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Recent remarkable advancements in geometric deep generative models, coupled with accumulated structural data, enable structure-based drug design (SBDD) using only target protein information. However, existing models often struggle to…

Biomolecules · Quantitative Biology 2026-03-09 Joongwon Lee , Wonho Zhung , Jisu Seo , Woo Youn Kim

Diffusion generative models have emerged as a powerful framework for addressing problems in structural biology and structure-based drug design. These models operate directly on 3D molecular structures. Due to the unfavorable scaling of…

Biomolecules · Quantitative Biology 2024-05-10 Ian Dunn , David Ryan Koes

This paper investigates the application of the transformer architecture in protein folding, as exemplified by DeepMind's AlphaFold project, and its implications for the understanding of so-called large language models. The prevailing…

Computers and Society · Computer Science 2024-12-10 Fabian Offert , Paul Kim , Qiaoyu Cai

Designing novel proteins with desired functions is crucial in biology and chemistry. However, most existing work focus on protein sequence design, leaving protein sequence and structure co-design underexplored. In this paper, we propose…

Machine Learning · Computer Science 2023-10-05 Zhenqiao Song , Yunlong Zhao , Yufei Song , Wenxian Shi , Yang Yang , Lei Li

Multimodal protein language models (PLMs) integrate sequence and token-based structural information, serving as a powerful foundation for protein modeling, generation, and design. However, the reliance on tokenizing 3D structures into…

Machine Learning · Computer Science 2025-06-13 Cheng-Yen Hsieh , Xinyou Wang , Daiheng Zhang , Dongyu Xue , Fei Ye , Shujian Huang , Zaixiang Zheng , Quanquan Gu

Predicting drug-target interaction (DTI) is critical in the drug discovery process. Despite remarkable advances in recent DTI models through the integration of representations from diverse drug and target encoders, such models often…

Quantitative Methods · Quantitative Biology 2025-09-30 Zhaohan Meng , Zaiqiao Meng , Ke Yuan , Iadh Ounis

The linear sequence of amino acids determines protein structure and function. Protein design, known as the inverse of protein structure prediction, aims to obtain a novel protein sequence that will fold into the defined structure. Recent…

Biomolecules · Quantitative Biology 2023-02-22 Cheng Tan , Zhangyang Gao , Jun Xia , Bozhen Hu , Stan Z. Li

Motivation: The clinical efficacy of antibody therapeutics critically depends on high-affinity target engagement, yet laboratory affinity-maturation campaigns are slow and costly. In computational settings, most protein language models…

Computational Engineering, Finance, and Science · Computer Science 2025-12-22 Xinyan Zhao , Yi-Ching Tang , Rivaaj Monsia , Victor J. Cantu , Ashwin Kumar Ramesh , Xiaozhong Liu , Zhiqiang An , Xiaoqian Jiang , Yejin Kim

Proteins are complex biomolecules that perform a variety of crucial functions within living organisms. Designing and generating novel proteins can pave the way for many future synthetic biology applications, including drug discovery.…

In recent years, there has been a surge in the development of 3D structure-based pre-trained protein models, representing a significant advancement over pre-trained protein language models in various downstream tasks. However, most existing…

Machine Learning · Computer Science 2024-06-04 Jiale Zhao , Wanru Zhuang , Jia Song , Yaqi Li , Shuqi Lu

Designing compounds with desired properties is a key element of the drug discovery process. However, measuring progress in the field has been challenging due to the lack of realistic retrospective benchmarks, and the large cost of…

Biomolecules · Quantitative Biology 2023-06-16 Tobiasz Cieplinski , Tomasz Danel , Sabina Podlewska , Stanislaw Jastrzebski

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

Proteolysis-Targeting Chimeras (PROTACs) represent a novel class of small molecules which are designed to act as a bridge between an E3 ligase and a disease-relevant protein, thereby promoting its subsequent degradation. PROTACs are…

Machine Learning · Computer Science 2023-06-16 Rebecca M. Neeser , Mehmet Akdel , Daniel Kovtun , Luca Naef

Accurate protein structures are essential for understanding biological function, yet incorporating experimental data into protein generative models remains a major challenge. Most predictors of experimental observables are…

Machine Learning · Computer Science 2025-11-18 Nadav Bojan Sellam , Meital Bojan , Paul Schanda , Alex Bronstein

Computational protein design has a wide variety of applications. Despite its remarkable success, designing a protein for a given structure and function is still a challenging task. On the other hand, the number of solved protein structures…

Quantitative Methods · Quantitative Biology 2018-04-26 Jingxue Wang , Huali Cao , John Z. H. Zhang , Yifei Qi

While monomer protein structure prediction tools boast impressive accuracy, the prediction of protein complex structures remains a daunting challenge in the field. This challenge is particularly pronounced in scenarios involving complexes…

Biomolecules · Quantitative Biology 2024-05-20 Xiaomin Fang , Jie Gao , Jing Hu , Lihang Liu , Yang Xue , Xiaonan Zhang , Kunrui Zhu

Diffusion models offer a powerful means of capturing the manifold of realistic protein structures, enabling rapid design for protein engineering tasks. However, existing approaches observe critical failure modes when precise constraints are…

Biomolecules · Quantitative Biology 2026-03-27 Jacob K. Christopher , Austin Seamann , Jingyi Cui , Sagar Khare , Ferdinando Fioretto

Motivation: Protein interactions are fundamental building blocks of biochemical reaction systems underlying cellular functions. The complexity and functionality of such systems emerge not from the protein interactions themselves but from…

Molecular Networks · Quantitative Biology 2011-06-15 Johannes Köster , Eli Zamir , Sven Rahmann

Through evolution, nature has presented a set of remarkable protein materials, including elastins, silks, keratins and collagens with superior mechanical performances that play crucial roles in mechanobiology. However, going beyond natural…

Materials Science · Physics 2023-12-19 Bo Ni , David L. Kaplan , Markus J. Buehler

The de novo design of ligand-binding proteins with tailored functions is essential for advancing biotechnology and molecular medicine, yet existing AI approaches are limited by scarce protein-ligand complex data. To circumvent this data…

Machine Learning · Computer Science 2026-03-03 Zhenqiao Song , Ramith Hettiarachchi , Chuan Li , Jianwen Xie , Lei Li