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Molecular Dynamics (MD) simulations are fundamental computational tools for the study of proteins and their free energy landscapes. However, sampling protein conformational changes through MD simulations is challenging due to the relatively…

Biomolecules · Quantitative Biology 2023-07-20 Diego E. Kleiman , Hassan Nadeem , Diwakar Shukla

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

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

Protein structure prediction is one of the most important problems in computational biology. The most successful computational approach, also called template-based modeling, identifies templates with solved crystal structures for the query…

Biomolecules · Quantitative Biology 2013-06-20 Jian Peng

We investigate the folding behavior of protein sequences by numerically studying all sequences with maximally compact lattice model through exhaustive enumeration. We get the prion-like behavior of protein folding. Individual proteins…

Biomolecules · Quantitative Biology 2014-11-18 Yong-Yun Ji , You-Quan Li , Jun-Wen Mao , Xiao-Wei Tang

Protein design has the potential to revolutionize biotechnology and medicine. While most efforts have focused on proteins with well-defined structures, increased recognition of the functional significance of intrinsically disordered…

Biomolecules · Quantitative Biology 2025-09-17 Giulio Tesei , Francesco Pesce , Kresten Lindorff-Larsen

We consider equilibrium folding transitions in lattice protein models with and without side chains. A dimensionless measure, $Omega_{c}$, is introduced to quantitatively assess the degree of cooperativity in lattice models and in real…

Soft Condensed Matter · Physics 2007-05-23 D. K. Klimov , D. Thirumalai

Due to the wide range of timescales that are present in macromolecular systems, hierarchical multiscale strategies are necessary for their computational study. Coarse-graining (CG) allows to establish a link between different system…

Protein folding is a problem of large interest since it concerns the mechanism by which the genetic information is translated into proteins with well defined three-dimensional (3D) structures and functions. Recently theoretical models have…

Biomolecules · Quantitative Biology 2007-05-23 Emidio Capriotti , Rita Casadio

Linear models, such as force constant (FC) and cluster expansions, play a key role in physics and materials science. While they can in principle be parametrized using regression and feature selection approaches, the convergence behavior of…

Materials Science · Physics 2021-01-14 Erik Fransson , Fredrik Eriksson , Paul Erhart

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

We adopt the point of view that analysis of the stability of the protein folding process is central to understanding the underlying physics of folding. Stability of the folding process means that many perturbations do not disrupt the…

Biological Physics · Physics 2011-12-30 Walter Simmons , Joel L. Weiner

Machine-learning models that learn from data to predict how protein sequence encodes function are emerging as a useful protein engineering tool. However, when using these models to suggest new protein designs, one must deal with the vast…

Quantitative Methods · Quantitative Biology 2021-07-07 Brian L. Hie , Kevin K. Yang

We propose a data-driven, coarse-graining formulation in the context of equilibrium statistical mechanics. In contrast to existing techniques which are based on a fine-to-coarse map, we adopt the opposite strategy by prescribing a…

Machine Learning · Statistics 2017-02-01 Markus Schöberl , Nicholas Zabaras , Phaedon-Stelios Koutsourelakis

Through evolution, nature has presented a set of remarkable protein materials, including elastins, silks, keratins and collagens with superior mechanical performances that play crucial roles in mechanobiology. However, going beyond natural…

Materials Science · Physics 2023-12-19 Bo Ni , David L. Kaplan , Markus J. Buehler

This paper presents a novel Differential Evolution algorithm for protein folding optimization that is applied to a three-dimensional AB off-lattice model. The proposed algorithm includes two new mechanisms. A local search is used to improve…

Artificial Intelligence · Computer Science 2018-05-08 Borko Bošković , Janez Brest

The stability of model proteins with designed sequences is assessed in terms of the number of sequences (obtained from the designed sequence through mutations), which fold into 5the ``native'' conformation. By a complete enumeration of the…

Soft Condensed Matter · Physics 2009-10-31 R. A Broglia , G. Tiana , H. E. Roman , E. Vigezzi , E. I. Shakhnovich

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

Protein design is the inverse approach of the three-dimensional (3D) structure prediction for elucidating the relationship between the 3D structures and amino acid sequences. In general, the computation of the protein design involves a…

Biological Physics · Physics 2021-07-14 Tomoei Takahashi , George Chikenji , Kei Tokita

In this study, the distributions of protein structure classes (or folding types) of experimentally determined structures from a legacy dataset and a comprehensive database (SCOP) are modeled precisely with geometric constructs such as…

Biomolecules · Quantitative Biology 2025-10-21 Boryeu Mao