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Geometric deep learning has recently achieved great success in non-Euclidean domains, and learning on 3D structures of large biomolecules is emerging as a distinct research area. However, its efficacy is largely constrained due to the…

Machine Learning · Computer Science 2023-10-31 Fang Wu , Lirong Wu , Dragomir Radev , Jinbo Xu , Stan Z. Li

Protein-protein docking is crucial for understanding how proteins interact. Numerous docking tools have been developed to discover possible conformations of two interacting proteins. However, the reliability and success of these docking…

Biomolecules · Quantitative Biology 2025-11-18 Azam Shirali , Vitalii Stebliankin , Jimeng Shi , Prem Chapagain , Giri Narasimhan

Recent advances in coarse-grained lattice and off-lattice protein models are reviewed. The sequence dependence of thermodynamical folding properties are investigated and evidence for non-randomness of the binary sequences of good folders…

High Energy Physics - Lattice · Physics 2015-06-25 C. Peterson

Proteins exist as a dynamic ensemble of multiple conformations, and these motions are often crucial for their functions. However, current structure prediction methods predominantly yield a single conformation, overlooking the conformational…

Biomolecules · Quantitative Biology 2025-06-18 Advaith Maddipatla , Nadav Bojan Sellam , Meital Bojan , Sanketh Vedula , Paul Schanda , Ailie Marx , Alex M. Bronstein

Structural prediction of protein-protein interactions is important to understand the molecular basis of cellular interactions, but it still faces major challenges when significant conformational changes are present. We propose a generative…

Computational Engineering, Finance, and Science · Computer Science 2025-09-26 Rujie Yin , Yang Shen

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

The function of protein, RNA, and DNA is modulated by fast, dynamic exchanges between three-dimensional conformations. Conformational sampling of biomolecules with exact and nullspace inverse kinematics, using rotatable bonds as revolute…

Robotics · Computer Science 2016-07-27 Rasmus Fonseca , Dominik Budday , Henry van den Bedem

Deep generative models have recently been proposed for sampling protein conformations from the Boltzmann distribution, as an alternative to often prohibitively expensive Molecular Dynamics simulations. However, current state-of-the-art…

Biomolecules · Quantitative Biology 2025-11-13 Nicolas Wolf , Leif Seute , Vsevolod Viliuga , Simon Wagner , Jan Stühmer , Frauke Gräter

Recent advancements in immune sequencing and experimental techniques are generating extensive T cell receptor (TCR) repertoire data, enabling the development of models to predict TCR binding specificity. Despite the computational challenges…

Quantitative Methods · Quantitative Biology 2024-07-24 Anna Weber , Aurélien Pélissier , María Rodríguez Martínez

Molecular dynamics simulations of folding in an off-lattice protein model reveal a nucleation scenario, in which a few well-defined contacts are formed with high probability in the transition state ensemble of conformations. Their…

Statistical Mechanics · Physics 2009-09-25 Nikolay V. Dokholyan , Sergey V. Buldyrev , H. Eugene Stanley , Eugene I. Shakhnovich

As protein informatics advances rapidly, the demand for enhanced predictive accuracy, structural analysis, and functional understanding has intensified. Transformer models, as powerful deep learning architectures, have demonstrated…

Machine Learning · Computer Science 2025-05-28 Xiaowen Ling , Zhiqiang Li , Yanbin Wang , Zhuhong You

Complexes of physically interacting proteins are one of the fundamental functional units responsible for driving key biological mechanisms within the cell. Their identification is therefore necessary not only to understand complex formation…

Computational Engineering, Finance, and Science · Computer Science 2012-11-27 Sriganesh Srihari , Hon Wai Leong

Deep generative models that learn from the distribution of natural protein sequences and structures may enable the design of new proteins with valuable functions. While the majority of today's models focus on generating either sequences or…

Biomolecules · Quantitative Biology 2024-10-03 Chentong Wang , Sarah Alamdari , Carles Domingo-Enrich , Ava Amini , Kevin K. Yang

Data-driven modeling based on Machine Learning (ML) is becoming a central component of protein engineering workflows. This perspective presents the elements necessary to develop effective, reliable, and reproducible ML models, and a set of…

Biomolecules · Quantitative Biology 2025-07-11 Fabio Herrera-Rocha , David Medina-Ortiz , Fabian Mauz , Juergen Pleiss , Mehdi D. Davari

Advancements in AI for science unlocks capabilities for critical drug discovery tasks such as protein-ligand binding affinity prediction. However, current models overfit to existing oversimplified datasets that does not represent naturally…

Machine Learning · Computer Science 2025-12-02 Ming-Hsiu Wu , Ziqian Xie , Shuiwang Ji , Degui Zhi

Normal mode analysis offers an efficient way of modeling the conformational flexibility of protein structures. Simple models defined by contact topology, known as elastic network models, have been used to model a variety of systems, but the…

Biomolecules · Quantitative Biology 2007-05-23 Dmitry A. Kondrashov , Adam W. Van Wynsberghe , Ryan M. Bannen , Qiang Cui , George N. Phillips

De novo ligand design is a fundamental task that seeks to generate protein or molecule candidates that can effectively dock with protein receptors and achieve strong binding affinity entirely from scratch. It holds paramount significance…

Machine Learning · Computer Science 2025-10-13 Zekai Chen , Xunkai Li , Sirui Zhang , Henan Sun , Jia Li , Zhenjun Li , Bing Zhou , Rong-Hua Li , Guoren Wang

Proteolysis targeting chimeras (PROTACs) are small molecules that trigger the breakdown of traditionally ``undruggable'' proteins by binding simultaneously to their targets and degradation-associated proteins. A key challenge in their…

Biomolecules · Quantitative Biology 2024-05-14 Bo Qiang , Wenxian Shi , Yuxuan Song , Menghua Wu

Despite the importance of a thermodynamically stable structure with a conserved fold for protein function, almost all evolutionary models neglect site-site correlations that arise from physical interactions between neighboring amino acid…

Populations and Evolution · Quantitative Biology 2013-12-04 Andrew J. Bordner , Hans D. Mittelmann

Molecular dynamics simulations are an important tool for describing the evolution of a chemical system with time. However, these simulations are inherently held back either by the prohibitive cost of accurate electronic structure theory…

Chemical Physics · Physics 2018-12-20 Michael Gastegger , Philipp Marquetand
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