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Artificial intelligence (AI)-driven methods can vastly improve the historically costly drug design process, with various generative models already in widespread use. Generative models for de novo drug design, in particular, focus on the…

Biomolecules · Quantitative Biology 2024-06-27 Xiangru Tang , Howard Dai , Elizabeth Knight , Fang Wu , Yunyang Li , Tianxiao Li , Mark Gerstein

Generative models emerge as promising candidates for novel sequence-data driven approaches to protein design, and for the extraction of structural and functional information about proteins deeply hidden in rapidly growing sequence…

Biomolecules · Quantitative Biology 2021-11-10 Jeanne Trinquier , Guido Uguzzoni , Andrea Pagnani , Francesco Zamponi , Martin Weigt

The advent of deep learning has introduced efficient approaches for de novo protein sequence design, significantly improving success rates and reducing development costs compared to computational or experimental methods. However, existing…

Artificial Intelligence · Computer Science 2024-07-11 Yutong Hu , Yang Tan , Andi Han , Lirong Zheng , Liang Hong , Bingxin Zhou

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

We propose generative neural network methods to generate DNA sequences and tune them to have desired properties. We present three approaches: creating synthetic DNA sequences using a generative adversarial network; a DNA-based variant of…

Machine Learning · Computer Science 2017-12-19 Nathan Killoran , Leo J. Lee , Andrew Delong , David Duvenaud , Brendan J. Frey

Designing protein sequences with specific biological functions and structural stability is crucial in biology and chemistry. Generative models already demonstrated their capabilities for reliable protein design. However, previous models are…

Machine Learning · Computer Science 2024-02-28 Lin Zongying , Li Hao , Lv Liuzhenghao , Lin Bin , Zhang Junwu , Chen Calvin Yu-Chian , Yuan Li , Tian Yonghong

Adeno-associated viral (AAV) vectors are widely used delivery platforms in gene therapy, and the design of improved capsids is key to expanding their therapeutic potential. A central challenge in AAV bioengineering, as in protein design…

Generating molecules that bind to specific proteins is an important but challenging task in drug discovery. Previous works usually generate atoms in an auto-regressive way, where element types and 3D coordinates of atoms are generated one…

Biomolecules · Quantitative Biology 2024-07-16 Haitao Lin , Yufei Huang , Odin Zhang , Siqi Ma , Meng Liu , Xuanjing Li , Lirong Wu , Jishui Wang , Tingjun Hou , Stan Z. Li

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

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

Analyzing the structure of proteins is a key part of understanding their functions and thus their role in biology at the molecular level. In addition, design new proteins in a methodical way is a major engineering challenge. In this work,…

Computer Vision and Pattern Recognition · Computer Science 2021-06-23 Hao Huang , Boulbaba Ben Amor , Xichan Lin , Fan Zhu , Yi Fang

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

Proteins are macromolecules responsible for essential functions in almost all living organisms. Designing reasonable proteins with desired functions is crucial. A protein's sequence and structure are strongly correlated and they together…

Machine Learning · Computer Science 2024-01-10 Zhenqiao Song , Yunlong Zhao , Wenxian Shi , Yang Yang , Lei Li

Proteins are dynamic, adopting ensembles of conformations. The nature of this conformational heterogenity is imprinted in the raw electron density measurements obtained from X-ray crystallography experiments. Fitting an ensemble of protein…

Quantitative Methods · Quantitative Biology 2024-12-19 Sai Advaith Maddipatla , Nadav Bojan Sellam , Sanketh Vedula , Ailie Marx , Alex Bronstein

Proteins are essential components of all living organisms and play a critical role in cellular survival. They have a broad range of applications, from clinical treatments to material engineering. This versatility has spurred the development…

Applications · Statistics 2025-03-28 Chenyu Ren , Daihai He , Jian Huang

SE(3)-based generative models have shown great promise in protein geometry modeling and effective structure design. However, the field currently lacks a modularized benchmark to enable comprehensive investigation and fair comparison of…

Machine Learning · Computer Science 2025-07-29 Lang Yu , Zhangyang Gao , Cheng Tan , Qin Chen , Jie Zhou , Liang He

Protein structure prediction and folding are fundamental to understanding biology, with recent deep learning advances reshaping the field. Diffusion-based generative models have revolutionized protein design, enabling the creation of novel…

Machine Learning · Computer Science 2025-10-01 Yogesh Verma , Markus Heinonen , Vikas Garg

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

We develop ProxelGen, a protein structure generative model that operates on 3D densities as opposed to the prevailing 3D point cloud representations. Representing proteins as voxelized densities, or proxels, enables new tasks and…

Biomolecules · Quantitative Biology 2025-06-25 Felix Faltings , Hannes Stark , Regina Barzilay , Tommi Jaakkola

Structure-based drug design (SBDD) aims to design small-molecule ligands that bind with high affinity and specificity to pre-determined protein targets. Generative SBDD methods leverage structural data of drugs in complex with their protein…