AllohubPy: Detecting Allosteric Signals Through An Information-theoretic Approach

作     者：Carmona, Oriol Gracia Kleinjung, Jens Anastasiou, Dimitrios Oostenbrink, Chris Fraternali, Franca 

作者机构：Department of Structural and Molecular Biology Division of Biosciences and Institute of Structural and Molecular Biology University College London London WC1E 6BT United Kingdom Department of Biological Sciences Birkbeck University of London London WC1E 7HX United Kingdom Randall Centre for Cell & Molecular Biosciences King's College London London SE1 1UL United Kingdom Institute for Molecular Modeling and Simulation Department of Material Sciences and Process Engineering BOKU University Vienna 1190 Australia Nxera Pharma Steinmetz & Cori Buildings Granta Park Great Abington Cambridge CB21 6DG United Kingdom Cancer Metabolism Laboratory The Francis Crick Institute 1 Midland Road London NW1 1AT United Kingdom 

出 版 物：《Journal of Molecular Biology》 (J. Mol. Biol.)

年 卷 期：2025年第437卷第15期

页      面：168969页

学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 071010[理学-生物化学与分子生物学] 07[理学] 0703[理学-化学] 

基　　金：Medical Research Council, MRC Cancer Research UK Wellcome Trust UK Medical Research Council Wellcome Trust, WT Cancer Research UK, CRUK, (CC2113) Cancer Research UK, CRUK Biotechnology and Biological Sciences Research Council, BBSRC, (BB/T002212/1) Biotechnology and Biological Sciences Research Council, BBSRC Austrian Science Fund, FWF, (W1224) Austrian Science Fund, FWF 

主　　题：allosteric hubs allostery information theory molecular dynamics mutual information 

摘      要：Allosteric regulation is crucial for biological processes like signal transduction, transcriptional regulation, and metabolism, yet the mechanisms and macromolecular properties that govern it are still not well understood. Several methods have been developed over the years to study allosterism through different angles. Among the possible ways to study allosterism, information-theoretic approaches, like AlloHubMat or GSAtools, can be particularly effective due to their use of robust statistics and the possibility to be combined with graph analysis. These methods capture local conformational changes associated with global motions from molecular dynamics simulations through the use of a Structural Alphabet, which simplifies the complexity of the Cartesian space by reducing the dimensionality down to a string of encoded fragments, representing sets of internal coordinates that still capture the overall conformation changes. In this work, we present “AllohubPy, an improved and standardized methodology of AlloHubMat and GSAtools coded in Python. We analyse the performance, limitations and sampling requirements of AllohubPy by using extensive molecular dynamics simulations of model allosteric systems and apply convergence analysis techniques to estimate result reliability. Additionally, we expand the methodology to use different dimensionality reduction Structural Alphabets, such as the 3DI alphabet, and integrate Protein Language Models (PLMs) to refine allosteric hub communication detection by monitoring the detected evolutionary constraints. Overall, AllohubPy expands its preceding methods and simplifies the use and reliability of the method to effectively capture dynamic allosteric motions and residue pathways. AllohubPy is freely available on GitHub (https://***/Fraternalilab/AlloHubPy) as a package and as a Jupyter Notebook. © 2025 The Author(s)