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Predicting interactions between biomolecules, such as protein-protein complexes, remains a challenging problem. Despite the many advancements done so far, the performances of docking protocols are deeply dependent on their capability of…

Biomolecules · Quantitative Biology 2025-08-19 Greta Grassmann , Lorenzo Di Rienzo , Giancarlo Ruocco , Mattia Miotto , Edoardo Milanetti

The cornerstone of computational drug design is the calculation of binding affinity between two biological counterparts, especially a chemical compound, i.e., a ligand, and a protein. Predicting the strength of protein-ligand binding with…

Biomolecules · Quantitative Biology 2019-12-04 Yanjun Li , Mohammad A. Rezaei , Chenglong Li , Xiaolin Li , Dapeng Wu

Despite continuing hype about the role of AI in drug discovery, no "AI-discovered drugs" have so far received regulatory approval. Here we assess one of the latest AI based tools in this domain. The ability to rapidly predict protein-ligand…

Chemical Physics · Physics 2026-03-09 Shunzhou Wan , Xibei Zhang , Xiao Xue , Peter V. Coveney

Computational approaches to drug discovery can reduce the time and cost associated with experimental assays and enable the screening of novel chemotypes. Structure-based drug design methods rely on scoring functions to rank and predict…

Machine Learning · Statistics 2020-10-19 Matthew Ragoza , Joshua Hochuli , Elisa Idrobo , Jocelyn Sunseri , David Ryan Koes

Predicting how a drug-like molecule binds to a specific protein target is a core problem in drug discovery. An extremely fast computational binding method would enable key applications such as fast virtual screening or drug engineering.…

Biomolecules · Quantitative Biology 2022-06-07 Hannes Stärk , Octavian-Eugen Ganea , Lagnajit Pattanaik , Regina Barzilay , Tommi Jaakkola

We devise an approach for targeted molecular design, a problem of interest in computational drug discovery: given a target protein site, we wish to generate a chemical with both high binding affinity to the target and satisfactory…

Artificial Intelligence · Computer Science 2018-09-07 Tristan Aumentado-Armstrong

While deep learning has revolutionized computer-aided drug discovery, the AI community has predominantly focused on model innovation and placed less emphasis on establishing best benchmarking practices. We posit that without a sound model…

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

The structure of proteins is the basis for studying protein function and drug design. The emergence of AlphaFold 2 has greatly promoted the prediction of protein 3D structures, and it is of great significance to give an overall and accurate…

Biomolecules · Quantitative Biology 2024-07-02 Wenda Wang , Jiaqi Zhai , He Huang , Xinqi Gong

Understanding decision-making in clinical environments is of paramount importance if we are to bring the strengths of machine learning to ultimately improve patient outcomes. Several factors including the availability of public data, the…

Machine Learning · Computer Science 2022-03-15 Alex J. Chan , Ioana Bica , Alihan Huyuk , Daniel Jarrett , Mihaela van der Schaar

This paper presents the methods that have participated in the SHREC 2022 contest on protein-ligand binding site recognition. The prediction of protein-ligand binding regions is an active research domain in computational biophysics and…

Deep generative models have achieved tremendous success in designing novel drug molecules in recent years. A new thread of works have shown the great potential in advancing the specificity and success rate of in silico drug design by…

Machine Learning · Computer Science 2025-07-14 Xingang Peng , Shitong Luo , Jiaqi Guan , Qi Xie , Jian Peng , Jianzhu Ma

Effective communication, specifically through documentation, is the beating heart of collaboration among contributors in software development. Recent advancements in language models (LMs) have enabled the introduction of a new type of actor…

Software Engineering · Computer Science 2024-05-17 Bibek Poudel , Adam Cook , Sekou Traore , Shelah Ameli

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

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

Molecular docking is critical to structure-based virtual screening, yet the throughput of such workflows is limited by the expensive optimization of scoring functions involved in most docking algorithms. We explore how machine learning can…

Biomolecules · Quantitative Biology 2024-09-04 Bowen Jing , Tommi Jaakkola , Bonnie Berger

Current molecular understanding approaches predominantly focus on the descriptive aspect of human perception, providing broad, topic-level insights. However, the referential aspect -- linking molecular concepts to specific structural…

Artificial Intelligence · Computer Science 2025-05-02 Jiaxin Wu , Ting Zhang , Rubing Chen , Wengyu Zhang , Chen Jason Zhang , Xiao-Yong Wei , Li Qing

Motivation: Prediction of ligands for proteins of known 3D structure is important to understand structure-function relationship, predict molecular function, or design new drugs. Results: We explore a new approach for ligand prediction in…

Machine Learning · Statistics 2009-07-10 Brice Hoffmann , Mikhail Zaslavskiy , Jean-Philippe Vert , Véronique Stoven

In drug discovery, molecular dynamics (MD) simulation for protein-ligand binding provides a powerful tool for predicting binding affinities, estimating transport properties, and exploring pocket sites. There has been a long history of…

Traditional drug design faces significant challenges due to inherent chemical and biological complexities, often resulting in high failure rates in clinical trials. Deep learning advancements, particularly generative models, offer potential…

Quantitative Methods · Quantitative Biology 2025-08-27 Mahsa Sheikholeslami , Navid Mazrouei , Yousof Gheisari , Afshin Fasihi , Matin Irajpour , Ali Motahharynia
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