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Prediction models based on deep neural networks are increasingly gaining attention for fast and accurate virtual screening systems. For decision makings in virtual screening, researchers find it useful to interpret an output of…

Machine Learning · Computer Science 2020-03-18 Soojung Yang , Kyung Hoon Lee , Seongok Ryu

Understanding how proteins structurally interact is crucial to modern biology, with applications in drug discovery and protein design. Recent machine learning methods have formulated protein-small molecule docking as a generative problem…

We introduce Compositional Imitation Learning and Execution (CompILE): a framework for learning reusable, variable-length segments of hierarchically-structured behavior from demonstration data. CompILE uses a novel unsupervised,…

Virtual screening (VS) is an essential technique for understanding biomolecular interactions, particularly, drug design and discovery. The best-performing VS models depend vitally on three-dimensional (3D) structures, which are not…

Biomolecules · Quantitative Biology 2022-12-29 Li Shen , Hongsong Feng , Yuchi Qiu , Guo-Wei Wei

Small molecule drug design hinges on obtaining co-crystallized ligand-protein structures. Despite AlphaFold2's strides in protein native structure prediction, its focus on apo structures overlooks ligands and associated holo structures.…

Biological Physics · Physics 2024-07-08 Xinyu Gu , Akashnathan Aranganathan , Pratyush Tiwary

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

Mechanistic dynamic models of biochemical networks such as Ordinary Differential Equations (ODEs) contain unknown parameters like the reaction rate constants and the initial concentrations of the compounds. The large number of parameters as…

Data Analysis, Statistics and Probability · Physics 2017-08-14 Clemens Kreutz , Andreas Raue , Jens Timmer

We demonstrate a machine learning based approach which can learn the time-dependent electronic excitation dynamics of small molecules subjected to ion irradiation. Ensembles of recurrent neural networks are trained on data generated by…

Chemical Physics · Physics 2024-09-24 Ethan P. Shapera , Cheng-Wei Lee

Computational protein structure determination involves optimization in a problem space much too large to exhaustively search. Existing approaches include optimization algorithms such as gradient descent and simulated annealing, but these…

Distributed, Parallel, and Cluster Computing · Computer Science 2020-08-04 Michael Bryson , Xijiang Miao , Homayoun Valafar

Shape-based virtual screening is widely employed in ligand-based drug design to search chemical libraries for molecules with similar 3D shapes yet novel 2D chemical structures compared to known ligands. 3D deep generative models have the…

Chemical Physics · Physics 2022-10-12 Keir Adams , Connor W. Coley

Molecular dynamics simulations are used to study structure formation in simple model polymer chains that are subject to excluded volume and torsional interactions. The changing conformations exhibited by chains of different lengths under…

Soft Condensed Matter · Physics 2009-11-07 D. C. Rapaport

Understanding the dynamic behavior of proteins is critical to elucidating their functional mechanisms, yet generating realistic, temporally coherent trajectories of protein ensembles remains a significant challenge. In this work, we…

Biomolecules · Quantitative Biology 2025-11-11 Yaoyao Xu , Di Wang , Zihan Zhou , Tianshu Yu , Mingchen Chen

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

Most widely used ligand docking methods assume a rigid protein structure. This leads to problems when the structure of the target protein deforms upon ligand binding. In particular, the ligand's true binding pose is often scored very…

Biomolecules · Quantitative Biology 2023-03-22 Patricia Suriana , Joseph M. Paggi , Ron O. Dror

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…

We develop an online optimisation algorithm for in situ calibration of collision models in simulations of rarefied gas flows. The online optimised collision models are able to achieve similar accuracy to Direct Molecular Simulation (DMS) at…

Fluid Dynamics · Physics 2024-11-21 Nicholas Daultry Ball , Jonathan F. MacArt , Justin Sirignano

Disordered proteins play essential roles in myriad cellular processes, yet their structural characterization remains a major challenge due to their dynamic and heterogeneous nature. We here present a community-driven initiative to address…

We develop a systematic approach for surrogate model construction in reduced input parameter spaces. A sparse set of model evaluations in the original input space is used to approximate derivative based global sensitivity measures (DGSMs)…

Applications · Statistics 2018-06-19 Manav Vohra , Alen Alexanderian , Cosmin Safta , Sankaran Mahadevan

De novo molecular design has facilitated the exploration of large chemical space to accelerate drug discovery. Structure-based de novo method can overcome the data scarcity of active ligands by incorporating drug-target interaction into…

Biomolecules · Quantitative Biology 2022-09-16 Yaqin Li , Lingli Li , Yongjin Xu , Yi Yu

Molecular docking, given a ligand molecule and a ligand binding site (called ``pocket'') on a protein, predicting the binding mode of the protein-ligand complex, is a widely used technique in drug design. Many deep learning models have been…

Biomolecules · Quantitative Biology 2023-02-24 Yuejiang Yu , Shuqi Lu , Zhifeng Gao , Hang Zheng , Guolin Ke