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One key task in virtual screening is to accurately predict the binding affinity ($\triangle$$G$) of protein-ligand complexes. Recently, deep learning (DL) has significantly increased the predicting accuracy of scoring functions due to the…

Quantitative Methods · Quantitative Biology 2022-06-28 Zechen Wang , Liangzhen Zheng , Yang Liu , Yuanyuan Qu , Yong-Qiang Li , Mingwen Zhao , Yuguang Mu , Weifeng Li

Prediction of protein-ligand complexes for flexible proteins remains still a challenging problem in computational structural biology and drug design. Here we present two novel deep neural network approaches with significant improvement in…

Biomolecules · Quantitative Biology 2020-08-28 Amr H. Mahmoud , Jonas F. Lill , Markus A. Lill

Molecular docking is a critical computational strategy in drug design and discovery, but the complex diversity of biomolecular structures and flexible binding conformations create an enormous search space that challenges conventional…

Computational Physics · Physics 2025-03-27 Yihan He , Ming-Chun Hong , Qiming Ding , Chih-Sheng Lin , Chih-Ming Lai , Chao Fang , Xiao Gong , Tuo-Hung Hou , Gengchiau Liang

Virtual screening, which identifies potential drugs from vast compound databases to bind with a particular protein pocket, is a critical step in AI-assisted drug discovery. Traditional docking methods are highly time-consuming, and can only…

Machine Learning · Computer Science 2023-10-11 Bowen Gao , Bo Qiang , Haichuan Tan , Minsi Ren , Yinjun Jia , Minsi Lu , Jingjing Liu , Weiying Ma , Yanyan Lan

Deep learning has deeply influenced protein science, enabling breakthroughs in predicting protein properties, higher-order structures, and molecular interactions. This paper introduces DeepProtein, a comprehensive and user-friendly deep…

Machine Learning · Computer Science 2025-06-17 Jiaqing Xie , Tianfan Fu

Motivation. Protein design aims to identify sequences compatible with a given protein fold but incompatible to any alternative folds. To select the correct sequences and to guide the search process, a design scoring function is critically…

Biomolecules · Quantitative Biology 2007-05-23 Changyu Hu , Xiang Li , Jie Liang

SkeleDock is a scaffold docking algorithm which uses the structure of a protein-ligand complex as a template to model the binding mode of a chemically similar system. This algorithm was evaluated in the D3R Grand Challenge 4 pose prediction…

Quantitative Methods · Quantitative Biology 2020-05-13 Alejandro Varela-Rial , Maciej Majewski , Alberto Cuzzolin , Gerard Martínez-Rosell , Gianni De Fabritiis

A central problem in computational biophysics is protein structure prediction, i.e., finding the optimal folding of a given amino acid sequence. This problem has been studied in a classical abstract model, the HP model, where the protein is…

Machine Learning · Computer Science 2023-03-14 Kaiyuan Yang , Houjing Huang , Olafs Vandans , Adithya Murali , Fujia Tian , Roland H. C. Yap , Liang Dai

Accurate prediction of drug-target binding affinity can accelerate drug discovery by prioritizing promising compounds before costly wet-lab screening. While deep learning has advanced this task, most models fuse ligand and protein…

Machine Learning · Computer Science 2025-09-26 Mohammadsaleh Refahi , Bahrad A. Sokhansanj , James R. Brown , Gail Rosen

Proteins play crucial roles in every cellular process by interacting with each other, with nucleic acids, metabolites, and other molecules. The resulting assemblies can be very large and intricate and pose challenges to experimental…

Biomolecules · Quantitative Biology 2021-03-16 Charlotte W. van Noort , Rodrigo V. Honorato , Alexandre M. J. J. Bonvin

Backpropagation (BP) is the standard algorithm for training the deep neural networks that power modern artificial intelligence including large language models. However, BP is energy inefficient and unlikely to be implemented by the brain.…

Machine Learning · Computer Science 2025-10-30 Francesco Innocenti

Computational drug discovery provides an efficient tool helping large scale lead molecules screening. One of the major tasks of lead discovery is identifying molecules with promising binding affinities towards a target, a protein in…

Biological Physics · Physics 2019-09-18 Liangzhen Zheng , Jingrong Fan , Yuguang Mu

Protein-ligand scoring is an important step in a structure-based drug design pipeline. Selecting a correct binding pose and predicting the binding affinity of a protein-ligand complex enables effective virtual screening. Machine learning…

Machine Learning · Statistics 2020-10-19 Joshua Hochuli , Alec Helbling , Tamar Skaist , Matthew Ragoza , David Ryan Koes

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

Proteins are miniature machines whose function depends on their three-dimensional (3D) structure. Determining this structure computationally remains an unsolved grand challenge. A major bottleneck involves selecting the most accurate…

Quantitative Methods · Quantitative Biology 2020-11-30 Stephan Eismann , Patricia Suriana , Bowen Jing , Raphael J. L. Townshend , Ron O. Dror

Molecular docking is an essential tool for drug design. It helps the scientist to rapidly know if two molecules, respectively called ligand and receptor, can be combined together to obtain a stable complex. We propose a new multi-objective…

Quantitative Methods · Quantitative Biology 2008-11-05 Jean-Charles Boisson , Laetitia Jourdan , El-Ghazali Talbi , Dragos Horvath

Empirical scoring functions based on either molecular force fields or cheminformatics descriptors are widely used, in conjunction with molecular docking, during the early stages of drug discovery to predict potency and binding affinity of a…

Machine Learning · Computer Science 2017-03-31 Joseph Gomes , Bharath Ramsundar , Evan N. Feinberg , Vijay S. Pande

Computational protein design has a wide variety of applications. Despite its remarkable success, designing a protein for a given structure and function is still a challenging task. On the other hand, the number of solved protein structures…

Quantitative Methods · Quantitative Biology 2018-04-26 Jingxue Wang , Huali Cao , John Z. H. Zhang , Yifei Qi

Understanding the structure of the protein-ligand complex is crucial to drug development. Existing virtual structure measurement and screening methods are dominated by docking and its derived methods combined with deep learning. However,…

Artificial Intelligence · Computer Science 2024-08-22 Kelei He , Tiejun Dong , Jinhui Wu , Junfeng Zhang

Rising costs in recent years of developing new drugs and treatments have led to extensive research in optimization techniques in biomolecular design. Currently, the most widely used approach in biomolecular design is directed evolution,…

Machine Learning · Computer Science 2021-11-09 Alexander Whatley , Zhekun Luo , Xiangru Tang