT about the research
No Arabic abstract
We perform theoretical studies of stretching of 20 proteins with knots within a coarse grained model. The knots ends are found to jump to well defined sequential locations that are associated with sharp turns whereas in homopolymers they diffuse around and eventually slide off. The waiting times of the jumps are increasingly stochastic as the temperature is raised. Larger knots do not return to their native locations when a protein is released after stretching.
rate research
Read More
Molecular dynamics studies within a coarse-grained structure based model were used on two similar proteins belonging to the transcarbamylase family to probe the effects in the native structure of a knot. 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 knot-making 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.
Protein molecules can be approximated by discrete polygonal chains of amino acids. Standard topological tools can be applied to the smoothening of the polygons to introduce a topological classification of proteins, for example, using the self-linking number of the corresponding framed curves. In this paper we add new details to the standard classification. Known definitions of the self-linking number apply to non-singular framings: for example, the Frenet framing cannot be used if the curve has inflection points. Meanwhile in the discrete proteins the special points are naturally resolved. Consequently, a separate integer topological characteristics can be introduced, which takes into account the intrinsic features of the special points. For large number of proteins we compute integer topological indices associated with the singularities of the Frenet framing. We show how a version of the Calugareanus theorem is satisfied for the associated self-linking number of a discrete curve. Since the singularities of the Frenet framing correspond to the structural motifs of proteins, we propose topological indices as a technical tool for the description of the folding dynamics of proteins.
The ongoing effort to detect and characterize physical entanglement in biopolymers has so far established that knots are present in many globular proteins and also abound in viral DNA packaged inside bacteriophages. RNA molecules, on the other hand, have not yet been systematically screened for the occurrence of physical knots. We have accordingly undertaken the systematic profiling of the ~6,000 RNA structures present in the protein data bank. The search identified no more than three deeply-knotted RNA molecules. These are ribosomal RNAs solved by cryo-em and consist of about 3,000 nucleotides. Compared to the case of proteins and viral DNA, the observed incidence of RNA knots is therefore practically negligible. This suggests that either evolutionary selection, or thermodynamic and kinetic folding mechanisms act towards minimizing the entanglement of RNA to an extent that is unparalleled by other types of biomolecules. The properties of the three observed RNA knotting patterns provide valuable clues for designing RNA sequences capable of self-tying in a twist-knot fold.
Experiments indicate that unbinding rates of proteins from DNA can depend on the concentration of proteins in nearby solution. Here we present a theory of multi-step replacement of DNA-bound proteins by solution-phase proteins. For four different kinetic scenarios we calculate the depen- dence of protein unbinding and replacement rates on solution protein concentration. We find (1) strong effects of progressive rezipping of the solution-phase protein onto DNA sites liberated by unzipping of the originally bound protein; (2) that a model in which solution-phase proteins bind non-specifically to DNA can describe experiments on exchanges between the non specific DNA- binding proteins Fis-Fis and Fis-HU; (3) that a binding specific model describes experiments on the exchange of CueR proteins on specific binding sites.
Intrinsically disordered proteins (IDPs) do not possess well-defined three-dimensional structures in solution under physiological conditions. We develop all-atom, united-atom, and coarse-grained Langevin dynamics simulations for the IDP alpha-synuclein that include geometric, attractive hydrophobic, and screened electrostatic interactions and are calibrated to the inter-residue separations measured in recent smFRET experiments. We find that alpha-synuclein is disordered with conformational statistics that are intermediate between random walk and collapsed globule behavior. An advantage of calibrated molecular simulations over constraint methods is that physical forces act on all residues, not only on residue pairs that are monitored experimentally, and these simulations can be used to study oligomerization and aggregation of multiple alpha-synuclein proteins that may precede amyloid formation.
Log in to be able to interact and post comments
comments
Fetching comments
Sign in to be able to follow your search criteria
