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Protein complex formation is a central problem in biology, being involved in most of the cell's processes, and essential for applications, e.g. drug design or protein engineering. We tackle rigid body protein-protein docking, i.e.,…

Artificial Intelligence · Computer Science 2022-03-16 Octavian-Eugen Ganea , Xinyuan Huang , Charlotte Bunne , Yatao Bian , Regina Barzilay , Tommi Jaakkola , Andreas Krause

The generation of small molecule candidate (ligand) binding poses in its target protein pocket is important for computer-aided drug discovery. Typical rigid-body docking methods ignore the pocket flexibility of protein, while the more…

Neural and Evolutionary Computing · Computer Science 2023-08-03 Jonathan P. Mailoa , Zhaofeng Ye , Jiezhong Qiu , Chang-Yu Hsieh , Shengyu Zhang

Generative deep learning techniques have demonstrated an impressive capacity for tackling biomolecular design problems in recent years. Despite their high performance, however, they still suffer from a lack of interpretability and rigorous…

Machine Learning · Computer Science 2026-04-06 Jyler Menard , R. A. Mansbach

The conformational landscape of proteins is crucial to understanding their functionality in complex biological processes. Traditional physics-based computational methods, such as molecular dynamics (MD) simulations, suffer from rare event…

Biomolecules · Quantitative Biology 2024-09-25 Yan Wang , Lihao Wang , Yuning Shen , Yiqun Wang , Huizhuo Yuan , Yue Wu , Quanquan Gu

The discovery of novel inhibitor molecules for emerging drug-target proteins is widely acknowledged as a challenging inverse design problem: Exhaustive exploration of the vast chemical search space is impractical, especially when the target…

The design of novel protein structures remains a challenge in protein engineering for applications across biomedicine and chemistry. In this line of work, a diffusion model over rigid bodies in 3D (referred to as frames) has shown success…

Machine Learning · Computer Science 2023-05-24 Jason Yim , Brian L. Trippe , Valentin De Bortoli , Emile Mathieu , Arnaud Doucet , Regina Barzilay , Tommi Jaakkola

Predicting the binding sites of target proteins plays a fundamental role in drug discovery. Most existing deep-learning methods consider a protein as a 3D image by spatially clustering its atoms into voxels and then feed the voxelized…

Biomolecules · Quantitative Biology 2024-07-24 Yang Zhang , Zhewei Wei , Ye Yuan , Chongxuan Li , Wenbing Huang

The computational prediction and design of peptide binders targeting specific linear epitopes is crucial in biological and biomedical research, yet it remains challenging due to their highly dynamic nature and the scarcity of experimentally…

Biomolecules · Quantitative Biology 2024-10-23 Haowen Zhao , Francesco A. Aprile , Barbara Bravi

Recent advancements in protein design have leveraged diffusion models to generate structural scaffolds, followed by a process known as protein inverse folding, which involves sequence inference on these scaffolds. However, these…

Biomolecules · Quantitative Biology 2025-02-27 Xingyi Zhang , Kun Xie , Ningqiao Huang , Wei Liu , Peilin Zhao , Sibo Wang , Kangfei Zhao , Biaobin Jiang

The lateral diffusion and trapping of protein receptors within the postsynaptic membrane of a neuron plays a key role in determining the strength of synaptic connections and their regulation during learning and memory. In this paper we…

Statistical Mechanics · Physics 2023-07-19 Paul C Bressloff

Understanding how proteins structurally interact is crucial to modern biology, with applications in drug discovery and protein design. Recent machine learning methods have formulated protein-small molecule docking as a generative problem…

Understanding and predicting the diverse conformational states of molecules is crucial for advancing fields such as chemistry, material science, and drug development. Despite significant progress in generative models, accurately generating…

Machine Learning · Computer Science 2025-01-14 Zhejun Zhang , Yuanping Chen , Shibing Chu

Epitopes are short antigenic peptide sequences which are recognized by antibodies or immune cell receptors. These are central to the development of immunotherapies, vaccines, and diagnostics. However, the rational design of synthetic…

Molecular conformation generation plays key roles in computational drug design. Recently developed deep learning methods, particularly diffusion models have reached competitive performance over traditional cheminformatical approaches.…

Machine Learning · Computer Science 2025-01-10 Yixuan Yang , Xingyu Fang , Zhaowen Cheng , Pengju Yan , Xiaolin Li

The protein-protein interactions (PPIs) are crucial for understanding the majority of cellular processes. PPIs play important role in gene transcription regulation, cellular signaling, molecular basis of immune response and more. Moreover,…

Biomolecules · Quantitative Biology 2016-05-31 Maciej Pawel Ciemny , Mateusz Kurcinski , Andrzej Kolinski , Sebastian Kmiecik

We consider the conditional generation of 3D drug-like molecules with \textit{explicit control} over molecular properties such as drug-like properties (e.g., Quantitative Estimate of Druglikeness or Synthetic Accessibility score) and…

Machine Learning · Computer Science 2024-12-20 Haoran Liu , Youzhi Luo , Tianxiao Li , James Caverlee , Martin Renqiang Min

In recent years, there has been an explosion of research on the application of deep learning to the prediction of various peptide properties, due to the significant development and market potential of peptides. Molecular dynamics has…

Biomolecules · Quantitative Biology 2023-07-19 Zihan Liu , Jiaqi Wang , Yun Luo , Shuang Zhao , Wenbin Li , Stan Z. Li

Antibodies offer great potential for the treatment of various diseases. However, the discovery of therapeutic antibodies through traditional wet lab methods is expensive and time-consuming. The use of generative models in designing…

Molecule generation, especially generating 3D molecular geometries from scratch (i.e., 3D \textit{de novo} generation), has become a fundamental task in drug designs. Existing diffusion-based 3D molecule generation methods could suffer from…

Machine Learning · Computer Science 2022-09-14 Lei Huang , Hengtong Zhang , Tingyang Xu , Ka-Chun Wong

Structure-based drug design, i.e., finding molecules with high affinities to the target protein pocket, is one of the most critical tasks in drug discovery. Traditional solutions, like virtual screening, require exhaustively searching on a…

Biomolecules · Quantitative Biology 2023-02-16 Shuqi Lu , Lin Yao , Xi Chen , Hang Zheng , Di He , Guolin Ke