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Proteins must fold quickly to acquire their biologically functional three-dimensional native structures. Hence, these are mainly stabilized by local contacts, while intricate topologies such as knots are rare. Here, we reveal the existence…

Biomolecules · Quantitative Biology 2019-06-20 Marco Baiesi , Enzo Orlandini , Flavio Seno , Antonio Trovato

Natural protein molecules are exceptional polymers. Encoded in apparently random strings of amino-acids, these objects perform clear physical tasks that are rare to find by simple chance. Accurate folding, specific binding, powerful…

Biomolecules · Quantitative Biology 2017-10-09 Diego U. Ferreiro , Elizabeth A. Komives , Peter G. Wolynes

Knotted proteins embed a physical (i.e., open) knot within their native structures. For decades, significant effort has been devoted to elucidating the functional role of knots in proteins, yet no consensus has been reached. Here, using…

Biomolecules · Quantitative Biology 2026-03-13 João NC Especial , Patrícia FN Faísca

We solve a model that takes into account entropic barriers, frustration, and the organization of a protein-like molecule. For a chain of size $M$, there is an effective folding transition to an ordered structure. Without frustration, this…

Condensed Matter · Physics 2009-10-28 Carlos J. Camacho

We use a free energy functional theory to elucidate general properties of heterogeneously ordering, fast folding proteins, and we test our conclusions with lattice simulations. We find that both structural and energetic heterogeneity can…

Disordered Systems and Neural Networks · Physics 2009-10-31 Steven S. Plotkin , Jose N. Onuchic

Binding interactions between proteins and other molecules mediate numerous cellular processes, including metabolism, signaling, and regulation of gene expression. These interactions evolve in response to changes in the protein's chemical or…

Populations and Evolution · Quantitative Biology 2015-02-19 Michael Manhart , Alexandre V. Morozov

Molecules provide the ultimate language in terms of which physiology and pathology must be understood. Myriads of proteins participate in elaborate networks of interactions and perform chemical activities coordinating the life of cells. To…

Biomolecules · Quantitative Biology 2025-02-10 R. Gonzalo Parra , Elizabeth A. Komives , Peter G. Wolynes , Diego U. Ferreiro

The folding of a protein towards its native state is a rather complicated process. However there are empirical evidences that the folding time correlates with the contact order, a simple measure of the spatial organisation of the native…

Soft Condensed Matter · Physics 2017-12-06 Marco Baiesi , Enzo Orlandini , Flavio Seno , Antonio Trovato

Protein sequences serve as a natural record of the evolutionary constraints that shape their functional structures. We show that it is possible to use only sequence information to go beyond predicting native structures and global stability…

Biomolecules · Quantitative Biology 2025-07-02 Ezequiel A. Galpern , Ernesto A. Roman , Diego U. Ferreiro

A general theoretical framework is developed using free energy functional methods to understand the effects of heterogeneity in the folding of a well-designed protein. Native energetic heterogeneity arising from non-uniformity in native…

Disordered Systems and Neural Networks · Physics 2007-05-23 Steven S. Plotkin , Jose N. Onuchic

Cotranslational folding depends on the folding speed and stability of the nascent protein. It remains difficult, however, to predict which proteins cotranslationally fold. Here, we simulate evolution of model proteins to investigate how…

Biomolecules · Quantitative Biology 2020-10-28 Victor Zhao , William M. Jacobs , Eugene I. Shakhnovich

Nonnative residual interactions have attracted increasing attention in recent protein folding researches. Experimental and theoretical investigations had been set out to catch nonnative contacts that might dominate key events in protein…

Biological Physics · Physics 2017-01-30 Yunxiang Sun , Dengming Ming

The energy landscapes of proteins have evolved to be different from most random heteropolymers. Many studies have concluded that evolutionary selection for rapid and reliable folding to a given structure that is stable at biological…

Disordered Systems and Neural Networks · Physics 2009-11-10 Steven S. Plotkin , Peter G. Wolynes

The principles underlying protein folding remains one of Nature's puzzles with important practical consequences for Life. An approach that has gathered momentum since the late 1990's, looks at protein hetero-polymers and their folding…

Computational Engineering, Finance, and Science · Computer Science 2011-10-05 Susan Khor

Proteins with nontrivial topology, containing knots and slipknots, have the ability to fold to their native states without any additional external forces invoked. A mechanism is suggested for folding of these proteins, such as YibK and…

Biomolecules · Quantitative Biology 2010-01-06 Joanna I. Sułkowska , Piotr Sułkowski , José N. Onuchic

Natural protein sequences that self-assemble to form globular structures are compact with high packing densities in the folded states. It is known that proteins unfold upon addition of denaturants, adopting random coil structures. The…

Biomolecules · Quantitative Biology 2016-12-02 Himadri S. Samanta , Pavel I. Zhuravlev , Michael Hinczewski , Naoto Hori , Shaon Chakrabarti , D. Thirumalai

One of the most puzzling and unsolved challenges in molecular biology is understanding how proteins fold. Despite having advanced predictive tools that can accurately estimate the native structures of proteins, we still lack a comprehensive…

Biomolecules · Quantitative Biology 2026-01-13 Jorge Vila

Understanding the biological function of knots in proteins and their folding process is an open and challenging question in biology. Recent studies classify the topology and geometry of knotted proteins by analysing the distribution of a…

How proteins fold remains a central unsolved problem in biology. While the idea of a folding code embedded in the amino acid sequence was introduced more than 6 decades ago, this code remains undefined. While we now have powerful predictive…

Biomolecules · Quantitative Biology 2025-11-04 Carlos Bustamante , Christian Kaiser , Erik Lindahl , Robert Sosa , Giovanni Volpe

The protein folding problem must ultimately be solved on all length scales from the atomic up through a hierarchy of complicated structures. By analyzing the stability of the folding process using physics and mathematics, this paper shows…

Biological Physics · Physics 2015-05-28 Walter Simmons , Joel L. Weiner
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