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Simulating drug binding and unbinding is a challenge, as the rugged energy landscapes that separate bound and unbound states require extensive sampling that consumes significant computational resources. Here, we describe the use of…

Despite improved rational drug design and a remarkable progress in genomic, proteomic and high-throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade. Multi-target drugs…

Molecular Networks · Quantitative Biology 2007-05-23 Tamas Korcsmaros , Mate S. Szalay , Csaba Bode , Istvan A. Kovacs , Peter Csermely

Cells use surface receptors to estimate the concentration of external ligands. Limits on the accuracy of such estimations have been well studied for pairs of ligand and receptor species. However, the environment typically contains many…

Molecular Networks · Quantitative Biology 2015-06-02 Vijay Singh , Ilya Nemenman

Understanding the binding dynamics of liquid molecules is of fundamental importance in physical and life sciences. However, nanoscale fast dynamics pose great challenges for experimental characterization. Conventionally, the binding…

Chemical Physics · Physics 2024-10-28 Shiyi Qin , Zhi Yang , Huimin Liu , Xiaoli Wang , Shangguo Hou , Kai Huang

Currently, the field of structure-based drug design is dominated by three main types of algorithms: search-based algorithms, deep generative models, and reinforcement learning. While existing works have typically focused on comparing models…

Machine Learning · Computer Science 2024-06-06 Kangyu Zheng , Yingzhou Lu , Zaixi Zhang , Zhongwei Wan , Yao Ma , Marinka Zitnik , Tianfan Fu

Aligning theoretical atomistic structural models of materials with available experimental data presents a significant challenge for disordered systems. The configurational space to navigate is vast, and faithful realizations require large…

Materials Science · Physics 2025-09-29 Tigany Zarrouk , Miguel A. Caro

Design of new drugs is a challenging process: a candidate molecule should satisfy multiple conditions to act properly and make the least side-effect -- perfect candidates selectively attach to and influence only targets, leaving off-targets…

Biomolecules · Quantitative Biology 2024-05-07 Andrij Rovenchak , Maksym Druchok

Multivalent binding employs multiple simultaneous supramolecular interactions, increasing avidity and selectivity compared with monovalent binding. While equilibrium aspects of multivalency are well characterized, non-equilibrium behavior…

Soft Condensed Matter · Physics 2026-05-27 Vid Ravnik , Baptiste Chabaud , Urban Bren , Galina V. Dubacheva , Tine Curk

We present an efficient approach to precisely simulate tight binding models with optical lattices, based on programmable digital-micromirror-device (DMD) techniques. Our approach consists of a subroutine of Wegner-flow enabled precise…

Quantum Gases · Physics 2020-10-20 Xingze Qiu , Jie Zou , Xiaodong Qi , Xiaopeng Li

The estimation of uncertainties associated with predictions from quantitative structure-activity relationship (QSAR) models can accelerate the drug discovery process by identifying promising experiments and allowing an efficient allocation…

Machine Learning · Computer Science 2025-02-07 Hannah Rosa Friesacher , Emma Svensson , Susanne Winiwarter , Lewis Mervin , Adam Arany , Ola Engkvist

Molecular dynamics (MD) simulations are essential tools in computational chemistry and drug discovery, offering crucial insights into dynamic molecular behavior. However, their utility is significantly limited by substantial computational…

Chemical Physics · Physics 2025-09-04 Bin Feng , Jiying Zhang , Xinni Zhang , Zijing Liu , Yu Li

Molecular Dynamics (MD) simulations are fundamental computational tools for the study of proteins and their free energy landscapes. However, sampling protein conformational changes through MD simulations is challenging due to the relatively…

Biomolecules · Quantitative Biology 2023-07-20 Diego E. Kleiman , Hassan Nadeem , Diwakar Shukla

The last decade has witnessed a swiftly increasing interest in the design and production of novel multivalent molecules as powerful alternatives for conventional antibodies in the fight against cancer and infectious diseases. However, while…

Soft Condensed Matter · Physics 2019-08-23 Suman Saurabh , Francesco Piazza

Molecular dynamics simulations have been performed on pure liquid water, aqueous solutions of sodium chloride, and polymer solutions exposed to a strong external electric field with the goal to gain molecular insight into the structural…

Soft Condensed Matter · Physics 2016-08-08 I. Nezbeda , J. Jirsák , F. Moučka , W. R. Smith

Developing and discovering new drugs is a complex and resource-intensive endeavor that often involves substantial costs, time investment, and safety concerns. A key aspect of drug discovery involves identifying novel drug-target (DT)…

Machine Learning · Computer Science 2024-02-13 Rakesh Bal , Yijia Xiao , Wei Wang

Structure-based drug design (SBDD), which aims to generate 3D ligand molecules binding to target proteins, is a fundamental task in drug discovery. Existing SBDD methods typically treat protein as rigid and neglect protein structural change…

Biomolecules · Quantitative Biology 2024-10-01 Zaixi Zhang , Mengdi Wang , Qi Liu

In recent years, machine learning (ML) methods have emerged as promising alternatives for molecular docking, offering the potential for high accuracy without incurring prohibitive computational costs. However, recent studies have indicated…

Biomolecules · Quantitative Biology 2024-05-21 Eric Alcaide , Zhifeng Gao , Guolin Ke , Yaqi Li , Linfeng Zhang , Hang Zheng , Gengmo Zhou

Molecular dynamics simulations use statistical mechanics at the atomistic scale to enable both the elucidation of fundamental mechanisms and the engineering of matter for desired tasks. The behavior of molecular systems at the microscale is…

Computational Physics · Physics 2020-12-25 Wujie Wang , Simon Axelrod , Rafael Gómez-Bombarelli

Virtual screening of large compound libraries to identify potential hit candidates is one of the earliest steps in drug discovery. As the size of commercially available compound collections grows exponentially to the scale of billions,…

Machine Learning · Computer Science 2023-09-22 Zhonglin Cao , Simone Sciabola , Ye Wang

The adhesion of biological membranes is mediated by the binding of membrane-anchored receptor and ligand proteins. Central questions are how the binding kinetics of these proteins is affected by the membranes and by the membrane anchoring…

Biomolecules · Quantitative Biology 2015-11-30 Jinglei Hu , Guang-Kui Xu , Reinhard Lipowsky , Thomas R. Weikl