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The arc of drug discovery entails a multiparameter optimization problem spanning vast length scales. They key parameters range from solubility (angstroms) to protein-ligand binding (nanometers) to in vivo toxicity (meters). Through feature…

In spite of decades of research, much remains to be discovered about folding: the detailed structure of the initial (unfolded) state, vestigial folding instructions remaining only in the unfolded state, the interaction of the molecule with…

Biological Physics · Physics 2018-11-26 Walter A. Simmons

Accurately predicting the binding conformation of small-molecule ligands to protein targets is a critical step in rational drug design. Although recent deep learning-based docking surpasses traditional methods in speed and accuracy, many…

Computer Vision and Pattern Recognition · Computer Science 2025-08-14 Liyan Jia , Chuan-Xian Ren , Hong Yan

Protein structure prediction is a critical and longstanding challenge in biology, garnering widespread interest due to its significance in understanding biological processes. A particular area of focus is the prediction of missing loops in…

The AlphaFold Protein Structure Database (AFDB) offers unparalleled structural coverage at near-experimental accuracy, positioning it as a valuable resource for data-driven protein design. However, its direct use in training deep models…

Machine Learning · Computer Science 2025-06-11 Cheng Tan , Zhenxiao Cao , Zhangyang Gao , Siyuan Li , Yufei Huang , Stan Z. Li

Efficient indexing and searching of high dimensional data has been an area of active research due to the growing exploitation of high dimensional data and the vulnerability of traditional search methods to the curse of dimensionality. This…

Information Retrieval · Computer Science 2015-05-13 Yu Zhong

Understanding the structure of a protein complex is crucial indetermining its function. However, retrieving accurate 3D structures from microscopy images is highly challenging, particularly as many imaging modalities are two-dimensional.…

Quantitative Methods · Quantitative Biology 2021-10-18 Benjamin J. Blundell , Christian Sieben , Suliana Manley , Ed Rosten , QueeLim Ch'ng , Susan Cox

Simulations of biological macromolecules play an important role in understanding the physical basis of a number of complex processes such as protein folding. Even with increasing computational power and evolution of specialized…

Distributed, Parallel, and Cluster Computing · Computer Science 2019-09-18 Hyungro Lee , Heng Ma , Matteo Turilli , Debsindhu Bhowmik , Shantenu Jha , Arvind Ramanathan

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 potential of deep learning has been recognized in the protein structure prediction community for some time, and became indisputable after CASP13. In CASP14, deep learning has boosted the field to unanticipated levels reaching…

Biomolecules · Quantitative Biology 2021-09-14 Elodie Laine , Stephan Eismann , Arne Elofsson , Sergei Grudinin

Structure-based drug design (SBDD) leverages the three-dimensional geometry of proteins to identify potential drug candidates. Traditional approaches, rooted in physicochemical modeling and domain expertise, are often resource-intensive.…

Quantitative Methods · Quantitative Biology 2024-11-19 Zaixi Zhang , Jiaxian Yan , Yining Huang , Qi Liu , Enhong Chen , Mengdi Wang , Marinka Zitnik

The detailed analysis of molecular structures and properties holds great potential for drug development discovery through machine learning. Developing an emergent property in the model to understand molecules would broaden the horizons for…

Protein-protein interactions (PPIs) are crucial in regulating numerous cellular functions, including signal transduction, transportation, and immune defense. As the accuracy of multi-chain protein complex structure prediction improves, the…

Biomolecules · Quantitative Biology 2024-02-07 Chenqing Hua , Connor Coley , Guy Wolf , Doina Precup , Shuangjia Zheng

Graph representation learning is a fast-growing field where one of the main objectives is to generate meaningful representations of graphs in lower-dimensional spaces. The learned embeddings have been successfully applied to perform various…

Machine Learning · Computer Science 2021-12-21 Md. Khaledur Rahman , Ariful Azad

Mining large-scale high-throughput tandem mass spectrometry data sets is a very important problem in mass spectrometry based protein identification. One of the fundamental problems in large scale mining of spectra is to design appropriate…

Quantitative Methods · Quantitative Biology 2007-05-23 Debojyoti Dutta , Ting Chen

Targeted protein degradation (TPD) induced by small molecules has emerged as a rapidly evolving modality in drug discovery, targeting proteins traditionally considered "undruggable". Proteolysis-targeting chimeras (PROTACs) and molecular…

Biomolecules · Quantitative Biology 2025-02-27 Fanglei Xue , Meihan Zhang , Shuqi Li , Xinyu Gao , James A. Wohlschlegel , Wenbing Huang , Yi Yang , Weixian Deng

De novo protein structure prediction from amino acid sequence is one of the most challenging problems in computational biology. As one of the extensively explored mathematical models for protein folding, Hydrophobic-Polar (HP) model enables…

Machine Learning · Computer Science 2018-12-06 Yanjun Li , Hengtong Kang , Ketian Ye , Shuyu Yin , Xiaolin Li

Proteins are sequences of amino acids that serve as the basic building blocks of living organisms. Despite rapidly growing databases documenting structural and functional information for various protein sequences, our understanding of…

Biomolecules · Quantitative Biology 2025-01-06 Weihang Dai

Recent advancements in machine learning techniques for protein folding motivate better results in its inverse problem -- protein design. In this work we introduce a new graph mimetic neural network, MimNet, and show that it is possible to…

Biomolecules · Quantitative Biology 2021-02-09 Moshe Eliasof , Tue Boesen , Eldad Haber , Chen Keasar , Eran Treister

The computation of distance measures between nodes in graphs is inefficient and does not scale to large graphs. We explore dense vector representations as an effective way to approximate the same information: we introduce a simple yet…

Computation and Language · Computer Science 2019-06-18 Andrey Kutuzov , Mohammad Dorgham , Oleksiy Oliynyk , Chris Biemann , Alexander Panchenko