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Protein-ligand scoring is a central component of structure-based drug design, underpinning molecular docking, virtual screening, and pose optimization. Conventional physics-based energy functions are often computationally expensive,…

Biomolecules · Quantitative Biology 2026-02-24 Zhangfan Yang , Baoyun Chen , Dong Xu , Jia Wang , Ruibin Bai , Junkai Ji , Zexuan Zhu

Small-molecule foundation models are typically pretrained on standalone molecular data, unlike vision and language models that often benefit from cross-modal or relational supervision. Protein-ligand co-folding provides a molecular analogue…

Biomolecules · Quantitative Biology 2026-05-25 Hyosoon Jang , Hyunjin Seo , Honghui Kim , Seonghyun Park , Taewon Kim , Yunhui Jang , Sungsoo Ahn

Recent developments in surrogate construction predominantly focused on two strategies to improve surrogate accuracy. Firstly, component-wise domain scaling informed by cross-validation. Secondly, regression to construct response surfaces…

Optimization and Control · Mathematics 2023-04-03 Johann Bouwer , Daniel N. Wilke , Schalk Kok

Understanding the mechanisms of shock-induced pore collapse is of great interest in various disciplines in sciences and engineering, including materials science, biological sciences, and geophysics. However, numerical modeling of the…

Computational Physics · Physics 2023-06-05 Siu Wun Cheung , Youngsoo Choi , H. Keo Springer , Teeratorn Kadeethum

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

Molecular docking, a key technique in structure-based drug design, plays pivotal roles in protein-ligand interaction modeling, hit identification and optimization, in which accurate prediction of protein-ligand binding mode is essential.…

Biomolecules · Quantitative Biology 2023-12-20 Jintao Zhu , Zhonghui Gu , Jianfeng Pei , Luhua Lai

Protein-ligand modeling underpins computational drug discovery and molecular design. Existing protein-ligand benchmarks typically evaluate whether a protein and ligand interact and how strongly they bind, through tasks such as binary…

Machine Learning · Computer Science 2026-05-26 Zhaohan Meng , Zhen Bai , Ke Yuan , Iadh Ounis , Zaiqiao Meng , Hao Xu , Joseph Loscalzo

Driven by increased complexity of dynamical systems, the solution of system of differential equations through numerical simulation in optimization problems has become computationally expensive. This paper provides a smart data driven…

Optimization and Control · Mathematics 2021-08-25 Kainat Khowaja , Mykhaylo Shcherbatyy , Wolfgang Karl Härdle

We present TerraBind, a foundation model for protein-ligand structure and binding affinity prediction that achieves 26-fold faster inference than state-of-the-art methods while improving affinity prediction accuracy by $\sim$20\%. Current…

We present results of testing of the ability of eleven popular scoring functions to predict native docked positions using a recently developed method [1] for estimation the entropy contributions of relative motions to protein-ligand binding…

Biological Physics · Physics 2007-05-23 Anatoly M. Ruvinsky

Objective: Deep learning-based deformable image registration has achieved strong accuracy, but remains sensitive to variations in input image characteristics such as artifacts, field-of-view mismatch, or modality difference. We aim to…

Computer Vision and Pattern Recognition · Computer Science 2025-09-15 Yihao Liu , Junyu Chen , Lianrui Zuo , Shuwen Wei , Brian D. Boyd , Carmen Andreescu , Olusola Ajilore , Warren D. Taylor , Aaron Carass , Bennett A. Landman

Current generative models for drug discovery primarily use molecular docking to evaluate the quality of generated compounds. However, such models are often not useful in practice because even compounds with high docking scores do not…

Biomolecules · Quantitative Biology 2024-02-19 Peter Eckmann , Dongxia Wu , Germano Heinzelmann , Michael K Gilson , Rose Yu

This paper introduces a novel two-stage machine learning-based surrogate modeling framework to address inverse problems in scientific and engineering fields. In the first stage of the proposed framework, a machine learning model termed the…

Machine Learning · Computer Science 2024-01-05 Farhad Pourkamali-Anaraki , Jamal F. Husseini , Evan J. Pineda , Brett A. Bednarcyk , Scott E. Stapleton

Protein structure prediction is a core challenge in computational biology, particularly for fragments within ligand-binding regions, where accurate modeling is still difficult. Quantum computing offers a novel first-principles modeling…

Emerging Technologies · Computer Science 2025-08-05 Yuqi Zhang , Yuxin Yang , Cheng-Chang Lu , Weiwen Jiang , Feixiong Cheng , Bo Fang , Qiang Guan

Surrogate models of numerical relativity simulations of merging black holes provide the most accurate tools for gravitational-wave data analysis. Neural network-based surrogates promise evaluation speedups, but their accuracy relies on…

General Relativity and Quantum Cosmology · Physics 2025-05-21 Lucy M. Thomas , Katerina Chatziioannou , Vijay Varma , Scott E. Field

Drug discovery is the most expensive, time demanding and challenging project in biopharmaceutical companies which aims at the identification and optimization of lead compounds from large-sized chemical libraries. The lead compounds should…

Distributed, Parallel, and Cluster Computing · Computer Science 2021-12-02 Natarajan Arul Murugan , Artur Podobas , Davide Gadioli , Emanuele Vitali , Gianluca Palermo , Stefano Markidis

When repeated evaluations for varying parameter configurations of a high-fidelity physical model are required, surrogate modeling techniques based on model order reduction are desired. In absence of the governing equations describing the…

Machine Learning · Computer Science 2023-06-13 Harshit Kapadia , Lihong Feng , Peter Benner

Cardiovascular modeling has rapidly advanced over the past few decades due to the rising needs for health tracking and early detection of cardiovascular diseases. While 1-D arterial models offer an attractive compromise between…

The computational resources required to solve the full 3D inversion of time-domain electromagnetic data are immense. To overcome the time-consuming 3D simulations, we construct a surrogate model, more precisely, a data-driven statistical…

Geophysics · Physics 2024-07-10 Wouter Deleersnyder , David Dudal , Thomas Hermans

Predicting the consensus structure of a set of aligned RNA homologs is a convenient method to find conserved structures in an RNA genome, which has many applications including viral diagnostics and therapeutics. However, the most commonly…

Biomolecules · Quantitative Biology 2024-07-08 Apoorv Malik , Liang Zhang , Milan Gautam , Ning Dai , Sizhen Li , He Zhang , David H. Mathews , Liang Huang
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