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The ability to computationally generate novel yet physically foldable protein structures could lead to new biological discoveries and new treatments targeting yet incurable diseases. Despite recent advances in protein structure prediction,…

Biomolecules · Quantitative Biology 2022-11-28 Kevin E. Wu , Kevin K. Yang , Rianne van den Berg , James Y. Zou , Alex X. Lu , Ava P. Amini

Structural biology has long been dominated by the one sequence, one structure, one function paradigm, yet many critical biological processes - from enzyme catalysis to membrane transport - depend on proteins that adopt multiple…

Recent advances in coarse-grained lattice and off-lattice protein models are reviewed. The sequence dependence of thermodynamical folding properties are investigated and evidence for non-randomness of the binary sequences of good folders…

High Energy Physics - Lattice · Physics 2015-06-25 C. Peterson

Generating protein sequences that fold into a intended 3D structure is a fundamental step in de novo protein design. De facto methods utilize autoregressive generation, but this eschews higher order interactions that could be exploited to…

Biomolecules · Quantitative Biology 2023-12-06 John J. Yang , Jason Yim , Regina Barzilay , Tommi Jaakkola

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

Protein sequence design must balance designability, defined as the ability to recover a target backbone, with multiple, often competing, developability properties such as solubility, thermostability, and expression. Existing approaches…

Machine Learning · Computer Science 2026-03-11 Xiaoyang Hou , Junqi Liu , Chence Shi , Xin Liu , Zhi Yang , Jian Tang

mRNA technology has revolutionized vaccine development, protein replacement therapies, and cancer immunotherapies, offering rapid production and precise control over sequence and efficacy. However, the inherent instability of mRNA poses…

Biomolecules · Quantitative Biology 2025-03-26 Max Ward , Mary Richardson , Mihir Metkar

Co-optimizing mRNA sequences for both codon optimality and secondary structure is crucial for producing stable and efficacious mRNA therapeutics. Codon optimization, which adjusts nucleotide sequences to enhance translational efficiency,…

Inverse Protein Folding (IPF) is a critical subtask in the field of protein design, aiming to engineer amino acid sequences capable of folding correctly into a specified three-dimensional (3D) conformation. Although substantial progress has…

Computation and Language · Computer Science 2025-05-20 Yanting Li , Jiyue Jiang , Zikang Wang , Ziqian Lin , Dongchen He , Yuheng Shan , Yanruisheng Shao , Jiayi Li , Xiangyu Shi , Jiuming Wang , Yanyu Chen , Yimin Fan , Han Li , Yu Li

Protein folding and design are major biophysical problems, the solution of which would lead to important applications especially in medicine. Here a novel protein model capable of simultaneously provide quantitative protein design and…

Biological Physics · Physics 2015-06-22 Ivan Coluzza

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

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

Protein folding is the intricate process by which a linear sequence of amino acids self-assembles into a unique three-dimensional structure. Protein folding kinetics is the study of pathways and time-dependent mechanisms a protein undergoes…

Machine Learning · Computer Science 2023-09-19 Vijay Arvind. R , Haribharathi Sivakumar , Brindha. R

The Gene or DNA sequence in every cell does not control genetic properties on its own; Rather, this is done through translation of DNA into protein and subsequent formation of a certain 3D structure. The biological function of a protein is…

Computational Engineering, Finance, and Science · Computer Science 2019-05-30 Leila Khalatbari , Mohammad Reza Kangavari , Saeid Hosseini , Hongzhi Yin , Ngai-Man Cheung

Nucleic acid sequence design via codon optimization is a fundamental task with applications across synthetic biology, mRNA therapeutics, and vaccine design. Given a target protein, it is a major open challenge to navigate the…

Quantitative Methods · Quantitative Biology 2026-04-22 Mark Fornace , Christina Wuyan Wang , Michael Lindsey

Most amino acids are encoded by multiple synonymous codons. For an amino acid, some of its synonymous codons are used much more rarely than others. Analyses of positions of such rare codons in protein sequences revealed that rare codons can…

Molecular Networks · Quantitative Biology 2019-07-09 Khalique Newaz , Gabriel Wright , Jacob Piland , Jun Li , Patricia Clark , Scott Emrich , Tijana Milenkovic

Advances in de novo synthesis of DNA and computational gene design methods make possible the customization of genes by direct manipulation of features such as codon bias and mRNA secondary structure. Codon context is another feature…

Data Structures and Algorithms · Computer Science 2015-08-17 Dimitris Papamichail , Hongmei Liu , Vitor Machado , Nathan Gould , J. Robert Coleman , Georgios Papamichail

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

Designing protein sequences that fold into a target 3D structure, known as protein inverse folding, is a fundamental challenge in protein engineering. While recent deep learning methods have achieved impressive performance by recovering…

Biomolecules · Quantitative Biology 2025-06-03 Mengdi Liu , Xiaoxue Cheng , Zhangyang Gao , Hong Chang , Cheng Tan , Shiguang Shan , Xilin Chen

ExpressInHost (https://gitlab.com/a.raguin/expressinhost) is a GTK/C++ based user friendly graphical interface that allows tuning the codon sequence of an mRNA for recombinant protein expression in a host microorganism. Heterologous gene…

Biological Physics · Physics 2022-11-01 AdélaïdeRaguin , Ian Stansfield , Maria Carmen Romano
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