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Enzyme is the major workhorse to carry out the diverse cellular functions. It catalyzes the biological reactions with a high specificity, with its topology playing a crucial role. For ecologically safe production of numerous bioproducts…

Biomolecules · Quantitative Biology 2021-06-04 Prabha Sankara Narayanan , Ashish Runthala

Designing novel proteins with desired characteristics remains a significant challenge due to the large sequence space and the complexity of sequence-function relationships. Efficient exploration of this space to identify sequences that meet…

Machine Learning · Computer Science 2026-03-04 Erik Hartman , Di Tang , Johan Malmström

DNA and other biopolymers are being investigated as new computing substrates and alternative to silicon-based digital computers. However, the established top-down design of biomolecular interaction networks remains challenging and does not…

Soft Condensed Matter · Physics 2025-11-19 Tanmay Pandey , Petro Feketa , Jan Steinkühler

Protein sequence optimization under tight oracle budgets requires methods that explore vast combinatorial spaces while making each evaluation informative. Existing reinforcement learning and off-policy generative approaches often degrade…

Machine Learning · Computer Science 2026-05-27 Ashima Khanna , Dominik Grimm

We introduce EvoFlows, a variable-length protein sequence-to-sequence modeling approach designed for protein engineering. Existing protein language models are poorly suited for optimization tasks: autoregressive models require full sequence…

Machine Learning · Computer Science 2026-04-09 Nicolas Deutschmann , Constance Ferragu , Jonathan D. Ziegler , Shayan Aziznejad , Eli Bixby

Optimizing discrete black-box functions is key in several domains, e.g. protein engineering and drug design. Due to the lack of gradient information and the need for sample efficiency, Bayesian optimization is an ideal candidate for these…

Existing high-dimensional Bayesian optimization (BO) methods aim to overcome the curse of dimensionality by carefully encoding structural assumptions, from locality to sparsity to smoothness, into the optimization procedure. Surprisingly,…

Machine Learning · Computer Science 2026-04-10 Colin Doumont , Donney Fan , Natalie Maus , Jacob R. Gardner , Henry Moss , Geoff Pleiss

Scientific discovery is increasingly constrained by costly experiments and limited resources, underscoring the need for efficient optimization in AI for science. Bayesian Optimization (BO), though widely adopted for balancing exploration…

Artificial Intelligence · Computer Science 2026-05-19 Xinzhe Yuan , Zhuo Chen , Jianshu Zhang , Huan Xiong , Nanyang Ye , Yuqiang Li , Qinying Gu

Machine learning (ML) is revolutionising drug discovery by expediting the prediction of small molecule properties essential for developing new drugs. These properties -- including absorption, distribution, metabolism and excretion (ADME)--…

Machine Learning · Computer Science 2024-08-02 Alex G. C. de Sá , David B. Ascher

In the era of AI-driven science and engineering, we often want to design discrete objects in silico according to user-specified properties. For example, we may wish to design a protein to bind its target, arrange components within a circuit…

Machine Learning · Computer Science 2026-03-03 James C. Bowden , Sergey Levine , Jennifer Listgarten

Accurate exploration of protein conformational ensembles is essential for uncovering function but remains hard because molecular-dynamics (MD) simulations suffer from high computational costs and energy-barrier trapping. This paper presents…

Machine Learning · Computer Science 2025-11-14 Yuancheng Sun , Yuxuan Ren , Zhaoming Chen , Xu Han , Kang Liu , Qiwei Ye

Intrinsically disordered regions of proteins play a crucial role in cell signaling and drug discovery. However, their high structural flexibility makes accurate residue-level prediction challenging. Existing methods often rely on…

Neural and Evolutionary Computing · Computer Science 2026-03-09 Shaokuan Wang , Pengshan Cui , Yining Qian , An-Yang Lu , Xianpeng Wang

The computation of the global minimum energy conformation (GMEC) is an important and challenging topic in structure-based computational protein design. In this paper, we propose a new protein design algorithm based on the AND/OR…

Artificial Intelligence · Computer Science 2015-01-16 Yichao Zhou , Yuexin Wu , Jianyang Zeng

We consider optimal experimental design (OED) problems in selecting the most informative observation sensors to estimate model parameters in a Bayesian framework. Such problems are computationally prohibitive when the…

Computational Engineering, Finance, and Science · Computer Science 2024-09-10 Jinwoo Go , Peng Chen

Bayesian optimization (BayesOpt) is a gold standard for query-efficient continuous optimization. However, its adoption for drug design has been hindered by the discrete, high-dimensional nature of the decision variables. We develop a new…

Efficient design of genomic perturbation experiments is crucial for accelerating drug discovery and therapeutic target identification, yet exhaustive perturbation of the human genome remains infeasible due to the vast search space of…

Machine Learning · Statistics 2026-03-24 Yanke Li , Tianyu Cui , Tommaso Mansi , Mangal Prakash , Rui Liao

Preferential Bayesian optimization (PBO) is a variant of Bayesian optimization that observes relative preferences (e.g., pairwise comparisons) instead of direct objective values, making it especially suitable for human-in-the-loop…

Machine Learning · Computer Science 2025-05-19 Koki Iwai , Yusuke Kumagae , Yuki Koyama , Masahiro Hamasaki , Masataka Goto

Electromagnetismlike Optimization (EMO) is a global optimization algorithm, particularly well suited to solve problems featuring nonlinear and multimodal cost functions. EMO employs searcher agents that emulate a population of charged…

Artificial Intelligence · Computer Science 2014-05-21 Erik Cuevas , Diego Oliva , Daniel Zaldivar , Marco Perez , Gonzalo Pajares

Protein folding is the intricate process by which a linear sequence of amino acids self-assembles into a unique three-dimensional structure. Protein folding kinetics is the study of pathways and time-dependent mechanisms a protein undergoes…

Machine Learning · Computer Science 2023-09-19 Vijay Arvind. R , Haribharathi Sivakumar , Brindha. R

The tuning of hyperparameters becomes increasingly important as machine learning (ML) models have been extensively applied in data mining applications. Among various approaches, Bayesian optimization (BO) is a successful methodology to tune…

Machine Learning · Computer Science 2022-06-07 Yang Li , Yu Shen , Huaijun Jiang , Tianyi Bai , Wentao Zhang , Ce Zhang , Bin Cui