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Natural protein sequences somehow encode the structural forms that these molecules adopt. Recent developments in structure-prediction are agnostic to the mechanisms by which proteins fold and represent them as static objects. However, the…

Biomolecules · Quantitative Biology 2025-05-26 Ezequiel A. Galpern , Federico Caamaño , Diego U. Ferreiro

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

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

Protein activity is a significant characteristic for recombinant proteins which can be used as biocatalysts. High activity of proteins reduces the cost of biocatalysts. A model that can predict protein activity from amino acid sequence is…

Quantitative Methods · Quantitative Biology 2018-07-23 X. Han , X. Wang , K. Zhou

Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness…

Populations and Evolution · Quantitative Biology 2015-05-30 Alexander E. Lobkovsky , Yuri I. Wolf , Eugene V. Koonin

Rigidity analysis using the "pebble game" can usefully be applied to protein crystal structures to obtain information on protein folding, assembly and the structure-function relationship. However, previous work using this technique has not…

Molecular Networks · Quantitative Biology 2009-09-25 Stephen A. Wells , J. Emilio Jimenez-Roldan , Rudolf A. Römer

We investigate fundamental decisions in the design of instruction set architectures for linear genetic programs that are used as both model systems in evolutionary biology and underlying solution representations in evolutionary computation.…

Neural and Evolutionary Computing · Computer Science 2013-12-30 David M. Bryson , Charles Ofria

Proteins have evolved through mutations, amino acid substitutions, since life appeared on Earth, some 109 years ago. The study of these phenomena has been of particular significance because of their impact on protein stability, function,…

Biomolecules · Quantitative Biology 2023-10-25 Jorge A. Vila

We review and further develop an analytical model that describes how thermodynamic constraints on the stability of the native state influence protein evolution in a site-specific manner. To this end, we represent both protein sequences and…

Biomolecules · Quantitative Biology 2007-05-23 Ugo Bastolla , Markus Porto , H. Eduardo Roman , Michele Vendruscolo

We simulate the evolution of a protein-like sequence subject to point mutations, imposing conservation of the ground state, thermodynamic stability and fast folding. Our model is aimed at describing neutral evolution of natural proteins. We…

Statistical Mechanics · Physics 2009-10-31 Ugo Bastolla , Michele Vendruscolo , H. Eduardo Roman

We present a simple theory that uses thermodynamic parameters to predict the probability that a protein retains the wildtype structure after one or more random amino acid substitutions. Our theory predicts that for large numbers of…

Biomolecules · Quantitative Biology 2009-11-10 Jesse D. Bloom , Jonathan J. Silberg , Claus O. Wilke , D. Allan Drummond , Christoph Adami , Frances H. Arnold

Generative machine learning models are increasingly being used to design novel proteins for therapeutic and biotechnological applications. However, the current methods mostly focus on the design of proteins with a fixed backbone structure,…

Biomolecules · Quantitative Biology 2025-03-04 Petr Kouba , Joan Planas-Iglesias , Jiri Damborsky , Jiri Sedlar , Stanislav Mazurenko , Josef Sivic

The structure of a protein is crucial in determining its functionality, and is much more conserved than sequence during evolution. A key task in structural biology is to compare protein structures in order to determine evolutionary…

Methodology · Statistics 2019-11-06 Christopher Fallaize , Peter Green , Kanti Mardia , Stuart Barber

Protein function does not solely depend on structure but often relies on dynamical transitions between distinct conformations. Despite this fact, our ability to characterize or predict protein dynamics is substantially less developed…

Statistical Mechanics · Physics 2026-05-08 Michael A. Sauer , Souvik Mondal , Brandon Neff , Sthitadhi Maiti , Matthias Heyden

Recent advancements in protein docking site prediction have highlighted the limitations of traditional rigid docking algorithms, like PIPER, which often neglect critical stochastic elements such as solvent-induced fluctuations. These…

Quantitative Methods · Quantitative Biology 2024-12-02 Nanjie Chen , Dongliang Yu , Dmitri Beglov , Mark Kon , Julio Enrique Castrillon-Candas

Proteins are the basic building blocks of life. They usually perform functions by folding to a particular structure. Understanding the folding process could help the researchers to understand the functions of proteins and could also help to…

Computational Engineering, Finance, and Science · Computer Science 2015-10-21 Jianzhu Ma

The structure and function of a protein are determined by its amino acid sequence. While random mutations change a protein's sequence, evolutionary forces shape its structural fold and biological activity. Studies have shown that neutral…

Biomolecules · Quantitative Biology 2024-11-15 Pranav Kantroo , Günter P. Wagner , Benjamin B. Machta

Mapping between sequence and structure is currently an open problem in structural biology. Despite many experimental and computational efforts it is not clear yet how the structure is encoded in the sequence. Answering this question may…

Biomolecules · Quantitative Biology 2013-10-08 Iddo Friedberg

Emergence of new protein structures has proved difficult to trace in nature and engineer in the laboratory. However, one aspect of structure evolution has proved immensely helpful for determining the three-dimensional structure of proteins…

Populations and Evolution · Quantitative Biology 2017-05-24 Amy I. Gilson , Ahmee Marshall-Christensen , Jeong-Mo Choi , Eugene I. Shakhnovich

An accurate estimation of the Protein Space size, in light of the factors that govern it, is a long-standing problem and of paramount importance in evolutionary biology, since it determines the nature of protein evolvability. A simple…

Populations and Evolution · Quantitative Biology 2020-08-27 Jorge A. Vila