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Protein sequence design, determined by amino acid sequences, are essential to protein engineering problems in drug discovery. Prior approaches have resorted to evolutionary strategies or Monte-Carlo methods for protein design, but often…

Large-scale networked multi-agent systems increasingly underpin critical infrastructure, yet their collective behavior can drift toward undesirable emergent norms such as collusion, resource hoarding, and implicit unfairness. We present the…

Multiagent Systems · Computer Science 2026-03-20 Saad Alqithami

Effective reasoning is crucial to solving complex mathematical problems. Recent large language models (LLMs) have boosted performance by scaling test-time computation through long chain-of-thought reasoning. However, transformer-based…

Machine Learning · Computer Science 2025-09-10 Junxiong Wang , Wen-Ding Li , Daniele Paliotta , Daniel Ritter , Alexander M. Rush , Tri Dao

MOTIVATION: Proteins fold into complex structures that are crucial for their biological functions. Experimental determination of protein structures is costly and therefore limited to a small fraction of all known proteins. Hence, different…

Biomolecules · Quantitative Biology 2018-04-18 David Menéndez Hurtado , Karolis Uziela , Arne Elofsson

Structure-based protein design has attracted increasing interest, with numerous methods being introduced in recent years. However, a universally accepted method for evaluation has not been established, since the wet-lab validation can be…

Quantitative Methods · Quantitative Biology 2023-12-04 Chuanrui Wang , Bozitao Zhong , Zuobai Zhang , Narendra Chaudhary , Sanchit Misra , Jian Tang

The analysis of data from multiple experiments, such as observations of several individuals, is commonly approached using mixed-effects models, which account for variation between individuals through hierarchical representations. This makes…

Computation · Statistics 2026-03-05 Henrik Häggström , Sebastian Persson , Marija Cvijovic , Umberto Picchini

Recursive max-linear vectors model causal dependence between its components by expressing each node variable as a max-linear function of its parental nodes in a directed acyclic graph and some exogenous innovation. Motivated by extreme…

Methodology · Statistics 2019-12-10 Claudia Klüppelberg , Mario Krali

This paper presents an advancement to an approach for model-independent surrogate-based optimization with adaptive batch sampling, known as Adaptive Model Refinement (AMR). While the original AMR method provides unique decisions with…

Optimization and Control · Mathematics 2019-06-04 Payam Ghassemi , Sumeet Sanjay Lulekar , Souma Chowdhury

Prediction of protein structures using computational approaches has been explored for over two decades, paving a way for more focused research and development of algorithms in comparative modelling, ab intio modelling and structure…

Quantitative Methods · Quantitative Biology 2020-05-19 Surbhi Dhingra , Ramanathan Sowdhamini , Frédéric Cadet , Bernard Offmann

We explore optimally training protein language models, an area of significant interest in biological research where guidance on best practices is limited. Most models are trained with extensive compute resources until performance gains…

Machine Learning · Computer Science 2024-11-05 Xingyi Cheng , Bo Chen , Pan Li , Jing Gong , Jie Tang , Le Song

Recently described stochastic models of protein evolution have demonstrated that the inclusion of structural information in addition to amino acid sequences leads to a more reliable estimation of evolutionary parameters. We present a…

Populations and Evolution · Quantitative Biology 2020-09-22 Michael Golden , Eduardo García-Portugués , Michael Sørensen , Kanti V. Mardia , Thomas Hamelryck , Jotun Hein

The rapid evolution of molecular dynamics (MD) methods, including machine-learned dynamics, has outpaced the development of standardized tools for method validation. Objective comparison between simulation approaches is often hindered by…

Recent years have seen significant advancements in foundation models through generative pre-training, yet algorithmic innovation in this space has largely stagnated around autoregressive models for discrete signals and diffusion models for…

Machine Learning · Computer Science 2025-03-12 Jiaming Song , Linqi Zhou

Proteins are inherently multiscale physical systems whose functional properties emerge from coordinated structural organization across multiple spatial resolutions, ranging from atomic interactions to global fold topology. However, existing…

Machine Learning · Computer Science 2026-05-13 Viet Thanh Duy Nguyen , John K. Johnstone , Truong-Son Hy

Deep learning models have demonstrated remarkable performance across various computer vision tasks, yet their vulnerability to distribution shifts remains a critical challenge. Despite sophisticated neural network architectures, existing…

Computer Vision and Pattern Recognition · Computer Science 2025-01-14 Hafiz Mughees Ahmad , Dario Morle , Afshin Rahimi

Molecular Dynamics (MD) is a powerful computational microscope for probing protein functions. However, the need for fine-grained integration and the long timescales of biomolecular events make MD computationally expensive. To address this,…

Machine Learning · Computer Science 2026-03-30 Kacper Kapuśniak , Cristian Gabellini , Michael Bronstein , Prudencio Tossou , Francesco Di Giovanni

Protein activity is a significant characteristic for recombinant proteins which can be used as biocatalysts. High activity of proteins reduces the cost of biocatalysts. A model that can predict protein activity from amino acid sequence is…

Quantitative Methods · Quantitative Biology 2018-07-23 X. Han , X. Wang , K. Zhou

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

We introduce Adjoint Sampling, a highly scalable and efficient algorithm for learning diffusion processes that sample from unnormalized densities, or energy functions. It is the first on-policy approach that allows significantly more…

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
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