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Protein inverse folding aims to design an amino acid sequence that will fold into a given backbone structure, serving as a central task in protein design. Two main paradigms have been widely explored. Template-based methods exploit…

Machine Learning · Computer Science 2026-03-17 Yiran Zhu , Changxi Chi , Hongxin Xiang , Wenjie Du , Xiaoqi Wang , Jun Xia

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

Designing protein sequences that fold into a target 3-D structure, termed as the inverse folding problem, is central to protein engineering. However, it remains challenging due to the vast sequence space and the importance of local…

Quantitative Methods · Quantitative Biology 2026-03-17 Sazan Mahbub , Souvik Kundu , Eric P. Xing

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

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

This paper presents a method of reconstruction a primary structure of a protein that folds into a given geometrical shape. This method predicts the primary structure of a protein and restores its linear sequence of amino acids in the…

Quantitative Methods · Quantitative Biology 2017-01-04 Andrii Riazanov , Mikhail Karasikov , Sergei Grudinin

Generating protein sequences conditioned on protein structures is an impactful technique for protein engineering. When synthesizing engineered proteins, they are commonly translated into DNA and expressed in an organism such as yeast. One…

Machine Learning · Computer Science 2024-09-27 Hannes Stark , Umesh Padia , Julia Balla , Cameron Diao , George Church

Inverse protein folding is a fundamental task in computational protein design, which aims to design protein sequences that fold into the desired backbone structures. While the development of machine learning algorithms for this task has…

Machine Learning · Computer Science 2024-11-05 Yiheng Zhu , Jialu Wu , Qiuyi Li , Jiahuan Yan , Mingze Yin , Wei Wu , Mingyang Li , Jieping Ye , Zheng Wang , Jian Wu

We apply a new approach to the reverse protein folding problem. Our method uses a minimization function in the design process which is different from the energy function used for folding. For a lattice model, we show that this new approach…

Condensed Matter · Physics 2009-10-28 J. M. Deutsch , Tanya Kurosky

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

Inverse problems are ubiquitous in nature, arising in almost all areas of science and engineering ranging from geophysics and climate science to astrophysics and biomechanics. One of the central challenges in solving inverse problems is…

Machine Learning · Statistics 2022-09-21 Dhruv V Patel , Deep Ray , Assad A Oberai

Excitement at the prospect of using data-driven generative models to sample configurational ensembles of biomolecular systems stems from the extraordinary success of these models on a diverse set of high-dimensional sampling tasks. Unlike…

Statistical Mechanics · Physics 2024-02-06 Shriram Chennakesavalu , Grant M. Rotskoff

Recent advances in geometric deep learning and generative modeling have enabled the design of novel proteins with a wide range of desired properties. However, current state-of-the-art approaches are typically restricted to generating…

Biomolecules · Quantitative Biology 2025-08-26 Vsevolod Viliuga , Leif Seute , Nicolas Wolf , Simon Wagner , Arne Elofsson , Jan Stühmer , Frauke Gräter

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 Bayesian approach to solving inverse problems relies on the choice of a prior. This critical ingredient allows the formulation of expert knowledge or physical constraints in a probabilistic fashion and plays an important role for the…

Machine Learning · Statistics 2022-11-08 Manuel Marschall , Gerd Wübbeler , Franko Schmähling , Clemens Elster

Directed evolution is an iterative laboratory process of designing proteins with improved function by iteratively synthesizing new protein variants and evaluating their desired property with expensive and time-consuming biochemical…

Machine Learning · Computer Science 2025-09-08 Matouš Soldát , Jiří Kléma

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

Many researches have been working on the protein folding problem from more than half century. Protein folding is indeed one of the major unsolved problems in science. In this work, we discuss a model for the simulation of protein…

Optimization and Control · Mathematics 2008-11-20 A. Mucherino , O. Seref , P. M. Pardalos

Incorporating a deep generative model as the prior distribution in inverse problems has established substantial success in reconstructing images from corrupted observations. Notwithstanding, the existing optimization approaches use gradient…

Machine Learning · Computer Science 2023-01-31 Tianci Liu , Tong Yang , Quan Zhang , Qi Lei

We present InvMSAFold, an inverse folding method for generating protein sequences that is optimized for diversity and speed. For a given structure, InvMSAFold generates the parameters of a probability distribution over the space of…

Quantitative Methods · Quantitative Biology 2025-05-30 Luca Alessandro Silva , Barthelemy Meynard-Piganeau , Carlo Lucibello , Christoph Feinauer
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