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Physics-informed neural networks (PINNs) have emerged as a powerful tool for solving physical systems described by partial differential equations (PDEs). However, their accuracy in dynamical systems, particularly those involving sharp…

Computational Physics · Physics 2026-03-03 Wei Wang , Tang Paai Wong , Haihui Ruan , Somdatta Goswami

Traditional drug discovery relies on rounds of screening millions of candidate molecules with low success rates, making drug discovery time and resource intensive. To overcome this screening bottleneck, we introduce Latent-X, an all-atom…

To fully leverage the capabilities of diffusion models, we are often interested in optimizing downstream reward functions during inference. While numerous algorithms for reward-guided generation have been recently proposed due to their…

Machine Learning · Computer Science 2025-04-18 Masatoshi Uehara , Xingyu Su , Yulai Zhao , Xiner Li , Aviv Regev , Shuiwang Ji , Sergey Levine , Tommaso Biancalani

Peptides, short chains of amino acid residues, play a vital role in numerous biological processes by interacting with other target molecules, offering substantial potential in drug discovery. In this work, we present PepFlow, the first…

Biomolecules · Quantitative Biology 2024-06-04 Jiahan Li , Chaoran Cheng , Zuofan Wu , Ruihan Guo , Shitong Luo , Zhizhou Ren , Jian Peng , Jianzhu Ma

The recent breakthrough of AlphaFold3 in modeling complex biomolecular interactions, including those between proteins and ligands, nucleotides, or metal ions, creates new opportunities for protein design. In so-called inverse protein…

Biomolecules · Quantitative Biology 2025-07-22 Kai Yi , Kiarash Jamali , Sjors H. W. Scheres

While Retrieval-Augmented Generation (RAG) mitigates hallucination and knowledge staleness in Large Language Models (LLMs), existing frameworks often falter on complex, multi-hop queries that require synthesizing information from disparate…

Computation and Language · Computer Science 2025-10-28 Mohammad Aghajani Asl , Majid Asgari-Bidhendi , Behrooz Minaei-Bidgoli

Proteins perform critical processes in all living systems: converting solar energy into chemical energy, replicating DNA, as the basis of highly performant materials, sensing and much more. While an incredible range of functionality has…

Biomolecules · Quantitative Biology 2021-09-29 Leonardo V. Castorina , Rokas Petrenas , Kartic Subr , Christopher W. Wood

Recent studies have shown competitive performance in protein design that aims to find the amino acid sequence folding into the desired structure. However, most of them disregard the importance of predictive confidence, fail to cover the…

Biomolecules · Quantitative Biology 2023-05-31 Zhangyang Gao , Cheng Tan , Stan Z. Li

We apply a new approach to the reverse protein folding problem. Our method uses a minimization function in the design process which is different from the energy function used for folding. For a lattice model, we show that this new approach…

Condensed Matter · Physics 2009-10-28 J. M. Deutsch , Tanya Kurosky

Designing novel protein sequences for a desired 3D topological fold is a fundamental yet non-trivial task in protein engineering. Challenges exist due to the complex sequence--fold relationship, as well as the difficulties to capture the…

Machine Learning · Computer Science 2021-06-25 Yue Cao , Payel Das , Vijil Chenthamarakshan , Pin-Yu Chen , Igor Melnyk , Yang Shen

Peptide design plays a pivotal role in therapeutics, allowing brand new possibility to leverage target binding sites that are previously undruggable. Most existing methods are either inefficient or only concerned with the target-agnostic…

Biomolecules · Quantitative Biology 2024-10-31 Xiangzhe Kong , Yinjun Jia , Wenbing Huang , Yang Liu

Protein inverse folding aims to design an amino acid sequence that will fold into a given backbone structure, serving as a central task in protein design. Two main paradigms have been widely explored. Template-based methods exploit…

Machine Learning · Computer Science 2026-03-17 Yiran Zhu , Changxi Chi , Hongxin Xiang , Wenjie Du , Xiaoqi Wang , Jun Xia

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

Inverse Protein Folding (IPF) is a critical subtask in the field of protein design, aiming to engineer amino acid sequences capable of folding correctly into a specified three-dimensional (3D) conformation. Although substantial progress has…

Computation and Language · Computer Science 2025-05-20 Yanting Li , Jiyue Jiang , Zikang Wang , Ziqian Lin , Dongchen He , Yuheng Shan , Yanruisheng Shao , Jiayi Li , Xiangyu Shi , Jiuming Wang , Yanyu Chen , Yimin Fan , Han Li , Yu Li

Breakthroughs in high-accuracy protein structure prediction, such as AlphaFold, have established receptor-based molecule design as a critical driver for rapid early-phase drug discovery. However, most approaches still struggle to balance…

Biomolecules · Quantitative Biology 2025-06-18 Dong Xu , Zhangfan Yang , Ka-chun Wong , Zexuan Zhu , Jiangqiang Li , Junkai Ji

Composed Image Retrieval (CIR) presents a significant challenge as it requires jointly understanding a reference image and a modified textual instruction to find relevant target images. Some existing methods attempt to use a two-stage…

Computer Vision and Pattern Recognition · Computer Science 2025-12-15 Jun Li , Hongjian Dou , Zhenyu Zhang , Kai Li , Shaoguo Liu , Tingting Gao

Atomistic modeling of solid-solid battery interfaces is essential for understanding electro-chemo-mechanical coupling, but the complex interfacial chemistry and heterogeneous environments pose major challenges for quantum-accurate,…

Materials Science · Physics 2026-01-27 Xiaoqing Liu , Xinyu Yu , Yangshuai Wang , Zhe-Tao Sun , Zedong Luo , Kehan Zeng , Teng Zhao , Shou-Hang Bo , Zhenli Xu

How can we design protein sequences folding into the desired structures effectively and efficiently? AI methods for structure-based protein design have attracted increasing attention in recent years; however, few methods can simultaneously…

Artificial Intelligence · Computer Science 2023-04-14 Zhangyang Gao , Cheng Tan , Pablo Chacón , Stan Z. Li

Deep learning has transformed protein design, enabling accurate structure prediction, sequence optimization, and de novo protein generation. Advances in single-chain protein structure prediction via AlphaFold2, RoseTTAFold, ESMFold, and…

Machine Learning · Computer Science 2025-02-27 Gregory W. Kyro , Tianyin Qiu , Victor S. Batista

Inverse protein folding, the process of designing sequences that fold into a specific 3D structure, is crucial in bio-engineering and drug discovery. Traditional methods rely on experimentally resolved structures, but these cover only a…

Biomolecules · Quantitative Biology 2023-11-27 Igor Melnyk , Aurelie Lozano , Payel Das , Vijil Chenthamarakshan