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Proteins can exhibit dynamic structural flexibility as they carry out their functions, especially in binding regions that interact with other molecules. For the key SARS-CoV-2 spike protein that facilitates COVID-19 infection, studies have…

Applications · Statistics 2022-02-08 Samuel W. K. Wong

A general adaptive approach rooted in stratified sampling (SS) is proposed for sample-based uncertainty quantification (UQ). To motivate its use in this context the space-filling, orthogonality, and projective properties of SS are compared…

Methodology · Statistics 2015-12-14 Michael D. Shields , Kirubel Teferra , Adam Hapij , Raymond P. Daddazio

Ranked set sampling (RSS) is a stratified sampling method that improves efficiency over simple random sampling (SRS) by utilizing auxiliary information for ranking and stratification. While balanced RSS (BRSS) assumes equal allocation…

Methodology · Statistics 2025-09-03 Chul Moon , Soohyun Ahn

Protein structures and functions are determined by a contiguous arrangement of amino acid sequences. Designing novel protein sequences and structures with desired geometry and functions is a complex task with large state spaces. Here we…

Chemical Physics · Physics 2022-09-01 Xeerak Agha , Nihang Fu , Jianjun Hu

Spider silks are remarkable materials characterized by superb mechanical properties such as strength, extensibility and lightweightedness. Yet, to date, limited models are available to fully explore sequence-property relationships for…

Materials Science · Physics 2023-10-20 Wei Lu , David L. Kaplan , Markus J. Buehler

Evolution is an extraordinary engine for enzymatic diversity, yet the chemistry it has explored remains a narrow slice of what DNA can encode. Deep generative models can design new proteins that bind ligands, but none have created enzymes…

Latent Space (LS) network models project the nodes of a network on a $d$-dimensional latent space to achieve dimensionality reduction of the network while preserving its relevant features. Inference is often carried out within a Markov…

Computation · Statistics 2024-08-23 Roberto Casarin , Antonio Peruzzi

Recently, deep learning has made rapid progress in antibody design, which plays a key role in the advancement of therapeutics. A dominant paradigm is to train a model to jointly generate the antibody sequence and the structure as a…

Quantitative Methods · Quantitative Biology 2025-01-20 Nayoung Kim , Minsu Kim , Sungsoo Ahn , Jinkyoo Park

The biological functions of proteins often depend on dynamic structural ensembles. In this work, we develop a flow-based generative modeling approach for learning and sampling the conformational landscapes of proteins. We repurpose highly…

Biomolecules · Quantitative Biology 2024-09-04 Bowen Jing , Bonnie Berger , Tommi Jaakkola

Proteins are macromolecules that perform essential functions in all living organisms. Designing novel proteins with specific structures and desired functions has been a long-standing challenge in the field of bioengineering. Existing…

Biomolecules · Quantitative Biology 2023-03-03 Chence Shi , Chuanrui Wang , Jiarui Lu , Bozitao Zhong , Jian Tang

Predicting stable and metastable structures is central to molecular and materials discovery, but remains limited by the cost of searching high-dimensional energy landscapes. Deep generative models offer efficient structure sampling, yet…

Artificial Intelligence · Computer Science 2026-05-26 Yifang Qin , Yu Shi , Junfu Tan , Chang Liu , Ming Zhang , Ziheng Lu

High-quality training datasets are crucial for the development of effective protein design models, but existing synthetic datasets often include unfavorable sequence-structure pairs, impairing generative model performance. We leverage…

Reinforcement learning (RL) has been pivotal in enhancing the reasoning capabilities of large language models (LLMs), but it often suffers from limited exploration and entropy collapse, where models exploit a narrow set of solutions,…

Machine Learning · Computer Science 2025-10-20 Shijia Kang , Muhan Zhang

The Robust Satisficing (RS) model is an emerging approach to robust optimization, offering streamlined procedures and robust generalization across various applications. However, the statistical theory of RS remains unexplored in the…

Machine Learning · Statistics 2024-06-03 Zhiyi Li , Yunbei Xu , Ruohan Zhan

In real-world scenarios, pixel-level labeling is not always available. Sometimes, we need a semantic segmentation network, and even a visual encoder can have a high compatibility, and can be trained using various types of feedback beyond…

Computer Vision and Pattern Recognition · Computer Science 2025-05-26 Xie Ting , Ye Huang , Zhilin Liu , Lixin Duan

Reservoir Computing (RC) is a time-efficient computational paradigm derived from Recurrent Neural Networks (RNNs). The Simple Cycle Reservoir (SCR) is an RC model that stands out for its minimalistic design, offering extremely low…

Neural and Evolutionary Computing · Computer Science 2025-04-22 Ziqiang Li , Robert Simon Fong , Kantaro Fujiwara , Kazuyuki Aihara , Gouhei Tanaka

Developing an MR sequence is challenging and remains largely constrained by human intuition. Recently, AI-driven approaches have been proposed; however, most require an initial sequence for parameter optimization or extensive training…

Artificial Intelligence · Computer Science 2026-04-17 Rokgi Hong , Hongjun An , Sooyeon Ji , Jongho Lee

Designing novel functional proteins crucially depends on accurately modeling their fitness landscape. Given the limited availability of functional annotations from wet-lab experiments, previous methods have primarily relied on…

Machine Learning · Computer Science 2024-12-03 Zuobai Zhang , Pascal Notin , Yining Huang , Aurélie Lozano , Vijil Chenthamarakshan , Debora Marks , Payel Das , Jian Tang

AlphaFold2 (AF2) has transformed protein structure prediction by harnessing co-evolutionary constraints embedded in multiple sequence alignments (MSAs). MSAs not only encode static structural information, but also hold critical details…

Biomolecules · Quantitative Biology 2025-03-04 Enming Xing , Junjie Zhang , Shen Wang , Xiaolin Cheng

De novo molecular design has facilitated the exploration of large chemical space to accelerate drug discovery. Structure-based de novo method can overcome the data scarcity of active ligands by incorporating drug-target interaction into…

Biomolecules · Quantitative Biology 2022-09-16 Yaqin Li , Lingli Li , Yongjin Xu , Yi Yu