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Protein interactions and assembly formation are fundamental to most biological processes. Predicting the assembly structure from constituent proteins -- referred to as the protein docking task -- is thus a crucial step in protein design…

Machine Learning · Computer Science 2023-10-11 Vignesh Ram Somnath , Pier Giuseppe Sessa , Maria Rodriguez Martinez , Andreas Krause

De novo ligand design is a fundamental task that seeks to generate protein or molecule candidates that can effectively dock with protein receptors and achieve strong binding affinity entirely from scratch. It holds paramount significance…

Machine Learning · Computer Science 2025-10-13 Zekai Chen , Xunkai Li , Sirui Zhang , Henan Sun , Jia Li , Zhenjun Li , Bing Zhou , Rong-Hua Li , Guoren Wang

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…

MOTIVATION: Proteins fold into complex structures that are crucial for their biological functions. Experimental determination of protein structures is costly and therefore limited to a small fraction of all known proteins. Hence, different…

Biomolecules · Quantitative Biology 2018-04-18 David Menéndez Hurtado , Karolis Uziela , Arne Elofsson

Molecular docking is a structure-based computational drug design technique for predicting the interaction between a small molecule (ligand) and a macromolecule (receptor). Over the past three decades various docking software programs have…

Quantitative Methods · Quantitative Biology 2023-10-18 Katherine Ge , Dayna Olson , Michel F. Sanner

The paradigm shift toward structure-driven molecule generation has been propelled by advances in deep generative models, such as variational auto-encoders and diffusion models. However, these generative models for molecular design remain…

Machine Learning · Computer Science 2026-04-17 Peidong Liu , Wenbo Zhang , Wei Ju , Jiancheng Lv , Xianggen Liu

Protein design with desirable properties has been a significant challenge for many decades. Generative artificial intelligence is a promising approach and has achieved great success in various protein generation tasks. Notably, diffusion…

Molecular docking aims to predict the 3D pose of a small molecule in a protein binding site. Traditional docking methods predict ligand poses by minimizing a physics-inspired scoring function. Recently, a diffusion model has been proposed…

Quantitative Methods · Quantitative Biology 2023-07-27 Michael Brocidiacono , Konstantin I. Popov , David Ryan Koes , Alexander Tropsha

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

The effects of ligand binding on protein structures and their in vivo functions carry numerous implications for modern biomedical research and biotechnology development efforts such as drug discovery. Although several deep learning (DL)…

Machine Learning · Computer Science 2026-03-24 Alex Morehead , Nabin Giri , Jian Liu , Pawan Neupane , Jianlin Cheng

Simulations of biological macromolecules play an important role in understanding the physical basis of a number of complex processes such as protein folding. Even with increasing computational power and evolution of specialized…

Distributed, Parallel, and Cluster Computing · Computer Science 2019-09-18 Hyungro Lee , Heng Ma , Matteo Turilli , Debsindhu Bhowmik , Shantenu Jha , Arvind Ramanathan

Structure-based drug design (SBDD) aims to generate 3D ligand molecules that bind to specific protein targets. Existing 3D deep generative models including diffusion models have shown great promise for SBDD. However, it is complex to…

Biomolecules · Quantitative Biology 2024-03-01 Zhilin Huang , Ling Yang , Zaixi Zhang , Xiangxin Zhou , Yu Bao , Xiawu Zheng , Yuwei Yang , Yu Wang , Wenming Yang

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

Protein structure prediction and folding are fundamental to understanding biology, with recent deep learning advances reshaping the field. Diffusion-based generative models have revolutionized protein design, enabling the creation of novel…

Machine Learning · Computer Science 2025-10-01 Yogesh Verma , Markus Heinonen , Vikas Garg

In recent years, deep learning techniques have made significant strides in molecular generation for specific targets, driving advancements in drug discovery. However, existing molecular generation methods present significant limitations:…

Machine Learning · Computer Science 2025-03-12 Taojie Kuang , Qianli Ma , Athanasios V. Vasilakos , Yu Wang , Qiang , Cheng , Zhixiang Ren

Proteins are complex biomolecules that perform a variety of crucial functions within living organisms. Designing and generating novel proteins can pave the way for many future synthetic biology applications, including drug discovery.…

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

Generating molecules that bind to specific proteins is an important but challenging task in drug discovery. Previous works usually generate atoms in an auto-regressive way, where element types and 3D coordinates of atoms are generated one…

Biomolecules · Quantitative Biology 2024-07-16 Haitao Lin , Yufei Huang , Odin Zhang , Siqi Ma , Meng Liu , Xuanjing Li , Lirong Wu , Jishui Wang , Tingjun Hou , Stan Z. Li

Powerful generative AI models of protein-ligand structure have recently been proposed, but few of these methods support both flexible protein-ligand docking and affinity estimation. Of those that do, none can directly model multiple binding…

Machine Learning · Computer Science 2025-03-25 Alex Morehead , Jianlin Cheng

Generative modeling has recently undergone remarkable advancements, primarily propelled by the transformative implications of Diffusion Probabilistic Models (DPMs). The impressive capability of these models, however, often entails…

Machine Learning · Computer Science 2023-10-03 Gongfan Fang , Xinyin Ma , Xinchao Wang