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To facilitate rational molecular and materials design, this research proposes an integrated computational framework that combines stochastic simulation, ab initio quantum chemistry, and molecular docking. The suggested workflow allows…

Materials Science · Physics 2026-01-08 Md Rakibul Karim Akanda , Michael P. Richard

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

Proteins play a critical role in carrying out biological functions, and their 3D structures are essential in determining their functions. Accurately predicting the conformation of protein side-chains given their backbones is important for…

Quantitative Methods · Quantitative Biology 2024-02-19 Yangtian Zhang , Zuobai Zhang , Bozitao Zhong , Sanchit Misra , Jian Tang

Advances in deep learning have greatly improved structure prediction of molecules. However, many macroscopic observations that are important for real-world applications are not functions of a single molecular structure, but rather…

Existing protein-ligand docking studies typically focus on the self-docking scenario, which is less practical in real applications. Moreover, some studies involve heavy frameworks requiring extensive training, posing challenges for…

Structure-based drug design (SBDD) aims to design small-molecule ligands that bind with high affinity and specificity to pre-determined protein targets. Generative SBDD methods leverage structural data of drugs in complex with their protein…

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

Protein-ligand binding prediction is central to virtual screening and affinity ranking, two fundamental tasks in drug discovery. While recent retrieval-based methods embed ligands and protein pockets into Euclidean space for…

Machine Learning · Computer Science 2025-11-25 Jianhui Wang , Wenyu Zhu , Bowen Gao , Xin Hong , Ya-Qin Zhang , Wei-Ying Ma , Yanyan Lan

Docking is an important tool in computational drug discovery that aims to predict the binding pose of a ligand to a target protein through a combination of pose scoring and optimization. A scoring function that is differentiable with…

Machine Learning · Statistics 2017-10-23 Matthew Ragoza , Lillian Turner , David Ryan Koes

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…

Imitation learning with diffusion models has advanced robotic control by capturing the multi-modal action distributions. However, existing methods typically treat observations only as high-level conditions to the denoising network, rather…

Artificial Intelligence · Computer Science 2026-02-05 Zhaoyang Liu , Mokai Pan , Zhongyi Wang , Kaizhen Zhu , Haotao Lu , Haipeng Zhang , Jingya Wang , Ye Shi

Designing novel proteins that bind to small molecules is a long-standing challenge in computational biology, with applications in developing catalysts, biosensors, and more. Current computational methods rely on the assumption that the…

Biomolecules · Quantitative Biology 2024-09-19 Junqi Liu , Shaoning Li , Chence Shi , Zhi Yang , Jian Tang

We present a computational scheme for predicting the ligands that bind to a pocket of known structure. It is based on the generation of a general abstract representation of the molecules, which is invariant to rotations, translations and…

Chemical Physics · Physics 2024-05-09 R. Beccaria , A. Lazzeri , G. Tiana

Designing novel protein sequences for a desired 3D topological fold is a fundamental yet non-trivial task in protein engineering. Challenges exist due to the complex sequence--fold relationship, as well as the difficulties to capture the…

Machine Learning · Computer Science 2021-06-25 Yue Cao , Payel Das , Vijil Chenthamarakshan , Pin-Yu Chen , Igor Melnyk , Yang Shen

Protein-peptide interactions play essential functional roles in living organisms and their structural characterization is a hot subject of current experimental and theoretical research. Computational modeling of the structure of…

Predicting the binding sites of target proteins plays a fundamental role in drug discovery. Most existing deep-learning methods consider a protein as a 3D image by spatially clustering its atoms into voxels and then feed the voxelized…

Biomolecules · Quantitative Biology 2024-07-24 Yang Zhang , Zhewei Wei , Ye Yuan , Chongxuan Li , Wenbing Huang

Designing protein binders targeting specific sites, which requires to generate realistic and functional interaction patterns, is a fundamental challenge in drug discovery. Current structure-based generative models are limited in generating…

Machine Learning · Computer Science 2025-10-17 Zishen Zhang , Xiangzhe Kong , Wenbing Huang , Yang Liu

Proteolysis targeting chimeras (PROTACs) are small molecules that trigger the breakdown of traditionally ``undruggable'' proteins by binding simultaneously to their targets and degradation-associated proteins. A key challenge in their…

Biomolecules · Quantitative Biology 2024-05-14 Bo Qiang , Wenxian Shi , Yuxuan Song , Menghua Wu

Black-box optimization methods play an important role in many fields of computational simulation. In particular, such methods are often used in the design and modelling of biological systems, including proteins and their complexes with…

Biomolecules · Quantitative Biology 2023-02-08 Dmitry Morozov , Artem Melnikov , Vishal Shete , Michael Perelshtein

Drug discovery is a highly complicated process, and it is unfeasible to fully commit it to the recently developed molecular generation methods. Deep learning-based lead optimization takes expert knowledge as a starting point, learning from…

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