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Topological data analysis (TDA) has had enormous success in science and engineering in the past decade. Persistent topological Laplacians (PTLs) overcome some limitations of persistent homology, a key technique in TDA, and provide…

Algebraic Topology · Mathematics 2023-12-05 Benjamin Jones , Guowei Wei

Accurate prediction of protein-ligand binding affinity remains a central challenge in structure-based drug discovery. The effectiveness of machine learning models critically depends on the quality of molecular descriptors, for which…

Biomolecules · Quantitative Biology 2026-03-24 Jian Liu , Hongsong Feng

Recent advances in topology-based modeling have accelerated progress in physical modeling and molecular studies, including applications to protein-ligand binding affinity. In this work, we introduce the Persistent Laplacian Decision Tree…

Biomolecules · Quantitative Biology 2024-12-25 Xingjian Xu , Jiahui Chen , Chunmei Wang

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

Accurate prediction of protein-ligand binding affinity is critical for drug discovery. While recent deep learning approaches have demonstrated promising results, they often rely solely on structural features of proteins and ligands,…

Machine Learning · Computer Science 2026-01-23 Han Liu , Keyan Ding , Peilin Chen , Yinwei Wei , Liqiang Nie , Dapeng Wu , Shiqi Wang

Predicting accurate protein-ligand binding affinity is important in drug discovery but remains a challenge even with computationally expensive biophysics-based energy scoring methods and state-of-the-art deep learning approaches. Despite…

Recently, topological data analysis has become a trending topic in data science and engineering. However, the key technique of topological data analysis, i.e., persistent homology, is defined on point cloud data, which does not work…

Differential Geometry · Mathematics 2024-11-08 Zhe Su , Yiying Tong , Guo-Wei Wei

Protein (receptor)--ligand interaction prediction is a critical component in computer-aided drug design, significantly influencing molecular docking and virtual screening processes. Despite the development of numerous scoring functions in…

Biomolecules · Quantitative Biology 2024-01-22 Haoyu Lin , Shiwei Wang , Jintao Zhu , Yibo Li , Jianfeng Pei , Luhua Lai

In structure-based drug design, accurately estimating the binding affinity between a candidate ligand and its protein receptor is a central challenge. Recent advances in artificial intelligence, particularly deep learning, have demonstrated…

Biomolecules · Quantitative Biology 2025-09-18 Md Masud Rana , Farjana Tasnim Mukta , Duc D. Nguyen

Protein-ligand binding is the process by which a small molecule (drug or inhibitor) attaches to a target protein. Binding affinity, which characterizes the strength of biomolecular interactions, is essential for tackling diverse challenges…

Predicting protein-ligand binding affinity remains intractable for multi-domain proteins, where inter-domain dynamics govern molecular recognition. Existing geometric deep learning methods typically treat proteins as monolithic static…

Machine Learning · Computer Science 2026-05-20 Shuo Zhang , Rongqi Hong , Huifeng Zhang , Jian K. Liu

Modeling the interaction between proteins and ligands and accurately predicting their binding structures is a critical yet challenging task in drug discovery. Recent advancements in deep learning have shown promise in addressing this…

Machine Learning · Computer Science 2024-01-10 Qizhi Pei , Kaiyuan Gao , Lijun Wu , Jinhua Zhu , Yingce Xia , Shufang Xie , Tao Qin , Kun He , Tie-Yan Liu , Rui Yan

Structure based ligand discovery is one of the most successful approaches for augmenting the drug discovery process. Currently, there is a notable shift towards machine learning (ML) methodologies to aid such procedures. Deep learning has…

Machine Learning · Statistics 2018-06-12 Marta M. Stepniewska-Dziubinska , Piotr Zielenkiewicz , Pawel Siedlecki

Prediction of protein-ligand interactions (PLI) plays a crucial role in drug discovery as it guides the identification and optimization of molecules that effectively bind to target proteins. Despite remarkable advances in deep…

Biomolecules · Quantitative Biology 2023-07-18 Seokhyun Moon , Sang-Yeon Hwang , Jaechang Lim , Woo Youn Kim

Understanding how protein mutations affect protein-nucleic acid binding is critical for unraveling disease mechanisms and advancing therapies. Current experimental approaches are laborious, and computational methods remain limited in…

Quantitative Methods · Quantitative Biology 2025-05-30 Xiang Liu , Junjie Wee , Guo-Wei Wei

Accurate prediction of protein-ligand binding affinities is an essential challenge in structure-based drug design. Despite recent advances in data-driven methods for affinity prediction, their accuracy is still limited, partially because…

Biomolecules · Quantitative Biology 2024-09-04 Yaosen Min , Ye Wei , Peizhuo Wang , Xiaoting Wang , Han Li , Nian Wu , Stefan Bauer , Shuxin Zheng , Yu Shi , Yingheng Wang , Ji Wu , Dan Zhao , Jianyang Zeng

Binding affinity optimization is crucial in early-stage drug discovery. While numerous machine learning methods exist for predicting ligand potency, their comparative efficacy remains unclear. This study evaluates the performance of…

Biomolecules · Quantitative Biology 2024-07-30 Nikolai Schapin , Carles Navarro , Albert Bou , Gianni De Fabritiis

Genetic mutations frequently disrupt protein structure, stability, and solubility, acting as primary drivers for a wide spectrum of diseases. Despite the critical importance of these molecular alterations, existing computational models…

Spectral Theory · Mathematics 2026-01-21 Yiming Ren , Junjie Wee , Xi Chen , Grace Qian , Guo-Wei Wei

The protein-ligand binding affinity (PLA) prediction goal is to predict whether or not the ligand could bind to a protein sequence. Recently, in PLA prediction, deep learning has received much attention. Two steps are involved in deep…

Quantitative Methods · Quantitative Biology 2024-05-21 Karim Abbasi , Parvin Razzaghi , Amin Ghareyazi , Hamid R. Rabiee

Persistent topological Laplacians constitute a new class of tools in topological data analysis (TDA). They are motivated by the necessity to address challenges encountered in persistent homology when handling complex data. These Laplacians…

Algebraic Topology · Mathematics 2024-12-12 Xiaoqi Wei , Guo-Wei Wei
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