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Antibodies are crucial proteins produced by the immune system in response to foreign substances or antigens. The specificity of an antibody is determined by its complementarity-determining regions (CDRs), which are located in the variable…

Biomolecules · Quantitative Biology 2024-01-11 Cheng Tan , Zhangyang Gao , Lirong Wu , Jun Xia , Jiangbin Zheng , Xihong Yang , Yue Liu , Bozhen Hu , Stan Z. Li

Multispecific antibodies offer transformative therapeutic potential by engaging multiple epitopes simultaneously, yet their efficacy is an emergent property governed by complex molecular architectures. Rational design is often bottlenecked…

Kernel classifiers and regressors designed for structured data, such as sequences, trees and graphs, have significantly advanced a number of interdisciplinary areas such as computational biology and drug design. Typically, kernels are…

Machine Learning · Computer Science 2020-01-14 Hanjun Dai , Bo Dai , Le Song

Recent advances in generative models, particularly diffusion and auto-regressive models, have revolutionized fields like computer vision and natural language processing. However, their application to structure-based drug design (SBDD)…

Machine Learning · Computer Science 2025-07-29 Yi He , Ailun Wang , Zhi Wang , Yu Liu , Xingyuan Xu , Wen Yan

Protein engineering seeks to identify protein sequences with optimized properties. When guided by machine learning, protein sequence generation methods can draw on prior knowledge and experimental efforts to improve this process. In this…

Quantitative Methods · Quantitative Biology 2021-05-28 Zachary Wu , Kadina E. Johnston , Frances H. Arnold , Kevin K. Yang

Antibodies are essential proteins responsible for immune responses in organisms, capable of specifically recognizing antigen molecules of pathogens. Recent advances in generative models have significantly enhanced rational antibody design.…

Artificial Intelligence · Computer Science 2025-11-10 Zichen Wang , Yaokun Ji , Jianing Tian , Shuangjia Zheng

This paper introduces a novel non-parametric deep model for estimating time-to-event (survival analysis) in presence of censored data and competing risks. The model is designed based on the sequence-to-sequence (Seq2Seq) architecture,…

Deep learning has recently been applied to various research areas of design optimization. This study presents the need and effectiveness of adopting deep learning for generative design (or design exploration) research area. This work…

Machine Learning · Computer Science 2020-05-27 Sangeun Oh , Yongsu Jung , Seongsin Kim , Ikjin Lee , Namwoo Kang

Deep autoregressive sequence-to-sequence models have demonstrated impressive performance across a wide variety of tasks in recent years. While common architecture classes such as recurrent, convolutional, and self-attention networks make…

Machine Learning · Computer Science 2018-11-09 Mitchell Stern , Noam Shazeer , Jakob Uszkoreit

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

Protein generative models have shown remarkable promise in protein design, yet their success rates remain constrained by reliance on curated sequence-structure datasets and by misalignment between supervised objectives and real design…

Machine Learning · Computer Science 2026-03-03 Ziwen Wang , Jiajun Fan , Ruihan Guo , Thao Nguyen , Heng Ji , Ge Liu

Biological machine learning is often bottlenecked by a lack of scaled data. One promising route to relieving data bottlenecks is through high throughput screens, which can experimentally test the activity of $10^6-10^{12}$ protein sequences…

Machine Learning · Statistics 2025-10-21 Eli N. Weinstein , Andrei Slabodkin , Mattia G. Gollub , Elizabeth B. Wood

Deep generative models have achieved tremendous success in structure-based drug design in recent years, especially for generating 3D ligand molecules that bind to specific protein pocket. Notably, diffusion models have transformed ligand…

Machine Learning · Computer Science 2024-12-03 Daiheng Zhang , Chengyue Gong , Qiang Liu

AlphaFold can be used for both single-chain and multi-chain protein structure prediction, while the latter becomes extremely challenging as the number of chains increases. In this work, by taking each chain as a node and assembly actions as…

Computational Engineering, Finance, and Science · Computer Science 2024-05-08 Ziqi Gao , Tao Feng , Jiaxuan You , Chenyi Zi , Yan Zhou , Chen Zhang , Jia Li

Abstract Recent advances in immunology and synthetic biology have accelerated the development of deep generative methods for DNA sequence design. Two dominant approaches in this field are AutoRegressive (AR) models and Diffusion Models…

Genomics · Quantitative Biology 2024-10-30 Zehui Li , Yuhao Ni , Guoxuan Xia , William Beardall , Akashaditya Das , Guy-Bart Stan , Yiren Zhao

Simultaneously optimizing molecules against multiple therapeutic targets remains a profound challenge in drug discovery, particularly due to sparse rewards and conflicting design constraints. We propose a structured active learning (AL)…

Machine Learning · Computer Science 2025-06-24 Júlia Vilalta-Mor , Alexis Molina , Laura Ortega Varga , Isaac Filella-Merce , Victor Guallar

The functions of proteins and RNAs are determined by a myriad of interactions between their constituent residues, but most quantitative models of how molecular phenotype depends on genotype must approximate this by simple additive effects.…

Quantitative Methods · Quantitative Biology 2017-12-19 Adam J. Riesselman , John B. Ingraham , Debora S. Marks

Graph generation poses a significant challenge as it involves predicting a complete graph with multiple nodes and edges based on simply a given label. This task also carries fundamental importance to numerous real-world applications,…

Machine Learning · Computer Science 2024-02-21 Xiandong Zou , Xiangyu Zhao , Pietro Liò , Yiren Zhao

Geometric Graph Neural Networks (GNNs) and Transformers have become state-of-the-art for learning from 3D protein structures. However, their reliance on message passing prevents them from capturing the hierarchical interactions that govern…

Machine Learning · Computer Science 2025-12-09 Chang Liu , Vivian Li , Linus Leong , Vladimir Radenkovic , Pietro Liò , Chaitanya K. Joshi

Generative Design (GD) has evolved as a transformative design approach, employing advanced algorithms and AI to create diverse and innovative solutions beyond traditional constraints. Despite its success, GD faces significant challenges…

Computer Vision and Pattern Recognition · Computer Science 2024-03-20 Jihoon Kim , Yongmin Kwon , Namwoo Kang