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We review theoretical approaches, experiments and numerical simulations that have been recently proposed to investigate the folding problem in single-domain proteins. From a theoretical point of view, we emphasize the energy landscape…

Biological Physics · Physics 2008-10-20 Ivan Junier , Felix Ritort

The distances over which biological molecules and their complexes can function range from a few nanometres, in the case of folded structures, to millimetres, for example during chromosome organization. Describing phenomena that cover such…

Soft Condensed Matter · Physics 2011-09-28 Changbong Hyeon , D. Thirumalai

Theory of multi-dimensional representation of free energy surface of protein folding is developed by adopting structural order parameters of multiple regions in protein as multiple coordinates. Various scenarios of folding are classified in…

Biomolecules · Quantitative Biology 2009-11-13 Kazuhito Itoh , Masaki Sasai

Molecular structure generation is a fundamental problem that involves determining the 3D positions of molecules' constituents. It has crucial biological applications, such as molecular docking, protein folding, and molecular design. Recent…

Machine Learning · Computer Science 2025-08-27 Wenyin Zhou , Christopher Iliffe Sprague , Vsevolod Viliuga , Matteo Tadiello , Arne Elofsson , Hossein Azizpour

Predicting the structure of a protein from its sequence is a cornerstone task of molecular biology. Established methods in the field, such as homology modeling and fragment assembly, appeared to have reached their limit. However, this year…

Machine Learning · Computer Science 2018-12-05 Georgy Derevyanko , Guillaume Lamoureux

The intricate three-dimensional geometries of protein tertiary structures underlie protein function and emerge through a folding process from one-dimensional chains of amino acids. The exact spatial sequence and configuration of amino…

Biomolecules · Quantitative Biology 2021-02-24 Nora Molkenthin , Steffen Mühle , Antonia S J S Mey , Marc Timme

Energy landscapes play a crucial role in shaping dynamics of many real-world complex systems. System evolution is often modeled as particles moving on a landscape under the combined effect of energy-driven drift and noise-induced diffusion,…

Computational Engineering, Finance, and Science · Computer Science 2025-03-04 Ruikun Li , Huandong Wang , Qingmin Liao , Yong Li

The local structure of a protein strongly impacts its function and interactions with other molecules. Therefore, a concise, informative representation of a local protein environment is essential for modeling and designing proteins and…

Protein folding is one of the age-old biological problems that refers to the mechanism of understanding and predicting how a protein's linear sequence of amino acids folds into its specific three dimensional structure.This structure is…

Advances in deep learning have opened an era of abundant and accurate predicted protein structures; however, similar progress in protein ensembles has remained elusive. This review highlights several recent research directions towards…

Biomolecules · Quantitative Biology 2025-09-23 Bowen Jing , Bonnie Berger , Tommi Jaakkola

Predicting the structure of multi-protein complexes is a grand challenge in biochemistry, with major implications for basic science and drug discovery. Computational structure prediction methods generally leverage pre-defined structural…

Biomolecules · Quantitative Biology 2021-01-26 Stephan Eismann , Raphael J. L. Townshend , Nathaniel Thomas , Milind Jagota , Bowen Jing , Ron O. Dror

Exploring and understanding the protein-folding problem has been a long-standing challenge in molecular biology. Here, using molecular dynamics simulation, we reveal how parallel distributed adjacent planar peptide groups of unfolded…

Biomolecules · Quantitative Biology 2019-01-11 Xiaoliang Ma , Chengyu Hou , Liping Shi , Long Li , Jiacheng Li , Lin Ye , Lin Yang , Xiaodong He

The protein folding problem is stated and a list of properties that do not depend upon specific molecules is compiled and analyzed. The relationship of this analysis to future simulations is emphasized. The choice of power and time as…

Biological Physics · Physics 2017-09-26 Walter A. Simmons

We present a differentiable formalism for learning free energies that is capable of capturing arbitrarily complex model dependencies on coarse-grained coordinates and finite-temperature response to variation of general system parameters.…

Computational Physics · Physics 2024-05-31 Blake R. Duschatko , Xiang Fu , Cameron Owen , Yu Xie , Albert Musaelian , Tommi Jaakkola , Boris Kozinsky

Coarse-graining is a powerful tool for extending the reach of dynamic models of proteins and other biological macromolecules. Topological coarse-graining, in which biomolecules or sets thereof are represented via graph structures, is a…

Biomolecules · Quantitative Biology 2021-09-15 Vy Duong , Elizabeth Diessner , Gianmarc Grazioli , Rachel W. Martin , Carter T. Butts

Characterization of protein energy landscape and conformational ensembles is important for understanding mechanisms of protein folding and function. We studied ensembles of bound and unbound conformations of six proteins to explore their…

Biological Physics · Physics 2012-11-06 Anatoly M. Ruvinsky , Tatsiana Kirys , Alexander V. Tuzikov , Ilya A. Vakser

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

Accurately assigning folds for divergent protein sequences is a major obstacle to structural studies and underlies the inverse protein folding problem. Herein, we outline our theories for fold-recognition in the "twilight-zone" of sequence…

Quantitative Methods · Quantitative Biology 2010-08-31 Yoojin Hong , Kyung Dae Ko , Gaurav Bhardwaj , Zhenhai Zhang , Damian B. van Rossum , Randen L. Patterson

Significant progress in computer hardware and software have enabled molecular dynamics (MD) simulations to model complex biological phenomena such as protein folding. However, enabling MD simulations to access biologically relevant…

Biomolecules · Quantitative Biology 2019-08-02 Heng Ma , Debsindhu Bhowmik , Hyungro Lee , Matteo Turilli , Michael T. Young , Shantenu Jha , Arvind Ramanathan

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
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