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Binding kinetic parameters can be correlated with drug efficacy, which led to the development of various computational methods for predicting binding kinetic rates and gaining insight into protein-drug binding paths and mechanisms in recent…

Biomolecules · Quantitative Biology 2022-09-27 Farzin Sohraby , Ariane Nunes-Alves

We consider two minimal mathematical models for cancer dynamics and self-adaptation. We aim to capture the interplay between the rapid progression of cancer growth and the possibility to leverage and enhance self-adaptive defense mechanisms…

Adaptation and Self-Organizing Systems · Physics 2025-03-27 Christian Kuehn

Drug target binding affinity (DTA) is a key criterion for drug screening. Existing experimental methods are time-consuming and rely on limited structural and domain information. While learning-based methods can model sequence and structural…

Machine Learning · Computer Science 2024-06-26 Xi Xiao , Wentao Wang , Jiacheng Xie , Lijing Zhu , Gaofei Chen , Zhengji Li , Tianyang Wang , Min Xu

The identification of novel drug-target (DT) interactions is a substantial part of the drug discovery process. Most of the computational methods that have been proposed to predict DT interactions have focused on binary classification, where…

Machine Learning · Statistics 2019-02-06 Hakime Öztürk , Elif Ozkirimli , Arzucan Özgür

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

Free-energy-based adaptive biasing methods, such as Metadynamics, the Adaptive Biasing Force (ABF) and their variants, are enhanced sampling algorithms widely used in molecular simulations. Although their efficiency has been empirically…

Probability · Mathematics 2026-01-29 Tony Lelièvre , Xuyang Lin , Pierre Monmarché

Recent clinical trials have shown that the adaptive drug therapy can be more efficient than a standard MTD-based policy in treatment of cancer patients. The adaptive therapy paradigm is not based on a preset schedule; instead, the doses are…

Quantitative Methods · Quantitative Biology 2020-08-06 Mark Gluzman , Jacob G. Scott , Alexander Vladimirsky

The first step in drug discovery is finding drug molecule moieties with medicinal activity against specific targets. Therefore, it is crucial to investigate the interaction between drug-target proteins and small chemical molecules. However,…

Biomolecules · Quantitative Biology 2022-11-15 Boyuan Liu

Molecular dynamics (MD) simulations are useful in obtaining thermodynamic and kinetic properties of bio-molecules but are limited by the timescale barrier, i.e., we may be unable to efficiently obtain properties because we need to run…

Chemical Physics · Physics 2017-08-23 Surl-Hee Ahn , Jay W. Grate , Eric F. Darve

Compound-protein pairs dominate FDA-approved drug-target pairs and the prediction of compound-protein affinity and contact (CPAC) could help accelerate drug discovery. In this study we consider proteins as multi-modal data including 1D…

Biomolecules · Quantitative Biology 2020-12-02 Yuning You , Yang Shen

The ability to predict accurate thermodynamic and kinetic properties in biomolecular systems is of both scientific and practical utility. While both remain very difficult, predictions of kinetics are particularly difficult because rates, in…

Chemical Physics · Physics 2018-06-13 Yong Wang , Omar Valsson , Pratyush Tiwary , Michele Parrinello , Kresten Lindorff-Larsen

Despite recent advances in protein-ligand structure prediction, deep learning methods remain limited in their ability to accurately predict binding affinities, particularly for novel protein targets dissimilar from the training set. In…

Quantitative Methods · Quantitative Biology 2025-12-04 Michael Brocidiacono , James Wellnitz , Konstantin I. Popov , Alexander Tropsha

Computational models and simulations are not just appealing because of their intrinsic characteristics across spatiotemporal scales, scalability, and predictive power, but also because the set of problems in cancer biomedicine that can be…

Tissues and Organs · Quantitative Biology 2023-11-01 Nicolò Cogno , Cristian Axenie , Roman Bauer , Vasileios Vavourakis

Free energy perturbation (FEP) is considered the gold-standard simulation method for estimating small molecule binding affinity, a quantity of vital importance to drug discovery. The accuracy of FEP critically depends on an accurate model…

We provide an overview of the successive steps that made possible to obtain increasingly accurate excitation energies with computational chemistry tools, eventually leading to chemically accurate vertical transition energies for small- and…

Chemical Physics · Physics 2020-06-05 Pierre-François Loos , Anthony Scemama , Denis Jacquemin

This letter gives results on improving protein-ligand binding affinity predictions based on molecular dynamics simulations using machine learning potentials with a hybrid neural network potential and molecular mechanics methodology…

Hybrid controlled trials (HCTs), which augment randomized controlled trials (RCTs) with external controls (ECs), are increasingly receiving attention as a way to address limited power, slow accrual, and ethical concerns in clinical…

Methodology · Statistics 2025-05-02 Jiajun Liu , Ke Zhu , Shu Yang , Xiaofei Wang

Recent developments dedicated to the building of multiscale mechanical and chemical constitutive laws for energetic molecular crystals are presented and discussed. In particular, various tools have been specifically incorporated in…

Mesoscale and Nanoscale Physics · Physics 2025-08-05 Paul Lafourcade , Nicolas Bruzy , Paul Bouteiller , Jean-Bernard Maillet , Christophe Denoual

One of the main goals of sequential, multiple assignment, randomized trials (SMART) is to find the most efficacious design embedded dynamic treatment regimes. The analysis method known as multiple comparisons with the best (MCB) allows…

Methodology · Statistics 2020-08-07 William J. Artman , Ashkan Ertefaie , Kevin G. Lynch , James R. McKay

Likelihood-free Bayesian inference algorithms are popular methods for calibrating the parameters of complex, stochastic models, required when the likelihood of the observed data is intractable. These algorithms characteristically rely…

Computation · Statistics 2021-12-23 Thomas P Prescott , David J Warne , Ruth E Baker