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We present a model, based on symmetry and geometry, for proteins. Using elementary ideas from mathematics and physics, we derive the geometries of discrete helices and sheets. We postulate a compatible solvent-mediated emergent pairwise…

Soft Condensed Matter · Physics 2023-06-21 Jayanth R. Banavar , Achille Giacometti , Trinh X. Hoang , Amos Maritan , Tatjana Škrbić

Probabilistic generative deep learning for molecular design involves the discovery and design of new molecules and analysis of their structure, properties and activities by probabilistic generative models using the deep learning approach.…

Machine Learning · Computer Science 2019-02-15 Daniel T. Chang

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

Proteins are macromolecules that perform essential functions in all living organisms. Designing novel proteins with specific structures and desired functions has been a long-standing challenge in the field of bioengineering. Existing…

Biomolecules · Quantitative Biology 2023-03-03 Chence Shi , Chuanrui Wang , Jiarui Lu , Bozitao Zhong , Jian Tang

While DeepMind has tentatively solved protein folding, its inverse problem -- protein design which predicts protein sequences from their 3D structures -- still faces significant challenges. Particularly, the lack of large-scale standardized…

Quantitative Methods · Quantitative Biology 2022-02-15 Zhangyang Gao , Cheng Tan , Stan Z. Li

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

Accurately modeling and designing protein complex structures is a central problem in computational structural biology, with broad implications for understanding cellular function and developing therapeutics. This thesis investigates two…

Machine Learning · Computer Science 2026-05-13 Ziwei Xie

Representation learning on graphs, also called graph embedding, has demonstrated its significant impact on a series of machine learning applications such as classification, prediction and recommendation. However, existing work has largely…

Machine Learning · Computer Science 2022-06-28 Yifan Hou , Hongzhi Chen , Changji Li , James Cheng , Ming-Chang Yang

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

Protein design has the potential to revolutionize biotechnology and medicine. While most efforts have focused on proteins with well-defined structures, increased recognition of the functional significance of intrinsically disordered…

Biomolecules · Quantitative Biology 2025-09-17 Giulio Tesei , Francesco Pesce , Kresten Lindorff-Larsen

We propose a novel probabilistic dimensionality reduction framework that can naturally integrate the generative model and the locality information of data. Based on this framework, we present a new model, which is able to learn a smooth…

Machine Learning · Statistics 2016-10-18 Li Wang

Proteins are fundamental to biology, executing diverse functions through complex physicochemical interactions, and they hold transformative potential across medicine, materials science, and environmental applications. Protein Language…

Biomolecules · Quantitative Biology 2025-06-11 Logan Hallee , Nikolaos Rafailidis , David B. Bichara , Jason P. Gleghorn

Proteins adopt multiple structural conformations to perform their diverse biological functions, and understanding these conformations is crucial for advancing drug discovery. Traditional physics-based simulation methods often struggle with…

Biomolecules · Quantitative Biology 2025-03-14 Jiarui Lu , Xiaoyin Chen , Stephen Zhewen Lu , Chence Shi , Hongyu Guo , Yoshua Bengio , Jian Tang

Efficient design and discovery of target-driven molecules is a critical step in facilitating lead optimization in drug discovery. Current approaches to develop molecules for a target protein are intuition-driven, hampered by slow iterative…

Machine Learning · Computer Science 2022-05-24 Andrew D. McNaughton , Mridula S. Bontha , Carter R. Knutson , Jenna A. Pope , Neeraj Kumar

Predicting the binding structure of a small molecule ligand to a protein -- a task known as molecular docking -- is critical to drug design. Recent deep learning methods that treat docking as a regression problem have decreased runtime…

Biomolecules · Quantitative Biology 2023-02-14 Gabriele Corso , Hannes Stärk , Bowen Jing , Regina Barzilay , Tommi Jaakkola

Representation learning is an important step in the machine learning pipeline. Given the current biological sequencing data volume, learning an explicit representation is prohibitive due to the dimensionality of the resulting feature…

Machine Learning · Computer Science 2023-04-04 Sarwan Ali , Usama Sardar , Murray Patterson , Imdad Ullah Khan

Representation learning and \emph{de novo} generation of proteins are pivotal computational biology tasks. Whilst natural language processing (NLP) techniques have proven highly effective for protein sequence modelling, structure modelling…

Quantitative Methods · Quantitative Biology 2025-01-08 Benoit Gaujac , Jérémie Donà , Liviu Copoiu , Timothy Atkinson , Thomas Pierrot , Thomas D. Barrett

The goal of protein representation learning is to extract knowledge from protein databases that can be applied to various protein-related downstream tasks. Although protein sequence, structure, and function are the three key modalities for…

Biomolecules · Quantitative Biology 2024-05-14 Eunji Ko , Seul Lee , Minseon Kim , Dongki Kim

The accurate prediction of protein-ligand binding affinity is important for drug discovery yet remains challenging for multi-domain proteins, where inter-domain dynamics and flexible linkers govern molecular recognition. Current geometric…

Quantitative Methods · Quantitative Biology 2026-01-27 Shuo Zhang , Jian K. Liu

Goal-directed molecular generation requires satisfying heterogeneous constraints such as protein--ligand compatibility and multi-objective drug-like properties, yet existing methods often optimize these constraints in isolation, failing to…

Machine Learning · Computer Science 2026-04-14 Yanting Li , Zhuoyang Jiang , Enyan Dai , Lei Wang , Wen-Cai Ye , Li Liu
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