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The study of complex many-body systems via analysis of the trajectories of the units that dynamically move and interact within them is a non-trivial task. The workflow for extracting meaningful information from the raw trajectory data is…

Materials Science · Physics 2025-10-31 Simone Martino , Matteo Becchi , Andrew Tarzia , Daniele Rapetti , Giovanni M. Pavan

High-resolution structural information on membrane proteins is essential for understanding cell biology and for structure-based design of new medical drugs and drug delivery strategies. X-ray diffraction (XRD) can provide {\AA}ngstrom-level…

Biological Physics · Physics 2019-10-29 L. Schmüser , M. Trefz , S. J. Roeters , W. Beckner , J. Pfaendtner , D. Otzen , S. Woutersen , M. Bonn , D. Schneider , T. Weidner

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

Virtual screening of small molecules against protein targets can accelerate drug discovery and development by predicting drug-target interactions (DTIs). However, structure-based methods like molecular docking are too slow to allow for…

In recent years machine learning (ML) took bio- and cheminformatics fields by storm, providing new solutions for a vast repertoire of problems related to protein sequence, structure, and interactions analysis. ML techniques, deep neural…

Biomolecules · Quantitative Biology 2020-03-31 Marta M. Stepniewska-Dziubinska , Piotr Zielenkiewicz , Pawel Siedlecki

The generation of ligands that both are tailored to a given protein pocket and exhibit a range of desired chemical properties is a major challenge in structure-based drug design. Here, we propose an in-silico approach for the $\textit{de…

Biomolecules · Quantitative Biology 2024-05-27 Julian Cremer , Tuan Le , Frank Noé , Djork-Arné Clevert , Kristof T. Schütt

Background and Objective: Deep learning enables tremendous progress in medical image analysis. One driving force of this progress are open-source frameworks like TensorFlow and PyTorch. However, these frameworks rarely address issues…

Image and Video Processing · Electrical Eng. & Systems 2021-04-29 Alain Jungo , Olivier Scheidegger , Mauricio Reyes , Fabian Balsiger

Hydrogen bonds and other non-covalent interactions play a crucial role in maintaining the structural integrity and functionality of biological macromolecules such as proteins and nucleic acids. Accurate identification and analysis of these…

Chemical Physics · Physics 2026-02-23 Abhishek Tiwari

Predicting the binding structure of a small molecule ligand to a protein -- a task known as molecular docking -- is critical to drug design. Recent deep learning methods that treat docking as a regression problem have decreased runtime…

Biomolecules · Quantitative Biology 2023-02-14 Gabriele Corso , Hannes Stärk , Bowen Jing , Regina Barzilay , Tommi Jaakkola

The molecular simulations solve the equation of motion of molecular systems, making 3D shapes of molecules four-dimensional by adding the time coordinate. These methods have a great potential in drug discovery because they can realistically…

Biomolecules · Quantitative Biology 2023-01-19 Dalibor Trapl , Vojtěch Spiwok

Protein-protein interactions (protein functionalities) are mediated by water, which compacts individual proteins and promotes close and temporarily stable large-area protein-protein interfaces. In their classic paper Kyte and Doolittle (KD)…

Soft Condensed Matter · Physics 2009-11-13 Alexander E. Kister , James C. Phillips

Virtual screening (VS) is a critical component of modern drug discovery, yet most existing methods--whether physics-based or deep learning-based--are developed around holo protein structures with known ligand-bound pockets. Consequently,…

Machine Learning · Computer Science 2025-10-31 Wenyu Zhu , Jianhui Wang , Bowen Gao , Yinjun Jia , Haichuan Tan , Ya-Qin Zhang , Wei-Ying Ma , Yanyan Lan

Deep generative models are rapidly advancing structure-based drug design, offering substantial promise for generating small molecule ligands that bind to specific protein targets. However, most current approaches assume a rigid protein…

Biomolecules · Quantitative Biology 2025-11-19 Xinzhe Zheng , Shiyu Jiang , Gustavo Seabra , Chenglong Li , Yanjun Li

Despite the fact that computational fluid dynamics (CFD) software is now (relatively) fast and freely available, it is still amazingly difficult to use. Inaccessible software imposes a significant entry barrier on students and junior…

Computational Physics · Physics 2015-10-26 Gabriel D. Weymouth

Prediction of ligand binding sites of proteins is a fundamental and important task for understanding the function of proteins and screening potential drugs. Most existing methods require experimentally determined protein holo-structures as…

Quantitative Methods · Quantitative Biology 2023-12-07 Shuo Zhang , Lei Xie

Protein-ligand structure prediction is an essential task in drug discovery, predicting the binding interactions between small molecules (ligands) and target proteins (receptors). Recent advances have incorporated deep learning techniques to…

In multi-resolution simulations, different system components are simultaneously modelled at different levels of resolution, these being smoothly coupled together. In the case of enzyme systems, computationally expensive atomistic detail is…

Biological Physics · Physics 2016-11-03 Aoife C. Fogarty , Raffaello Potestio , Kurt Kremer

In drug discovery, structure-based virtual high-throughput screening (vHTS) campaigns aim to identify bioactive ligands or "hits" for therapeutic protein targets from docked poses at specific binding sites. However, while generally…

Quantitative Methods · Quantitative Biology 2021-12-03 Pawel Gniewek , Bradley Worley , Kate Stafford , Henry van den Bedem , Brandon Anderson

Water-phospholipid interactions at the lipid bilayer/water interfaces are of essential importance for the dynamics, stability and function of biological membrane, and are also strongly associated with numerous biological processes at the…

Soft Condensed Matter · Physics 2018-01-04 Jianjun Jiang , Weixin Li , Liang Zhao , Yuanyan Wu , Peng Xiu , Guoning Tang , Yusong Tu

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