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The number of protein structures is far less than the number of sequences. By imposing simple generic features of proteins (low energy and compaction) on all possible sequences we show that the structure space is sparse compared to the…

Soft Condensed Matter · Physics 2009-10-31 D. Thirumalai , D. K. Klimov

Simple hidden Markov models are proposed for predicting secondary structure of a protein from its amino acid sequence. Since the length of protein conformation segments varies in a narrow range, we ignore the duration effect of length…

Biological Physics · Physics 2007-05-23 Wei-Mou Zheng

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

Proteins populate a manifold in the high-dimensional sequence space whose geometrical structure guides their natural evolution. Leveraging recently-developed structure prediction tools based on transformer models, we first examine the…

Biomolecules · Quantitative Biology 2023-11-13 A. Zambon , R. Zecchina , G. Tiana

In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our…

Quantitative Methods · Quantitative Biology 2014-04-07 Carlo Baldassi , Marco Zamparo , Christoph Feinauer , Andrea Procaccini , Riccardo Zecchina , Martin Weigt , Andrea Pagnani

The structure and function of a protein are determined by its amino acid sequence. While random mutations change a protein's sequence, evolutionary forces shape its structural fold and biological activity. Studies have shown that neutral…

Biomolecules · Quantitative Biology 2024-11-15 Pranav Kantroo , Günter P. Wagner , Benjamin B. Machta

Protein sequence generation for engineering requires samples that are biophysically plausible and, when targeting a family/domain, remain recognizable members while exploring within-family diversity. Current discrete generative models…

Computational Engineering, Finance, and Science · Computer Science 2026-05-25 Langzhang Liang , Ming Yang , Yi Feng , Junfan Li , Shirui Pan , Yinghui Xu , Tianlei Ying , Yizhen Zheng , Zenglin Xu

Amino acid sequence portrays most intrinsic form of a protein and expresses primary structure of protein. The order of amino acids in a sequence enables a protein to acquire a particular stable conformation that is responsible for the…

Machine Learning · Computer Science 2022-08-29 Ashish Ranjan , Md Shah Fahad , David Fernandez-Baca , Akshay Deepak , Sudhakar Tripathi

The growing interest for comparing protein internal dynamics owes much to the realization that protein function can be accompanied or assisted by structural fluctuations and conformational changes. Analogously to the case of functional…

Biomolecules · Quantitative Biology 2012-12-19 C. Micheletti

Proteins power a vast array of functional processes in living cells. The capability to create new proteins with designed structures and functions would thus enable the engineering of cellular behavior and development of protein-based…

Biomolecules · Quantitative Biology 2023-06-08 Yeqing Lin , Mohammed AlQuraishi

Protein is linked to almost every life process. Therefore, analyzing the biological structure and property of protein sequences is critical to the exploration of life, as well as disease detection and drug discovery. Traditional protein…

Machine Learning · Computer Science 2021-12-08 Yijia Xiao , Jiezhong Qiu , Ziang Li , Chang-Yu Hsieh , Jie Tang

We seek to understand the interplay between amino acid sequence and local structure in proteins. Are some amino acids unique in their ability to fit harmoniously into certain local structures? What is the role of sequence in sculpting the…

Biomolecules · Quantitative Biology 2021-01-29 Tatjana Škrbić , Amos Maritan , Achille Giacometti , Jayanth R. Banavar

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

Protein evolution underpins life, and understanding its behavior as a system is of great importance. However, our current models of protein evolution are arguably too simplistic to allow quantitative interpretation and prediction of…

Residue-residue interactions that fold a protein into a unique three-dimensional structure and make it play a specific function impose structural and functional constraints on each residue site. Selective constraints on residue sites are…

Biomolecules · Quantitative Biology 2013-01-18 Sanzo Miyazawa

Proteins are responsible for the most diverse set of functions in biology. The ability to extract information from protein sequences and to predict the effects of mutations is extremely valuable in many domains of biology and medicine.…

Quantitative Methods · Quantitative Biology 2018-01-04 Sam Sinai , Eric Kelsic , George M. Church , Martin A. Nowak

Auto-regulatory feedback loops are one of the most common network motifs. A wide variety of stochastic models have been constructed to understand how the fluctuations in protein numbers in these loops are influenced by the kinetic…

Subcellular Processes · Quantitative Biology 2020-04-22 James Holehouse , Zhixing Cao , Ramon Grima

Global coevolutionary models of homologous protein families, as constructed by direct coupling analysis (DCA), have recently gained popularity in particular due to their capacity to accurately predict residue-residue contacts from sequence…

Quantitative Methods · Quantitative Biology 2019-09-23 Matteo Figliuzzi , Pierre Barrat-Charlaix , Martin Weigt

We study a fundamental problem in structure-based drug design -- generating molecules that bind to specific protein binding sites. While we have witnessed the great success of deep generative models in drug design, the existing methods are…

Biomolecules · Quantitative Biology 2022-11-15 Shitong Luo , Jiaqi Guan , Jianzhu Ma , Jian Peng

The time evolution of the formation probability of native bonds has been studied for designed sequences which fold fast into the native conformation. From this analysis a clear hierarchy of bonds emerge a) local, fast forming highly stable…

Condensed Matter · Physics 2009-10-31 G. Tiana , R. A. Broglia
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