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Related papers: A novel iterative strategy for protein design

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We have considered the problem of protein design based on a model where the contact energy between amino acid residues is fitted phenomenologically using the Miyazawa--Jernigan matrix. Due to the simple form of the contact energy function,…

Soft Condensed Matter · Physics 2007-05-23 Maksim Skorobogatiy , Hong Guo , Martin J. Zuckermann

A new method for sequence optimization in protein models is presented. The approach, which has inherited its basic philosophy from recent work by Deutsch and Kurosky [Phys. Rev. Lett. 76, 323 (1996)] by maximizing conditional probabilities…

Soft Condensed Matter · Physics 2009-10-30 Anders Irbäck , Carsten Peterson , Frank Potthast , Erik Sandelin

In this paper, we consider the computational protein design (CPD) problem, which is usually modeled as a 0/1 programming and is extremely challenging due to its combinatorial properties. We propose an efficient algorithm for solving it.…

Optimization and Control · Mathematics 2024-12-30 Yukai Zheng , Weikun Chen , Qingna Li

Protein design, a grand challenge of the day, involves optimization on a fitness landscape, and leading methods adopt a model-based approach where a model is trained on a training set (protein sequences and fitness) and proposes candidates…

Machine Learning · Computer Science 2024-07-01 Saba Ghaffari , Ehsan Saleh , Alexander G. Schwing , Yu-Xiong Wang , Martin D. Burke , Saurabh Sinha

Therapeutic antibody candidates often require extensive engineering to improve key functional and developability properties before clinical development. This can be achieved through iterative design, where starting molecules are optimized…

Machine Learning · Computer Science 2025-09-23 Aniruddh Raghu , Sebastian Ober , Maxwell Kazman , Hunter Elliott

Computational protein design has a wide variety of applications. Despite its remarkable success, designing a protein for a given structure and function is still a challenging task. On the other hand, the number of solved protein structures…

Quantitative Methods · Quantitative Biology 2018-04-26 Jingxue Wang , Huali Cao , John Z. H. Zhang , Yifei Qi

Only about 1,000 qualitatively different protein folds are believed to exist in nature. Here, we review theoretical studies which suggest that some folds are intrinsically more designable than others, {\it i.e.} are lowest energy states of…

Statistical Mechanics · Physics 2007-05-23 Ned Wingreen , Hao Li , Chao Tang

Algorithms for machine learning-guided design, or design algorithms, use machine learning-based predictions to propose novel objects with desired property values. Given a new design task -- for example, to design novel proteins with high…

Machine Learning · Computer Science 2025-07-04 Clara Fannjiang , Ji Won Park

Protein design is the inverse approach of the three-dimensional (3D) structure prediction for elucidating the relationship between the 3D structures and amino acid sequences. In general, the computation of the protein design involves a…

Biological Physics · Physics 2021-07-14 Tomoei Takahashi , George Chikenji , Kei Tokita

Generative artificial intelligence models learn probability distributions from data and produce novel samples that capture the salient properties of their training sets. Proteins are particularly attractive for such approaches given their…

Biomolecules · Quantitative Biology 2026-02-27 Filippo Stocco , Michele Garibbo , Noelia Ferruz

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

A general strategy is described for finding which amino acid sequences have native states in a desired conformation (inverse design). The approach is used to design sequences of 48 hydrophobic and polar aminoacids on three-dimensional…

Statistical Mechanics · Physics 2009-10-30 C. Micheletti , F. Seno , A. Maritan , J. R. Banavar

The computation of the global minimum energy conformation (GMEC) is an important and challenging topic in structure-based computational protein design. In this paper, we propose a new protein design algorithm based on the AND/OR…

Artificial Intelligence · Computer Science 2015-01-16 Yichao Zhou , Yuexin Wu , Jianyang Zeng

We develop a novel iterative algorithm for locally optimal experimental design under constraints, like budget or performance constraints. It is an adaptive discretization algorithm. In every iteration, a discretized version of the…

Optimization and Control · Mathematics 2026-04-21 Jochen Schmid , Philipp Seufert , Jan Schwientek , Tobias Seidel , Karl-Heinz Küfer

Protein fitness optimization involves finding a protein sequence that maximizes desired quantitative properties in a combinatorially large design space of possible sequences. Recent advances in steering protein generative models (e.g.,…

Biomolecules · Quantitative Biology 2025-10-22 Jason Yang , Wenda Chu , Daniel Khalil , Raul Astudillo , Bruce J. Wittmann , Frances H. Arnold , Yisong Yue

The current capacity of computers makes it possible to perform simulations of small systems with portable, explicit-solvent potentials achieving high degree of accuracy. However, simplified models must be employed to exploit the behaviour…

Biomolecules · Quantitative Biology 2015-06-18 R. Capelli , C. Paissoni , P. Sormanni , G. Tiana

Protein design is a fundamental challenge in biotechnology, aiming to design novel sequences with specific functions within the vast space of possible proteins. Recent advances in deep generative models have enabled function-based protein…

Machine Learning · Computer Science 2025-10-15 Nuowei Liu , Jiahao Kuang , Yanting Liu , Tao Ji , Changzhi Sun , Man Lan , Yuanbin Wu

Proteins are the fundamental macromolecules that play diverse and crucial roles in all living matter and have tremendous implications in healthcare, manufacturing, and biotechnology. Their functions are largely determined by the sequences…

Biomolecules · Quantitative Biology 2024-09-17 Boqiao Lai

We present an analytical method for determining the designability of protein structures. We apply our method to the case of two-dimensional lattice structures, and give a systematic solution for the spectrum of any structure. Using this…

Soft Condensed Matter · Physics 2009-10-31 Edo L. Kussell , Eugene I. Shakhnovich

We propose a novel method for the determination of the effective interaction potential between the amino acids of a protein. The strategy is based on the combination of a new optimization procedure and a geometrical argument, which also…

Soft Condensed Matter · Physics 2009-10-31 Jort van Mourik , Cecilia Clementi , Amos Maritan , Flavio Seno , J. R. Banavar