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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

The protein design problem involves finding polypeptide sequences folding into a given threedimensional structure. Its rigorous algorithmic solution is computationally demanding, involving a nested search in sequence and structure spaces.…

Quantum Physics · Physics 2024-07-11 Veronica Panizza , Philipp Hauke , Cristian Micheletti , Pietro Faccioli

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

Computational protein design aims at constructing novel or improved functions on the structure of a given protein backbone and has important applications in the pharmaceutical and biotechnical industry. The underlying combinatorial…

Data Structures and Algorithms · Computer Science 2011-03-29 Stefan Canzar , Nora C. Toussaint , Gunnar W. Klau

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

Proteins are sequences of amino acids that serve as the basic building blocks of living organisms. Despite rapidly growing databases documenting structural and functional information for various protein sequences, our understanding of…

Biomolecules · Quantitative Biology 2025-01-06 Weihang Dai

Proteins perform critical processes in all living systems: converting solar energy into chemical energy, replicating DNA, as the basis of highly performant materials, sensing and much more. While an incredible range of functionality has…

Biomolecules · Quantitative Biology 2021-09-29 Leonardo V. Castorina , Rokas Petrenas , Kartic Subr , Christopher W. Wood

We propose and discuss a novel strategy for protein design. The method is based on recent theoretical advancements which showed the importance to treat carefully the conformational free energy of designed sequences. In this work we show how…

Statistical Mechanics · Physics 2009-10-31 A. Rossi , A. Maritan , C. Micheletti

Spatially proximate amino acids in a protein tend to coevolve. A protein's three-dimensional (3D) structure hence leaves an echo of correlations in the evolutionary record. Reverse engineering 3D structures from such correlations is an open…

Quantitative Methods · Quantitative Biology 2013-01-15 Magnus Ekeberg , Cecilia Lövkvist , Yueheng Lan , Martin Weigt , Erik Aurell

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

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

We present a detailed study of the performance and reliability of design procedures based on energy minimization. The analysis is carried out for model proteins where exact results can be obtained through exhaustive enumeration. The…

Statistical Mechanics · Physics 2007-05-23 Cristian Micheletti , Amos Maritan

We review the recent progress in computational approaches to protein design which builds on advances in statistical-mechanical protein folding theory. In particular, we evaluate the degeneracy of the protein code (i.e. how many sequences…

Condensed Matter · Physics 2007-05-23 E. I. Shakhnovich

Deep learning is catalyzing a scientific revolution fueled by big data, accessible toolkits, and powerful computational resources, impacting many fields including protein structural modeling. Protein structural modeling, such as predicting…

Biomolecules · Quantitative Biology 2020-07-17 Wenhao Gao , Sai Pooja Mahajan , Jeremias Sulam , Jeffrey J. Gray

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

Proteins are miniature machines whose function depends on their three-dimensional (3D) structure. Determining this structure computationally remains an unsolved grand challenge. A major bottleneck involves selecting the most accurate…

Quantitative Methods · Quantitative Biology 2020-11-30 Stephan Eismann , Patricia Suriana , Bowen Jing , Raphael J. L. Townshend , Ron O. Dror

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

Protein design has the potential to revolutionize biotechnology and medicine. While most efforts have focused on proteins with well-defined structures, increased recognition of the functional significance of intrinsically disordered…

Biomolecules · Quantitative Biology 2025-09-17 Giulio Tesei , Francesco Pesce , Kresten Lindorff-Larsen

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 sequence design is a challenging problem in protein engineering, which aims to discover novel proteins with useful biological functions. Directed evolution is a widely-used approach for protein sequence design, which mimics the…

Machine Learning · Computer Science 2023-03-21 Chuanjiao Zong
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