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This paper deepens into the analysis of the protein secondary structure using Frenet frame to describe the curvature and torsion of the discrete curve formed by the protein $\alpha$-carbons. We show how a simple criterion based on the…

Biological Physics · Physics 2025-12-08 M. Prados , M. D. Hernández de la Torre , F. de Soto

Most widely used ligand docking methods assume a rigid protein structure. This leads to problems when the structure of the target protein deforms upon ligand binding. In particular, the ligand's true binding pose is often scored very…

Biomolecules · Quantitative Biology 2023-03-22 Patricia Suriana , Joseph M. Paggi , Ron O. Dror

Computational docking methods can provide structural models of protein-protein complexes, but protein backbone flexibility upon association often thwarts accurate predictions. In recent blind challenges, medium or high accuracy models were…

Biomolecules · Quantitative Biology 2020-12-29 Ameya Harmalkar , Jeffrey J. Gray

Reliable evaluation of protein structure predictions remains challenging, as metrics like pLDDT capture energetic stability but often miss subtle errors such as atomic clashes or conformational traps reflecting topological frustration…

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

Two-state cooperativity is an important characteristic in protein folding. It is defined by a depletion of states lying energetically between folded and unfolded conformations. While there are different ways to test for two-state…

Biomolecules · Quantitative Biology 2015-05-28 Tristan Bereau , Markus Deserno , Michael Bachmann

The folding ability of a heteropolymer model for proteins subject to Monte Carlo dynamics on a simple cubic lattice is shown to be strongly correlated with the energy gap between the native state and the structurally dissimilar part of the…

Condensed Matter · Physics 2007-05-23 Aaron R. Dinner , Victor Abkevich , Eugene Shakhnovich , Martin Karplus

The recent breakthrough of AlphaFold3 in modeling complex biomolecular interactions, including those between proteins and ligands, nucleotides, or metal ions, creates new opportunities for protein design. In so-called inverse protein…

Biomolecules · Quantitative Biology 2025-07-22 Kai Yi , Kiarash Jamali , Sjors H. W. Scheres

Flexibility is an intrinsic essential feature of protein structures, directly linked to their functions. To this day, most of the prediction methods use the crystallographic data (namely B-factors) as the only indicator of protein's inner…

Many biologically important ligands of proteins are large, flexible, and often charged molecules that bind to extended regions on the protein surface. It is infeasible or expensive to locate such ligands on proteins with standard methods…

Motivation: Protein folding is a dynamic process during which a protein's amino acid sequence undergoes a series of 3-dimensional (3D) conformational changes en route to reaching a native 3D structure; the resulting 3D structural…

Biomolecules · Quantitative Biology 2026-04-09 Aydin Wells , Khalique Newaz , Jennifer Morones , Jianlin Cheng , Tijana Milenković

One of the most intriguing results of single molecule experiments on proteins and nucleic acids is the discovery of functional heterogeneity: the observation that complex cellular machines exhibit multiple, biologically active…

Biomolecules · Quantitative Biology 2022-10-12 Michael Hinczewski , Changbong Hyeon , D. Thirumalai

The simplest approximation of interaction potential between amino-acids in proteins is the contact potential, which defines the effective free energy of a protein conformation by a set of amino acid contacts formed in this conformation.…

Biomolecules · Quantitative Biology 2007-05-23 Jainab Kahtun , Sagar D. Khare , Nikolay V. Dokholyan

Simplified Go models, where only native contacts interact favorably, have proven useful to characterize some aspects of the folding of small proteins. The success of these models is limited by the fact that all residues interact in the same…

Biomolecules · Quantitative Biology 2007-05-23 Ludovico Sutto , Guido Tiana , Ricardo A. Broglia

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

Using a well defined soft model glass in the framework of Molecular Dynamics simulations, the inherent structures are probed by means of a recently developed deformation protocol that aims to capture the Dynamical Heterogeneities (DH), as…

Disordered Systems and Neural Networks · Physics 2013-02-15 F. Leonforte

Native protein folds often have a high degree of symmetry. We study the relationship between the symmetries of native proteins, and their designabilities -- how many different sequences encode a given native structure. Using a…

Statistical Mechanics · Physics 2009-10-31 Tairan Wang , Jonathan Miller , Ned S. Wingreen , Chao Tang , Ken A. Dill

Accurate estimation of mutational effects on protein-protein binding energies is an open problem with applications in structural biology and therapeutic design. Several deep learning predictors for this task have been proposed, but,…

Biomolecules · Quantitative Biology 2025-07-09 Arthur Deng , Karsten Householder , Fang Wu , Sebastian Thrun , K. Christopher Garcia , Brian Trippe

The probability distribution of sequences with maximum entropy that satisfies a given amino acid composition at each site and a given pairwise amino acid frequency at each site pair is a Boltzmann distribution with $\exp(-\psi_N)$, where…

Populations and Evolution · Quantitative Biology 2017-04-04 Sanzo Miyazawa

Understanding the dynamic behavior of proteins is critical to elucidating their functional mechanisms, yet generating realistic, temporally coherent trajectories of protein ensembles remains a significant challenge. In this work, we…

Biomolecules · Quantitative Biology 2025-11-11 Yaoyao Xu , Di Wang , Zihan Zhou , Tianshu Yu , Mingchen Chen