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Pre-trained models have been successful in many protein engineering tasks. Most notably, sequence-based models have achieved state-of-the-art performance on protein fitness prediction while structure-based models have been used…

Machine Learning · Computer Science 2023-07-25 Antonia Boca , Simon Mathis

This paper presents a novel Differential Evolution algorithm for protein folding optimization that is applied to a three-dimensional AB off-lattice model. The proposed algorithm includes two new mechanisms. A local search is used to improve…

Artificial Intelligence · Computer Science 2018-05-08 Borko Bošković , Janez Brest

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

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

Changes in the extent of local concavity along with changes in surface roughness of binding sites of proteins have long been considered as useful markers to identify functional sites of proteins. However, an algorithm that describes the…

Biomolecules · Quantitative Biology 2011-11-29 Anirban Banerji

The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks…

Statistical Mechanics · Physics 2007-05-23 Johannes Berg , Stana Willmann , Michael Lässig

In this study, the distributions of protein structure classes (or folding types) of experimentally determined structures from a legacy dataset and a comprehensive database (SCOP) are modeled precisely with geometric constructs such as…

Biomolecules · Quantitative Biology 2025-10-21 Boryeu Mao

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

Local and global inference methods have been developed to infer structural contacts from multiple sequence alignments of homologous proteins. They rely on correlations in amino-acid usage at contacting sites. Because homologous proteins…

Biomolecules · Quantitative Biology 2024-12-30 Nicola Dietler , Umberto Lupo , Anne-Florence Bitbol

Several recent works have shown that protein structure can predict site-specific evolutionary sequence variation. In particular, sites that are buried and/or have many contacts with other sites in a structure have been shown to evolve more…

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

Protein evolution involves mutations occurring across a wide range of time scales. In analogy with disordered systems in statistical physics, this dynamical heterogeneity suggests strong correlations between mutations happening at distinct…

Biomolecules · Quantitative Biology 2025-07-15 Saverio Rossi , Leonardo Di Bari , Martin Weigt , Francesco Zamponi

Repeat proteins are made with tandem copies of similar amino acid stretches that fold into elongated architectures. Due to their symmetry, these proteins constitute excellent model systems to investigate how evolution relates to structure,…

Biomolecules · Quantitative Biology 2022-10-12 Ezequiel A. Galpern , Jacopo Marchi , Thierry Mora , Aleksandra M. Walczak , Diego U. Ferreiro

The mechanisms by which a protein's 3D structure can be determined based on its amino acid sequence have long been one of the key mysteries of biophysics. Often simplistic models, such as those derived from geometric constraints, capture…

Biological Physics · Physics 2023-01-02 Nora Molkenthin , J. J. Güven , Steffen Mühle , Antonia S. J. S. Mey

The structure of molecular networks derives from dynamical processes on evolutionary time scales. For protein interaction networks, global statistical features of their structure can now be inferred consistently from several…

Statistical Mechanics · Physics 2007-05-23 Johannes Berg , Michael Lässig , Andreas Wagner

Modern biomedicine is challenged to predict the effects of genetic variation. Systematic functional assays of point mutants of proteins have provided valuable empirical information, but vast regions of sequence space remain unexplored.…

Biomolecules · Quantitative Biology 2017-01-18 Thomas A. Hopf , John B. Ingraham , Frank J. Poelwijk , Michael Springer , Chris Sander , Debora S. Marks

Generative modeling has become a central paradigm in protein research, extending machine learning beyond structure prediction toward sequence design, backbone generation, inverse folding, and biomolecular interaction modeling. However, the…

Machine Learning · Computer Science 2026-03-30 Senura Hansaja Wanasekara , Minh-Duong Nguyen , Xiaochen Liu , Nguyen H. Tran , Ken-Tye Yong

Multimodal approaches that integrate protein structure and sequence have achieved remarkable success in protein-protein interface prediction. However, extending these methods to protein-peptide interactions remains challenging due to the…

Signal Processing · Electrical Eng. & Systems 2025-11-03 Dian Chen , Yunkai Chen , Tong Lin , Sijie Chen , Xiaolin Cheng

Phylogenetics uses alignments of molecular sequence data to learn about evolutionary trees relating species. Along branches, sequence evolution is modelled using a continuous-time Markov process characterised by an instantaneous rate…

The amino acid sequences of proteins provide rich information for inferring distant phylogenetic relationships and for predicting protein functions. Estimating the rate matrix of residue substitutions from amino acid sequences is also…

Biomolecules · Quantitative Biology 2007-05-23 Yan Y. Tseng , Jie Liang