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Protein inverse folding is a fundamental problem in bioinformatics, aiming to recover the amino acid sequences from a given protein backbone structure. Despite the success of existing methods, they struggle to fully capture the intricate…

Machine Learning · Computer Science 2024-12-13 Chenglin Wang , Yucheng Zhou , Zijie Zhai , Jianbing Shen , Kai Zhang

AlphaFold 3 (AF3) is a powerful biomolecular structure-predicting tool based on the latest deep learning algorithms and revolutionized AI model architectures. A few of papers have already investigated its accuracy in predicting different…

Biomolecules · Quantitative Biology 2025-11-19 Yiyang Xu , Ziyou Shen , Yanqing Lv , Shutong Tan , Chun Sun , Juan Zhang

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

Recent developments in deep learning-based methods demonstrated its potential to predict the 3D protein structures using inputs such as protein sequences, Cryo-Electron microscopy (Cryo-EM) images of proteins, etc. However, these methods…

Computer Vision and Pattern Recognition · Computer Science 2022-11-29 Jaydeep Rade , Soumik Sarkar , Anwesha Sarkar , Adarsh Krishnamurthy

Protein loop modeling is the most challenging yet highly non-trivial task in protein structure prediction. Despite recent progress, existing methods including knowledge-based, ab initio, hybrid and deep learning (DL) methods fall…

Biomolecules · Quantitative Biology 2023-06-23 Tianyue Wang , Xujun Zhang , Odin Zhang , Peichen Pan , Guangyong Chen , Yu Kang , Chang-Yu Hsieh , Tingjun Hou

While deep generative models show promise for learning inverse protein folding directly from data, the lack of publicly available structure-sequence pairings limits their generalization. Previous improvements and data augmentation efforts…

Artificial Intelligence · Computer Science 2024-07-23 Jiangbin Zheng , Stan Z. Li

The binding complexes formed by proteins and small molecule ligands are ubiquitous and critical to life. Despite recent advancements in protein structure prediction, existing algorithms are so far unable to systematically predict the…

Quantitative Methods · Quantitative Biology 2023-04-21 Zhuoran Qiao , Weili Nie , Arash Vahdat , Thomas F. Miller , Anima Anandkumar

The design of protein sequences with desired functionalities is a fundamental task in protein engineering. Deep generative methods, such as autoregressive models and diffusion models, have greatly accelerated the discovery of novel protein…

Machine Learning · Computer Science 2025-04-16 Zitai Kong , Yiheng Zhu , Yinlong Xu , Hanjing Zhou , Mingzhe Yin , Jialu Wu , Hongxia Xu , Chang-Yu Hsieh , Tingjun Hou , Jian Wu

Proteins are the basic building blocks of life. They usually perform functions by folding to a particular structure. Understanding the folding process could help the researchers to understand the functions of proteins and could also help to…

Computational Engineering, Finance, and Science · Computer Science 2015-10-21 Jianzhu Ma

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

Structure-based drug design (SBDD) aims to generate 3D ligand molecules that bind to specific protein targets. Existing 3D deep generative models including diffusion models have shown great promise for SBDD. However, it is complex to…

Biomolecules · Quantitative Biology 2024-03-01 Zhilin Huang , Ling Yang , Zaixi Zhang , Xiangxin Zhou , Yu Bao , Xiawu Zheng , Yuwei Yang , Yu Wang , Wenming Yang

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

The intricate three-dimensional geometries of protein tertiary structures underlie protein function and emerge through a folding process from one-dimensional chains of amino acids. The exact spatial sequence and configuration of amino…

Biomolecules · Quantitative Biology 2021-02-24 Nora Molkenthin , Steffen Mühle , Antonia S J S Mey , Marc Timme

Protein sequence generation for engineering requires samples that are biophysically plausible and, when targeting a family/domain, remain recognizable members while exploring within-family diversity. Current discrete generative models…

Computational Engineering, Finance, and Science · Computer Science 2026-05-25 Langzhang Liang , Ming Yang , Yi Feng , Junfan Li , Shirui Pan , Yinghui Xu , Tianlei Ying , Yizhen Zheng , Zenglin Xu

Structure-based drug design (SBDD), which aims to generate molecules that can bind tightly to the target protein, is an essential problem in drug discovery, and previous approaches have achieved initial success. However, most existing…

Machine Learning · Computer Science 2024-04-04 Xinze Li , Penglei Wang , Tianfan Fu , Wenhao Gao , Chengtao Li , Leilei Shi , Junhong Liu

We introduce and explore an approach for constructing force fields for small molecules, which combines intuitive low body order empirical force field terms with the concepts of data driven statistical fits of recent machine learned…

Chemical Physics · Physics 2020-10-26 Alice Allen , Gábor Csányi , Geneviève Dusson , Christoph Ortner

Biological processes, functions, and properties are intricately linked to the ensemble of protein conformations, rather than being solely determined by a single stable conformation. In this study, we have developed P2DFlow, a generative…

Biological Physics · Physics 2025-03-05 Yaowei Jin , Qi Huang , Ziyang Song , Mingyue Zheng , Dan Teng , Qian Shi

Generating protein sequences that fold into a intended 3D structure is a fundamental step in de novo protein design. De facto methods utilize autoregressive generation, but this eschews higher order interactions that could be exploited to…

Biomolecules · Quantitative Biology 2023-12-06 John J. Yang , Jason Yim , Regina Barzilay , Tommi Jaakkola

Generative models of macromolecules carry abundant and impactful implications for industrial and biomedical efforts in protein engineering. However, existing methods are currently limited to modeling protein structures or sequences,…

Biomolecules · Quantitative Biology 2024-01-15 Alex Morehead , Jeffrey Ruffolo , Aadyot Bhatnagar , Ali Madani

Molecular structure generation is a fundamental problem that involves determining the 3D positions of molecules' constituents. It has crucial biological applications, such as molecular docking, protein folding, and molecular design. Recent…

Machine Learning · Computer Science 2025-08-27 Wenyin Zhou , Christopher Iliffe Sprague , Vsevolod Viliuga , Matteo Tadiello , Arne Elofsson , Hossein Azizpour