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Simulations are vital for understanding and predicting the evolution of complex molecular systems. However, despite advances in algorithms and special purpose hardware, accessing the timescales necessary to capture the structural evolution…

Computational Physics · Physics 2021-02-18 Pantelis R. Vlachas , Julija Zavadlav , Matej Praprotnik , Petros Koumoutsakos

Modeling the interaction between proteins and ligands and accurately predicting their binding structures is a critical yet challenging task in drug discovery. Recent advancements in deep learning have shown promise in addressing this…

Machine Learning · Computer Science 2024-01-10 Qizhi Pei , Kaiyuan Gao , Lijun Wu , Jinhua Zhu , Yingce Xia , Shufang Xie , Tao Qin , Kun He , Tie-Yan Liu , Rui Yan

In cancer therapeutics, protein-metal binding mechanisms critically govern the pharmacokinetics and targeting efficacy of drugs, thereby fundamentally shaping the rational design of anticancer metallodrugs. While conventional laboratory…

Simulating physical systems is a core component of scientific computing, encompassing a wide range of physical domains and applications. Recently, there has been a surge in data-driven methods to complement traditional numerical simulations…

Machine Learning · Computer Science 2021-08-19 Karl Otness , Arvi Gjoka , Joan Bruna , Daniele Panozzo , Benjamin Peherstorfer , Teseo Schneider , Denis Zorin

The discovery of novel drug target (DT) interactions is an important step in the drug development process. The majority of computer techniques for predicting DT interactions have focused on binary classification, with the goal of…

Machine Learning · Computer Science 2023-03-22 Partho Ghosh , Md. Aynal Haque

Recent advancements in structure-based drug design (SBDD) have significantly enhanced the efficiency and precision of drug discovery by generating molecules tailored to bind specific protein pockets. Despite these technological strides,…

Biomolecules · Quantitative Biology 2024-06-14 Bowen Gao , Haichuan Tan , Yanwen Huang , Minsi Ren , Xiao Huang , Wei-Ying Ma , Ya-Qin Zhang , Yanyan Lan

Molecular simulations can provide microscopic insight into the physical and chemical driving forces of complex molecular processes. Despite continued advancement of simulation methodology, model errors may lead to inconsistencies between…

Chemical Physics · Physics 2016-02-12 Joseph F. Rudzinski , Kurt Kremer , Tristan Bereau

The field of machine learning for drug discovery is witnessing an explosion of novel methods. These methods are often benchmarked on simple physicochemical properties such as solubility or general druglikeness, which can be readily…

Publicly available collections of drug-like molecules have grown to comprise 10s of billions of possibilities in recent history due to advances in chemical synthesis. Traditional methods for identifying "hit" molecules from a large…

Targeting RNA with small molecules offers significant therapeutic potential. Machine learning could substantially accelerate preclinical drug discovery, from hit identification to lead optimization. Yet a fundamental limitation emerges:…

Biomolecules · Quantitative Biology 2025-12-18 Wissam Karroucha , Carlos Oliver , Veronique Stoven , Vincent Mallet

The most important factor for quantitative results in molecular dynamics simulation are well developed force fields and models. In the present work, the development of new models and the usage of force fields from the literature in large…

Computational Physics · Physics 2010-05-25 Jonathan Walter , Thorsten Merker , Martin Horsch , Jadran Vrabec , Hans Hasse

We present a novel machine learning approach to understanding conformation dynamics of biomolecules. The approach combines kernel-based techniques that are popular in the machine learning community with transfer operator theory for…

Computational Physics · Physics 2019-01-24 Stefan Klus , Andreas Bittracher , Ingmar Schuster , Christof Schütte

The keyboard design is a novel phase I dose-finding method that is simple and has good operating characteristics. This paper studies theoretical properties of the keyboard design, including the optimality of its decision rules, coherence in…

Methodology · Statistics 2017-12-20 Haitao Pan , Ruitao Lin , Ying Yuan

We evaluate the feasibility of using co-folding models for synthetic data augmentation in training machine learning-based scoring functions (MLSFs) for binding affinity prediction. Our results show that performance gains depend critically…

Machine Learning · Computer Science 2025-07-11 Wei-Tse Hsu , Savva Grevtsev , Thomas Douglas , Aniket Magarkar , Philip C. Biggin

Accurate prediction of protein-ligand binding affinity is crucial for rapid and efficient drug development. Recently, the importance of predicting binding affinity has led to increased attention on research that models the three-dimensional…

Machine Learning · Computer Science 2024-07-17 Seungyeon Choi , Sangmin Seo , Sanghyun Park

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

Computational methods are useful in accelerating the pace of drug discovery. Drug discovery carries several steps such as target identification and validation, lead discovery, and lead optimisation etc., In the phase of lead optimisation,…

Machine Learning · Computer Science 2024-08-31 K. Venkateswara Rao , Kunjam Nageswara Rao , G. Sita Ratnam

An exactly solvable model based on the topology of a protein native state is applied to identify bottlenecks and key-sites for the folding of HIV-1 Protease. The predicted sites are found to correlate well with clinical data on resistance…

Statistical Mechanics · Physics 2007-05-23 Cristian Micheletti , Fabio Cecconi , Alessandro Flammini , Amos Maritan

Resistance to chemotherapy and molecularly targeted therapies is a major factor in limiting the effectiveness of cancer treatment. In many cases, resistance can be linked to genetic changes in target proteins, either pre-existing or…

Distributed, Parallel, and Cluster Computing · Computer Science 2018-02-15 Jumana Dakka , Matteo Turilli , David W Wright , Stefan J Zasada , Vivek Balasubramanian , Shunzhou Wan , Peter V Coveney , Shantenu Jha

Molecular dynamics (MD) has become a powerful tool for studying biophysical systems, due to increasing computational power and availability of software. Although MD has made many contributions to better understanding these complex…

Computational Physics · Physics 2019-09-27 Yihang Wang , Joao Marcelo Lamim Ribeiro , Pratyush Tiwary