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Protein sequences serve as a natural record of the evolutionary constraints that shape their functional structures. We show that it is possible to use only sequence information to go beyond predicting native structures and global stability…

Biomolecules · Quantitative Biology 2025-07-02 Ezequiel A. Galpern , Ernesto A. Roman , Diego U. Ferreiro

Inverse protein folding is challenging due to its inherent one-to-many mapping characteristic, where numerous possible amino acid sequences can fold into a single, identical protein backbone. This task involves not only identifying viable…

Quantitative Methods · Quantitative Biology 2023-11-08 Kai Yi , Bingxin Zhou , Yiqing Shen , Pietro Liò , Yu Guang Wang

This review is a tutorial for scientists interested in the problem of protein structure prediction, particularly those interested in using coarse-grained molecular dynamics models that are optimized using lessons learned from the energy…

Biomolecules · Quantitative Biology 2014-01-06 N. P. Schafer , B. L. Kim , W. Zheng , P. G. Wolynes

We propose an automated protocol for designing the energy landscape of a protein energy function by optimizing its parameters. The parameters are optimized so that not only the global minimum energy conformation becomes native-like, but…

Soft Condensed Matter · Physics 2007-05-23 Julian Lee , Seung-Yeon Kim , Jooyoung Lee

This paper investigates fundamental properties of nonlinear binary codes by looking at the codebook matrix not row-wise (codewords), but column-wise. The family of weak flip codes is presented and shown to contain many beautiful properties.…

Information Theory · Computer Science 2017-11-10 Hsuan-Yin Lin , Stefan M. Moser , Po-Ning Chen

By removing irrelevant and redundant features, feature selection aims to find a good representation of the original features. With the prevalence of unlabeled data, unsupervised feature selection has been proven effective in alleviating the…

Machine Learning · Computer Science 2024-03-25 Ziyuan Lin , Deanna Needell

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

RNA design aims to find a sequence that folds with highest probability into a designated target structure. However, certain structures are undesignable, meaning no sequence can fold into the target structure under the default (Turner) RNA…

Data Structures and Algorithms · Computer Science 2025-05-06 Tianshuo Zhou , Wei Yu Tang , Apoorv Malik , David H. Mathews , Liang Huang

Lattice models, for their coarse-grained nature, are best suited for the study of the ``designability problem'', the phenomenon in which most of the about 16,000 proteins of known structure have their native conformations concentrated in a…

Biological Physics · Physics 2009-11-07 C. T. Shih , Z. Y. Su , J. F. Gwan , B. L. Hao , C. H. Hsieh , J. L. Lo. , H. C. Lee

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

Computational protein design has the potential to deliver novel molecular structures, binders, and catalysts for myriad applications. Recent neural graph-based models that use backbone coordinate-derived features show exceptional…

Biomolecules · Quantitative Biology 2022-04-28 Alex J. Li , Vikram Sundar , Gevorg Grigoryan , Amy E. Keating

The design of novel proteins has many applications but remains an attritional process with success in isolated cases. Meanwhile, deep learning technologies have exploded in popularity in recent years and are increasingly applicable to…

Biomolecules · Quantitative Biology 2018-11-07 Joe G Greener , Lewis Moffat , David T Jones

Computational protein design facilitates discovery of novel proteins with prescribed structure and functionality. Exciting designs were recently reported using novel data-driven methodologies that can be roughly divided into two categories:…

Biological Physics · Physics 2023-03-28 Cyril Malbranke , David Bikard , Simona Cocco , Rémi Monasson , Jérôme Tubiana

We study the fundamental problem of selecting optimal features for model construction. This problem is computationally challenging on large datasets, even with the use of greedy algorithm variants. To address this challenge, we extend the…

Computational protein design (CPD) offers transformative potential for bioengineering, but current deep CPD models, focused on universal domains, struggle with function-specific designs. This work introduces a novel CPD paradigm tailored…

Quantitative Methods · Quantitative Biology 2024-11-28 Jiangbin Zheng , Ge Wang , Han Zhang , Stan Z. Li

Many applications of machine learning methods involve an iterative protocol in which data are collected, a model is trained, and then outputs of that model are used to choose what data to consider next. For example, one data-driven approach…

Machine Learning · Computer Science 2025-04-07 Clara Fannjiang , Stephen Bates , Anastasios N. Angelopoulos , Jennifer Listgarten , Michael I. Jordan

Geometric deep learning has recently achieved great success in non-Euclidean domains, and learning on 3D structures of large biomolecules is emerging as a distinct research area. However, its efficacy is largely constrained due to the…

Machine Learning · Computer Science 2023-10-31 Fang Wu , Lirong Wu , Dragomir Radev , Jinbo Xu , Stan Z. Li

Barrier potentials gained popularity as a means for robust contact handling in physical modeling and for modeling self-avoiding shapes. The key to the success of these approaches is adherence to geometric constraints, i.e., avoiding…

Graphics · Computer Science 2025-05-29 Zizhou Huang , Max Paik , Zachary Ferguson , Daniele Panozzo , Denis Zorin

Kernel-based methods enjoy powerful generalization capabilities in handling a variety of learning tasks. When such methods are provided with sufficient training data, broadly-applicable classes of nonlinear functions can be approximated…

Machine Learning · Statistics 2017-12-29 Fatemeh Sheikholeslami , Dimitris Berberidis , Georgios B. Giannakis

Choosing a deep neural network architecture is a fundamental problem in applications that require balancing performance and parameter efficiency. Standard approaches rely on ad-hoc engineering or computationally expensive validation on a…

Machine Learning · Computer Science 2020-04-01 Calvin Murdock , Simon Lucey