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Although rare, an increasing number of proteins have been observed to contain entanglements in their native structures. To gain more insight into the significance of protein knotting, researchers have been investigating protein knot…

Biomolecules · Quantitative Biology 2022-11-08 Isabel K. Darcy , Garrett Jones , Puttipong Pongtanapaisan

We present a detailed heuristic method to quantify the degree of local energetic frustration manifested by protein molecules. Current applications are realized in computational experiments where a protein structure is visualized…

Biomolecules · Quantitative Biology 2018-12-17 A. Brenda Guzovsky , Nicholas P. Schafer , Peter G. Wolynes , Diego U. Ferreiro

The prediction of the biologically active native conformation of a protein is one of the fundamental challenges of structural biology. This problem remains yet unsolved mainly due to three factors: the partial knowledge of the effective…

Biomolecules · Quantitative Biology 2007-05-23 Jose Luis Alonso , Gregory A. Chass , Imre G. Csizmadia , Pablo Echenique , Alfonso Tarancon

Physical mechanisms underlying the empirical correlation between relative contact order (CO) and folding rate among naturally-occurring small single-domain proteins are investigated by evaluating postulated interaction schemes for a set of…

Statistical Mechanics · Physics 2007-05-23 Huseyin Kaya , Hue Sun Chan

Two proteins, one belonging to the mainly alpha class and the other belonging to the alpha/beta class, are selected to test a kinetic mechanism for protein folding. Targeted molecular dynamics is applied to generate folding pathways for…

Biological Physics · Physics 2011-01-04 Leonor Cruzeiro

In structure-based models of proteins, one often assumes that folding is accomplished when all contacts are established. This assumption may frequently lead to a conceptual problem that folding takes place in a temperature region of very…

Biomolecules · Quantitative Biology 2016-05-23 Karol Wołek , Marek Cieplak

Neither of the two prevalent theories, namely thermodynamic stability and kinetic stability, provides a comprehensive understanding of protein folding. The thermodynamic theory is misleading because it assumes that free energy is the…

Biological Physics · Physics 2013-07-22 Ji Xu , Mengzhi Han , Ying Ren , Jinghai Li

We study the folding process in the shallowly knotted protein MJ0366 within two variants of a structure-based model. We observe that the resulting topological pathways are much richer than identified in previous studies. In addition to the…

Biological Physics · Physics 2015-09-04 Mateusz Chwastyk , Marek Cieplak

Proteins are linear molecular chains that often fold to function. The topology of folding is widely believed to define its properties and function, and knot theory has been applied to study protein structure and its implications. More that…

Geometric Topology · Mathematics 2020-07-13 Colin Adams , Judah Devadoss , Mohamed Elhamdadi , Alireza Mashaghi

Novel numerical techniques, validated by an analysis of barnase and chymotrypsin inhibitor, are used to elucidate the paramount role played by the geometry of the protein backbone in steering the folding to the correct native state. It is…

Statistical Mechanics · Physics 2009-10-31 Cristian Micheletti , Jayanth R. Banavar , Amos Maritan , Flavio Seno

In spite of decades of research, much remains to be discovered about folding: the detailed structure of the initial (unfolded) state, vestigial folding instructions remaining only in the unfolded state, the interaction of the molecule with…

Biological Physics · Physics 2018-11-26 Walter A. Simmons

Kinetics of folding of a protein held in a force-clamp are compared to an unconstrained folding. The comparison is made within a simple topology-based dynamical model of ubiquitin. We demonstrate that the experimentally observed variations…

Biomolecules · Quantitative Biology 2009-11-13 Marek Cieplak , Piotr Szymczak

By observing trends in the folding kinetics of experimental 2-state proteins at their transition midpoints, and by observing trends in the barrier heights of numerous simulations of coarse grained, C-alpha model, Go proteins, we show that…

Quantitative Methods · Quantitative Biology 2009-11-10 B. Öztop , M. R. Ejtehadi , S. S. Plotkin

Using a structure-based coarse-grained model of proteins, we study the mechanism of unfolding of knotted proteins through heating. We find that the dominant mechanisms of unfolding depend on the temperature applied and are generally…

Biomolecules · Quantitative Biology 2017-01-23 Yani Zhao , Mateusz Chwastyk , Marek Cieplak

Over the years, advances in experimental and computational methods have helped us to understand the role of thermodynamic, kinetic and active (chaperone-aided) effects in coordinating the folding steps required to achieving a knotted native…

Biomolecules · Quantitative Biology 2016-10-20 Sophie E. Jackson , Antonio Suma , Cristian Micheletti

Proteins can sometimes be knotted, and for many reasons the study of knotted proteins is rapidly becoming very important. For example, it has been proposed that a knot increases the stability of a protein. Knots may also alter enzymatic…

Soft Condensed Matter · Physics 2009-07-02 Martin Lundgren , Antti J. Niemi

The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary…

Populations and Evolution · Quantitative Biology 2015-06-22 Mathieu Hemery , Olivier Rivoire

An all-atom model of proteins is used to show that the same sequence of amino acids can have many alternative structures, that are very distant from, and that can be as stable as, the corresponding native structure. Such alternative…

Biological Physics · Physics 2008-02-11 Leonor Cruzeiro

We assume that the protein folding process follows two autonomous steps: the conformational search for the native, mainly ruled by the hydrophobic effect; and, the final adjustment stage, which eventually gives stability to the native. Our…

Biological Physics · Physics 2016-07-27 J. P. Dal Molin , A. Caliri

Computer experiments are performed to investigate why protein contact networks (networks induced by spatial contacts between amino acid residues of a protein) do not have shorter average shortest path lengths in spite of their importance to…

Molecular Networks · Quantitative Biology 2011-06-02 Susan Khor